This study assesses the relevance of questions for the new breast reconstruction questionnaire evaluating patients’ health related quality of life. The provisional 31-item questionnaire was developed according to composite EORTC quality of life group guidelines. Ethical approval was obtained from participating centres in 5 countries. Patients who underwent prophylactic mastectomy were excluded from the study. Patients were categorised into prospective and retrospective groups. The former (n=47) completed the provisional questionnaire which included presurgical questionnaire as well as postsurgical questionnaire at 3 months after definitive reconstruction. The latter group (n=150) were within 1-5 years after definitive reconstruction. Patients scored each item on a four-point scale, rating each for ‘relevance’ and ‘difficulty’, as ‘yes’ or ‘no’. Patients were also asked to list five priority items. The questionnaire consisted of items on surgery, body image, sexuality, cosmetic outcomes, and overall satisfaction. Two thirds of breast reconstruction was performed immediately and tissue-based procedures were performed in 70.4%. All items fulfilled ‘relevance’ with none producing ‘difficulties’. Ten items were not a priority for 10% of the respondents. Three redundant items were deleted; arm weakness, and shape and colour of affected nipple. This resulted in a new questionnaire EORTC QLQ-BRR26 which has 26 items in three provisional scales (disease treatment/surgery, sexuality and cosmetic outcomes).
British Journal of Surgery 2014; DOI; 10.1002/bjs.9397
This Spanish Breast Cancer Research Group (GEICAM) study is a prospective, observational study to examine the conversion rate of receptor status (ER, PR, and HER2) between primary tumour and recurrent tumours. The receptor status determination was carried out in a central laboratory in a blinded manner. The study was carried out in 31 centres and patients with a suspected diagnosis of local recurrence or distant metastasis was identified between 2009 to 2011 (n=178). Patients required FFPE tissue samples from the primary tumours and were required to undergo a biopsy of the recurrence within 6 weeks of the identification of suspected recurrence. In the central laboratory, tumours with moderate-to-intense nuclear staining of ≥1% or an Allred score of ≥3 were considered ER or PR positive. HER2 expression was scored as negative (0,1+), indeterminate (2+), or positive (3+). In cases of indeterminate expression or discordance between primary and metastatic tumour, FISH was carried out. Local protocols varied in each institution. The conversion rate for HER2 was 16%, with 10% gain and 6% loss of expression. For ER the conversion rate was 21%, with 12% gain and 9% loss of expression. The conversion rate of PR was 35%, with 13% gain and 22% loss of expression. Overall conversion rate was 15% for the hormone receptors, equally distributed for gain or loss of expression. Hormone receptor discordance was only seen in 1/15 patients (7%) with triple-negative subtype. In 26%, the subtype between the primary tumour and metastatic lesion changed with most frequent change being from hormone receptor positive to HER2-amplified tumours. Other frequent change was from hormone receptor positive to triple-negative tumours. There was good agreement between local and central laboratory for HER2 expression and for ER expression (kappa index=0.794), but not for PR expression (kappa index=0.555).The intended treatment plan changed in 15 patients (8%) after the biopsy.
Breast Cancer Research and Treatment 2014; DOI; 10.1007/s10549-013-2825-2
This study evaluates the use of blue dye alone to identify sentinel lymph node (SLN) in a single institution involving 4 accredited breast surgeons. Between 2001-2005, SLN biopsies (n=170) were carried out selectively using blue dye only, and always followed by axillary lymph node dissection (ALND). Between 2006-2010, SLN biopsies (n=610) were performed with blue dye only, and ALND only performed when SLN was not identified or involved by metastasis. 170/191 SLN biopsies were performed in the former period using blue dye only. The overall SLN non-identification rate was 8.4% (16/191), and all 16 cases occurred amongst the patients who received blue dye only. This resulted in a non-identification rate in the blue dye only group of 9.4%. The overall false-negative rate was 31% (21/68). The median number of SLN identified was 1 with a mean of 2, and a single SLN was identified in 81/154 patients (52.6%). In the latter period, SLN identification rate was 98% (598/610). The median number of SLN identified was 2 with a mean of 2.5, and a single SLN was identified in 227/598 patients (38%). SLN was not identified in 12 patients only where only one had involved nodes. Metastatic disease was found in 128/598 patients (21.4%). OF 470 patients with a negative SLN biopsy, metastasis was found in 2 patients in the axillary tail of the mastectomy specimen. In the latter period ipsilateral axillary nodal recurrence occurred in one patient, and in the former period ipsilateral axillary nodal recurrence occurred in one patient also. Over 10 years, 2 patients developed urticarial with no systemic symptoms, and 1 patient developed anaphylaxis.
British Journal of Surgery 2014; DOI; 10.1002/bjs.9390
Anthracyclines and taxanes have been the standard neoadjuvant chemotherapies for breast cancer in the past decade. This study aimed to assess safety and efficacy of the addition of gemcitabine to accelerated paclitaxel with epirubicin and cyclophosphamide, and also the effect of sequencing the blocks of epirubicin and cyclophosphamide and paclitaxel (with or without gemcitabine. This randomised, open-label, 2×2 factorial phase 3 trial (Neo-tAnGo), authors enrolled women (aged >18 years) with newly diagnosed breast cancer (tumour size >20 mm) at 57 centres in the UK. Patients were randomly assigned to epirubicin and cyclophosphamide then paclitaxel (with or without gemcitabine) or paclitaxel (with or without gemcitabine) then epirubicin and cyclophosphamide. Four cycles of each component were given. The primary endpoint was pathological complete response (pCR), defined as absence of invasive cancer in the breast and axillary lymph nodes. Study randomly allocated 831 participants; 207 received epirubicin and cyclophosphamide then paclitaxel; 208 were given paclitaxel then epirubicin and cyclophosphamide; 208 had epirubicin and cyclophosphamide followed by paclitaxel and gemcitabine; and 208 received paclitaxel and gemcitabine then epirubicin and cyclophosphamide. Median follow-up was 47 months (IQR 37—51). 207 (25%) patients had inflammatory or locally advanced disease, 169 (20%) patients had tumours larger than 50 mm, 413 (50%) patients had clinical involvement of axillary nodes, 276 (33%) patients had oestrogen receptor (ER)-negative disease, and 191 (27%) patients had HER2-positive disease. Addition of gemcitabine did not increase pCR: 70 (17%, 95% CI 14—21) of 404 patients in the epirubicin and cyclophosphamide then paclitaxel group achieved pCR compared with 71 (17%, 14—21) of 408 patients who received additional gemcitabine (p=0•98). Receipt of a taxane before anthracycline was associated with improved pCR: 82 (20%, 95% CI 16—24) of 406 patients who received paclitaxel with or without gemcitabine followed by epirubicin and cyclophosphamide achieved pCR compared with 59 (15%, 11—18) of 406 patients who received epirubicin and cyclophosphamide first (p=0•03). Grade 3 toxicities were reported at expected levels: 173 (21%) of 812 patients who received treatment and had full treatment details had grade 3 neutropenia, 66 (8%) had infection, 41 (5%) had fatigue, 41 (5%) had muscle and joint pains, 37 (5%) had nausea, 36 (4%) had vomiting, 34 (4%) had neuropathy, 23 (3%) had transaminitis, 16 (2%) had acute hypersensitivity, and 20 (2%) had a rash. 86 (11%) patients had grade 4 neutropenia and 3 (<1%) had grade 4 infection.
Lancet Oncology 2014; doi: doi:10.1016/S1470-2045(13)70554-0
Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in a retrospective review of screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories. This study included 2,245 invasive tumors (1,297 screen-detected and 948 interval cancers) diagnosed from 2000-2009 among 645,764 women aged 45-69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review of screening and diagnostic mammograms into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd's scale and was conflated into: <25%; 25-50%; 50-75%; >75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER+/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2-. Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes [OR = 1.91 (95%CI:1.22-2.96), OR = 2.07 (95%CI:1.42-3.01), respectively] and extremely dense breasts (>75%) [OR = 1.67 (95%CI:1.08-2.56)]. However, among true interval cancers the highest proportion of triple-negative tumors was observed in predominantly fatty breasts (<25%) than in denser breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively;<0.001). False-negatives and occult tumors had similar phenotypic characteristics to screen-detected cancers, extreme breast density being strongly associated with occult tumors [OR = 6.23 (95%CI:2.65-14.66)]. Minimal-sign cancers were biologically close to true interval cancers but showed no association with breast density.
Breast Cancer Research 2014; doi: doi:10.1186/bcr3595
The rate of bilateral mastectomy and bilateral breast reconstruction is increasing. The DIEP flap is an ideal method of breast reconstruction. The difference in risk of adverse outcomes between unilateral and bilateral DIEP flap breast reconstruction is unclear. The aim of this review is to investigate this relationship. Authors searched Ovid EMBASE and MEDLINE from database inception to March 2012, for reports of DIEP flap breast reconstruction studies. After screening, data were extracted on flap-related, donor-site and systemic adverse events. Authors performed meta-analysis of direct comparisons to generate relative risk (RR) ratios with 95% confidence intervals (CI) using a random-effects model. Overall, 17 case-series of 2398 women were included. Compared with unilateral DIEP flap breast reconstruction, bilateral reconstruction was associated with a significantly higher risk of total flap failure (RR 3.31 [95% CI 1.50–7.28]; p = 0.003) and breast seroma (RR 7.15 [95% CI 1.21–42.36]; p = 0.03). Differences between other outcomes were non-significant, although descriptive analysis appeared to favour unilateral reconstruction.
Journal of Plastic, Reconstructive & Aesthetic Surgery 2014; doi:0.1016/j.bjps.2013.10.024
Acellular dermal matrix has been used for over a decade in primary breast reconstruction. Few articles have specifically examined its use in revision breast reconstruction for fold malposition, capsular contracture, rippling, and symmastia. One hundred thirty-five revision breast reconstructive procedures using acellular dermal matrix (AlloDerm) in 118 patients (154 breasts) over a 5-year period were reviewed. Most procedures were revisions or part of the second stage of previous mastectomy reconstructions; three were revisions after reconstruction of congenital chest wall deformities. Fifty-seven revisions (37 percent) were for inferior fold malposition, followed by 40 (25.9 percent) for inferior pole support, 42 (27.2 percent) for capsular contracture, 10 (6.4 percent) for rippling, and five (3.2 percent) for symmastia. The overall complication rate was 5 percent. Revisions with acellular dermal matrix were successful in 147 of 154 breasts (95.5 percent). The most common complication was capsular contracture, occurring in five breasts (3.2 percent). There was one infection (0.6 percent), failure to lower the inframammary fold in one breast (0.6 percent), and one persistence of rippling (0.6 percent). The mean follow-up was 207 days.
Plastic and Reconstructive Surgery 2014; doi: 10.1097/01.prs.0000436810.88659.36
The authors have developed a simple and intuitive method for measuring breast volume based on three-dimensional simulated images of magnetic resonance imaging scans to accurately estimate breast volume before breast reconstruction.The authors performed a retrospective review of the medical records of 18 patients (20 breasts) who had undergone breast reconstruction at Yeouido St. Mary’s Hospital. All of the patients underwent preoperative assessment of breast volume with two methods: a plaster cast maneuver and a three-dimensional simulated magnetic resonance imaging scan. To determine the accuracy of each method, the authors compared the mastectomy volume with the plaster cast maneuver and with three-dimensional simulated magnetic resonance imaging.In the authors’ series, the mean values of the plaster cast maneuver, three-dimensional simulated magnetic resonance imaging, and mastectomy volume were 433.85 ± 176.65 ml, 529 ± 193.33 ml, and 495.25 ± 192.45 ml, respectively. In addition, the mean error between the plaster cast maneuver and mastectomy volume was 137.4 ± 97.66 ml and that between three-dimensional simulated magnetic resonance imaging and mastectomy volume was 54.63 ± 46.30 ml. From a linear regression curve, the correlation coefficient (r2) of the plaster cast maneuver was 0.629 (p = 0.003) and that of three-dimensional simulated magnetic resonance imaging was 0.945 (p < 0.001).
Plastic and Reconstructive surgery 2014; doi: 10.1097/01.prs.0000436813.03838.09
Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. Authors aimed to establish whether adjuvant chemotherapy improves the outcome of such patients. The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival. 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6—6 ·0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56—79) with chemotherapy versus 57% (44—67) without chemotherapy (hazard ratio 0·59 [95% CI 0·35—0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (pinteraction=0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant. Of the 81 patients who received chemotherapy, 12 (15%) had serious adverse events. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection.
The Lancet Oncology 2014; doi:10.1016/S1470-2045(13)70589-8
Complication rate following implanted-based reconstruction is higher following radiotherapy. This systematic review examines the effect of radiotherapy before or after implant-based reconstruction. Major or minor complication was defined with the former requiring surgical intervention. Reconstruction was deemed a success if patients had the same implant alone at the end of each study period. Out of 1006 citations, 26 citations were taken forward for final analysis. The pooled mild contracture rate was 30% in 98 breasts irradiated prior to reconstruction versus 37% in 672 breasts irradiated post-reconstruction. The pooled severe capsular contracture rated was 25% in 68 breasts irradiated prior to reconstruction versus 32% in 818 breasts irradiated post-reconstruction. The pooled minor complication rate was 18% in 150 breasts irradiated prior to reconstruction versus 31% in 246 breasts irradiated post-reconstruction. The pooled major complication rate was 49% in 252 breasts irradiated prior to reconstruction versus 39% in 708 breasts irradiated post-reconstruction. The pooled rate of reconstruction failure was 19% in 377 breasts irradiated prior to reconstruction versus 20% in 977 breasts irradiated post-reconstruction.
Annals of Surgical Oncology 2014; DOI 10.1245/s10434-013-3284-z
St. Gallen international expert consensus in 2011 stated that ER or PgR expression was positive when the percentage of stained cells exceeded 1%. The tumour hormone receptor status was considered positive when at least one of ER or PgR was positive. Major question included whether the hormone receptor status on core biopsy reflected the equivalent in the surgical specimen, and whether second determination of hormone receptor status on the surgical specimen influenced therapeutic decision making. The study population included 993 patients (1110 tumours) where hormone receptor status was tested on both the core and surgical specimen. Concordance between the core and surgical specimen was 97.75% (1085/1110). When both ER and PgR were >1% in the core biopsies, at least one hormone receptor was >1% in surgical specimen (845 tumours; 76%). Discrepancies were considered when both receptor status was negative on one examination, and at least 1 receptor status was >1% on the other examination. This occurred in 25/1110 cases (2.25%), and in 4/135 cases (3%) following systemic therapy. Amongst 138 cases considered negative (both hormone receptors negative) on core biopsy, 10 cases displayed positive expression on the surgical specimen (7.2%).
The breast journal 2014; DOI 10.1111/tbj.12181
Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. Authors assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease. Between Feb 2, 2003, and Jan 31, 2012, authors recruited postmenopausal women aged 40—70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0—7·1), 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio 0·47, 95% CI 0·32—0·68, p<0·0001). The predicted cumulative incidence of all breast cancers after 7 years was 5·6% in the placebo group and 2·8% in the anastrozole group. 18 deaths were reported in the anastrozole group and 17 in the placebo group, and no specific causes were more common in one group than the other (p=0·836).
The Lancet 2013; doi:10.1016/S0140-6736(13)62292-8
This study evaluates long term upper body physical morbidity following breast reconstruction. Patients who underwent breast reconstruction between 2003-2008 were reviewed. Patients who underwent post-mastectomy radiotherapy and combination of reconstruction procedures were excluded. BREAST-Q was used to assess chest and upper limb morbidity. Questionnaire response rate was 68.1% (308/452). 93/308 underwent mastectomy alone, 74 autologous reconstruction, and 141 two-staged expander reconstruction. Response rate was 51%, 64%, and 69% respectively. Patients who underwent autologous reconstruction had the highest physical well being with a mean score of 82.5/100 (p<0.05), compared to 76.5 for implant-based reconstruction (p<0.05), and 65 for mastectomy alone.
Annals of surgical Oncology 2014; DOI 10.1245/s10434-013-3231-z
Electron intraoperative radiotherapy (ELIOT) involves the delivery of intraoperative radiotherapy. This has potential for avoiding prolonged delivery of external beam radiotherapy and its associated detrimental effect to skin flaps. This equivalence randomised trial compares ELIOT with the conventional external beam radiotherapy with measured outcome of local recurrence and overall survival. Eligibility criteria involved patients aged from 48-75 years old and tumour diameter of up to 2.5cm. One full dose of 21Gy was delivered using ELIOT. External beam radiotherapy involved 50Gy given in 25 fractions, followed by a boost dose of 10Gy given in 5 fractions. All patients who had positive sentinel nodes received axillary nodal dissection. Patients who had 4 of more positive nodes received additional radiotherapy. Patients were followed up in clinic every 3 months, had USS every 6 months, and mammogram yearly. 5 year local recurrence of 3% was assumed in the external radiotherapy group and up to 7.5% in the ELIOT group to assume equivalence. This required a sample size of 412 patients in each group. 1305 patients were randomised, and analysis was performed on 601 patients in the external radiotherapy group and 585 patients in the ELIOT group (2000-2007). The median follow-up was 5.9 years and 5.5 years respectively. 74.6% of patients received endocrine therapy only, 7.7% received chemotherapy only, and 13.8% received both chemotherapy and endocrine therapy. 35 ipsilateral breast tumour recurrence (IBTR) occurred in the ELIOT group, yielding a 5-year event rate of 4.4%. However, IBTR occurred in only 4 cases in the external radiotherapy group, with 5-year event rate of 0.4% (p=0.0001). Hazard ratio was 9.3 for patients allocated ELIOT compared to external radiotherapy. Development of distant metastasis was equivalent in the two groups (5.1% in the ELIOT group versus 4.8% in the external radiotherapy group; p=0.94). 5 year overall survival was 96.8% in the ELIOT group versus 96.9% in the external radiotherapy group. For patients who received ELIOT, 5-year IBTR exceeded 10% in patients with tumour size >2cm, four or more positive lymph nodes, grade 3 tumours, ER negative tumours, and with triple-negative tumours.
Lancet Oncology 2013; DOI;10.1016/S1470-2045(13)70497-2
This study investigates the effect of radiotherapy on implant-based immediate breast reconstruction (2007-2011). The study included patients treated for breast cancer but not patients who received risk reducing surgery. IBR failure was defined as permanent removal of implant with or without secondary breast reconstruction. The secondary outcome was the number of unplanned operations. BREAST-Q was used to evaluate patient satisfaction and health-related quality of life. 725 patients had 754 IBR procedures (mean follow-up of 43 months). 64 patients received prior radiotherapy, and 304 patients received post-operative radiotherapy. 77 patients received neoadjuvant chemotherapy. IBR failure occurred in 83/754 case (11%); 22/386 (6%) without radiotherapy, 16/64 (25%) after prior radiotherapy, and 45/304 (15%) after post-operative radiotherapy (p<0.001). In 39/83 cases, a secondary autologous reconstruction was performed. The estimated 5 year IBR failure rate was 10.4% for non-irradiated, 28.2% for previously irradiated, and 25,2% for post-operatively irradiated patients (log rank p<0.001). Other factors associated with IBR failure was higher age, smoking, post-operative infection, and higher BMI. The use of permanent implant was associated with lower HR for failure. Multivariate analysis showed that irradiation, treating hospital, post-operative infection, higher BMI, and less surgeon reconstructive experience resulted in higher HR for IBR failure. Unplanned operation occurred in 391/751 IBR procedures (52%); 44% in non-irradiated cases, 66% in previously irradiated cases, and 59% in post-operatively irradiated cases (p<0.001). The mean time to unplanned operation was 17 months for the non-irradiated cases, 16 months for the previously irradiated cases, and 17.5 months in post-operatively irradiated cases (p=0.212). For women without IBR failure, 78.7% of women responded to the questionnaire. Radiotherapy significantly worsened PROMs compared to non-irradiated patients, but the scores were not significantly different regarding the two radiotherapy groups.
Breast Cancer Research and Treatment 2013; DOI; 10.1007/s10549-013-2770-0
This study examines oncologist breast cancer follow-up patterns and examines any potential pattern between follow-up patterns and patient and tumour characteristics. SEER-Medicare database was used to identify patients greater than 65 years old diagnosed with breast cancer between 2000 to 2007 (n=39421). The follow-up window began 12 months after diagnosis or a minimum of 3 months after last treatment, excluding endocrine therapy and reconstructive surgery. A minimum of 1 year of follow-up was required. 59% had stage I disease, 36% stage II disease, and 5% stage III disease. Patients had a median of 2.67 follow-up visits per year. Younger age, positive nodes, ER/PR positivity, and increasing intensity of treatment were strongly associated with more frequent follow-up. For example, the odds of having >4 visits per year, compared to <2 visits per year was 1.5 with positive nodes, 1.2 if ER positive, 3.3 if chemotherapy was received. The likelihood of more frequent follow-up increased with intensity of local therapy (using lumpectomy as a reference); mastectomy alone OR of 1.6, lumpectomy with radiation OR of 3.9, and mastectomy with radiation OR of 4.7. Increasing number of oncologists involved in follow-up was associated with increased follow-up frequency. >90% receiving chemotherapy and 60-84% who did not receive chemotherapy were seen by medical oncologists during follow-up. 58% undergoing surgery had surgical oncology follow-up, and 51% treated with radiotherapy had radiation oncology follow-up.
Annals of Surgical Oncology 2013; DOI; 10.1245/s10434-013-3170-8
This study examines outcome in patients diagnosed with isolated sternal and full-thickness chest wall (SCW) recurrences who were treated surgically and non-surgically. 44 patients underwent radical resection versus 32 patients who were managed without surgery (1992-2011; median follow-up of 3.6 years). Median age at diagnosis was 44.5 years old. 45% were treated initially with mastectomy and radiotherapy, 29% with mastectomy alone, 22% with breast conserving surgery and radiotherapy, and 4% with breast conserving surgery alone. 54% of the cohort had ER positive tumours. 23% were HER2 positive. 40% had triple-negative tumours. The median time to recurrence was 2.7 years. 52% of the patients who underwent radical resection had further recurrence diagnosed within 2 years, compared to 25% in the non-surgical group (p=0.017). Patients who underwent surgery were more likely to present with triple-negative tumours (52% versus 17%; p=0.006). Patients undergoing surgery was more likely to have responsive or stable disease after treatment with systemic therapy (54% versus 25%; p=0.04). Radiotherapy was received by 91% in the non-surgical cohort versus 68% in the surgical cohort; p=0.02). 11/44 underwent sternal resection, 11/44 underwent resection of ribs/chest wall alone, 11/44 underwent resection of sternum and rib/chest wall, and 11/44 underwent resection of sternum and rib/chest wall along with other structures and organs. Soft tissue reconstruction was performed using pectoralis major muscle (n=18), free rectus abdominis muscle (n=9), and combination of soft tissue reconstruction in 15 patients. 5 year OS rate was 39.5% with PFS rate of 22.7%. OS rate was similar in patients who underwent surgery versus those treated conservatively (30.6% versus 49.6%; p=0.52).Similar findings were noted regarding PFS with PFS of 30.2% for patients who underwent surgery versus PFS of 14.8% for patients treated conservatively (p=0.19). On multivariate analysis, ER negative recurrences were associated with poorer PFS (HR 1.75; p=0.04). Amongst patients with ER positive recurrences, 5 year PFS was 46.3% in the surgical group versus 14.5% in the non-surgical group (p=0.01).
Annals of Surgical Oncology 2013; DOI; 10.1245/s10434-013-3202-4
This study examines the potential impact of the Z0011 trial in older (age>65 years old) patients diagnosed with node positive breast cancer after undergoing SLNB using a SEER-medicare database (2001-2007; n=6942). The trial inclusion criteria were applied to determine which patients would have met the eligibility criteria. 2637 (38%) patients met the Z0011 trial criteria, and 1214 patients (46%) received completion ALND, whereas 1423 patients (54%) did not receive completion ALND. Patients who received completion ALND were likely to be younger (p<0.01), had fewer co-morbidities (p=0.05), and more likely to receive chemotherapy (p<0.001). In the same period, 2688 patients underwent mastectomy and SLNB, and 1881 patients (70%) were diagnosed with one or two positive SLNs. 877/1881 (53%) and underwent completion ALND, reflecting the findings observed in patients treated with breast conserving surgery.
Annals of Surgical Oncology 2013; DOI; 10.1245/s10434-013-3193-1
This study evaluates the integrated multidisciplinary care for patients diagnosed with BRCA-gene mutation. The team consisted of plastic surgeon, gynaecological surgeon, geneticist, and nurses. For patients who carry BRCA mutations, they are recommended annual screening mammogram starting between the age of 25 to 35 years old. Patients are informed of potential risk reducing surgery in terms of laparoscopic bilateral salpingo-oophorectomy with or without hysterectomy as well as skin and nipple sparing mastectomy with immediate breast reconstruction. On the day of the procedure, gynaecological procedure is performed first, followed by the breast surgery. 22 patients underwent such simultaneous risk reducing surgery between 2005 to 2011. The mean patient age was 41.2 years old. 6/22 were BRCA1 carriers, 10/22 were BRCA2 carriers, and the remainder were carriers of both. In majority, fixed volume implants were used. The average total operating time was 3 hours and the average stay in hospital was 2.5 days. 2 patients developed complications including haematoma, accidental bladder perforation, and breast wound infection. One stage procedure was more cost effective with estimated average cost of £5000 per patient, compared to £6400 per patient for the two stage procedure.
European Journal of Surgical Oncology 2013; DOI; 10.1016/j.ejso.2013.09.018
This study evaluates concordance between the use of indocyanine green (ICG) and the current standardised method of technetium 99m (99mTc) for sentinel node localisation in the axilla. The study involved 134 patients between 2011 to 2013. Patients had 99mTc injected on the afternoon the day before surgery, and had ICG injected on table immediately before surgery. ICG fluorescence was detected by photodynamic eye camera. ICG positive lymph nodes were excised and examined for residual fluorescence as well as radioactivity using a gamma probe. Further sentinel nodes were excised where significant residual radioactivity was detected in the axilla. 97% sentinel node detection rate was assumed for the 99mTc technique with a dis concordance rate of 6%. Therefore, 255 sentinel nodes required examination to demonstrate equivalence between the two methods with 80% power and type 1 error of 5%. 246 sentinel nodes were detected by one or both methods in 134 patients. 1, 2, or 3 sentinel nodes were detected in 70 (52.2%), 39 (29.1%), and 17 (12.7%) respectively. 4 or more sentinel nodes were excised in 8 patients. 99mTc detected sentinel nodes in 231/246 cases (93.9%), and ICG detected sentinel nodes in 245/246 cases (99.6%). This resulted in a concordance rate of 93.5% with 95% confidence interval of 2.6 to 8.8%.
European Journal of Surgical Oncology 2013; DOI; 10.1016/j.ejso.2013.10.004
This study aims to analyse clinical and biological features and patterns of recurrence in very young patients with breast cancer. The age groups were classified by <25 years old, 25-29 years old, and 30-34 years old. The cohort included patients diagnosed with breast cancer at European institute of oncology between 1995 to 2006. Patients who had previous cancer in another site, treated with neoadjuvant therapies, metastatic presentation, and bilateral cancers were excluded from the study. The cohort included 497 patients; <25 years old (n=22), 25-29 years old (n=123), and 30-34 years old (n=352). Patients aged <25 years old had higher percentage of T1 tumours compared to other two groups. However, the youngest group also had highest percentage of tumours >4cm. No significant difference was found between the 3 groups regarding nodal status. Patients <25 years old had poorly differentiated tumour in 81.8%, compared to 66.7% in those 25-29 years old, and 56.5% in those aged 30-34 years old. The youngest group also had the highest percentage of luminal B tumours, and no patients with HER2 subtype was detected in the same group. However, no statistical significance was detected between the three groups regarding the Perou subtypes. Similarly the distribution of chemotherapy regimen and endocrine therapy distribution was similar between the three groups. With median follow up of 5.7 years, no differences were found regarding disease free survival, overall survival, loco regional and distant metastasis rates, as well as contralateral breast cancer rates between the three groups.
The Breast 2013; DOI; 10.1016/j.breast.2013.08.006
Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor (HER2) concordance between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and Oncotype DX, a commercially available RT-PCR-based assay which recently began reporting biomarker results was assessed. ER concordance was 98.9% (262/265), Pearson correlation coefficient (r) = 0.42, and Spearman's rank correlation (ρ) = 0.25. Positive percent agreement for ER was 98.9% (262/265). One patient with discordant ER results was not offered hormone therapy based on the preferential use of Oncotype DX. PR was concordant in 91.3% (242/265), r = 0.80, ρ = 0.75, and Cohen's kappa (κ) = 0.63. Positive percent agreement for PR was 90.5% (218/241) and negative percent agreement was 100% (24/24). HER2 concordance was 99.2% (245/247), r = 0.35, ρ = 0.28, and κ = 0.12. Positive percent agreement for HER2 was 0% (0/2) and negative percent agreement was 100% (245/245). Of the three FISH HER2-amplified cases, two were negative and one was equivocal, and all FISH HER2-equivocal cases (n = 3) were negative by Oncotype DX. Patients that were FISH HER2-amplified, Oncotype DX HER2-negative did not receive trastuzumab. Although our results demonstrated high concordance between IHC and Oncotype DX for ER and PR, our data showed poor positive percent agreement for HER2. Compared to FISH, Oncotype DX does not identify HER2-positive breast carcinomas.
The Breast Journal 2013: DOI: 10.1111/tbj.12223
The impact of close margins in patients with ductal carcinoma-in situ (DCIS) treated with mastectomy is unclear; however, this finding may lead to a recommendation for postmastectomy radiotherapy (PMRT). Authors sought to determine the incidence and consequences of close margins in patients with DCIS treated with mastectomy. The records of 810 patients with DCIS treated with mastectomy from 1996 through 2009 were reviewed. Clinical and pathologic factors were analyzed with respect to final margin status. Median follow-up was 6.3 years. Overall, 94 patients (11.7 %) had close margins (positive, n = 5; negative but ≤1 mm, n = 54; 1.1–2.9 mm, n = 35). Independent risk factors for close margins included multicentricity, pathologic lesion size ≥1.5 cm, and necrosis, but not age, use of skin-sparing mastectomy, or immediate reconstruction (p > 0.05). Seven patients received PMRT, and none had a locoregional recurrence (LRR). Among the remaining 803 patients, the 10-year LRR rate was 1 % (5.0 % for margins ≤1 mm, 3.6 % for margins 1.1–2.9 mm, and 0.7 % for margins ≥3 mm [p < 0.001]). The 10-year rate of contralateral breast cancer was 6.4 %. On multivariate analysis, close margins was the only independent predictor of LRR (p = 0.005).
Annals of Surgical Oncology 2013: DOI: 10.1245/s10434-008-9952-8
Malignant phyllodes tumors of the breast have traditionally been treated with surgical excision. Recently, the use of adjuvant radiotherapy has been advocated to reduce the risk of local recurrence; however, this recommendation is controversial in the absence of consistent outcome data. Authors hypothesize that there has been a trend toward increased utilization of adjuvant radiotherapy for malignant phyllodes tumors despite its uncertain effect on outcomes. Using the National Cancer Data Base, predictors of radiotherapy utilization were examined for women with malignant phyllodes from 1998 to 2009. Of the 3,120 patients with malignant phyllodes, 57 % underwent breast conservation surgery and 42 % underwent mastectomy. Overall, 14.3 % of women received adjuvant radiotherapy. Utilization of radiotherapy doubled over the study period (9.5 % in 1998–1999 vs. 19.5 % in 2008–2009, p < 0.001). Women were significantly more likely to receive radiotherapy if they were diagnosed later in the study, were age 50–59 years old, had tumors >10 cm, or had lymph nodes removed. For the 1,774 patients with available recurrence data, overall recurrence was 14.1 %, and LR was 5.9 %. In adjusted models, adjuvant radiotherapy reduced LR (aHR 0.43, 95 % CI 0.19–0.95) but did not impact DFS or OS after 53 months’ median follow-up.
Annals of Surgical Oncology 2013: DOI: 10.1245/s10434-008-9952-8
This study examines if larger amount of tissue obtained by core needle biopsy (CNB) for papillary lesion could distinguish a group of patients who could be safely followed up, and spared surgical excision. 183 patients were identified who were diagnosed with papillary lesion on CNB (2000 to 2010), and 113 patients were excluded as they had atypia or malignancy on core biopsy. Further 19 patients were excluded due to lack of excision biopsy at the author’s institution. This resulted in a cohort of 51 patients who had diagnosis of benign papilloma on CNB who underwent subsequent excision biopsy. At least three levels were examined on each CNB sample. 6/51 (11.7%) excisions revealed significant lesions not present on CNB (3 had ADH, and 3 had invasive or in situ carcinomas). The mean patient age at core biopsy was 50.2 years old. CNB was performed after abnormal screening mammogram in 62%. Patients presented with nipple discharge in 9.8%, and presented with palpable mass in 28%. 37 lesions were classified as BIRADS 4 and 3 lesions as BIRADS 3. 71% of the lesions measured <1cm. Papilloma found to be benign on excision had mean radiological size of 9.1mm, compared to 10.8mm with lesions containing atypia or malignancy on excision (p=0.51). CNB size ranged from 9 to 18 gauges (median 14). Of 9 patients who had CNB with 12-,11-, or 9-gauge needles, none had atypia or malignancy upon excision. The number of CNB sample ranged from 3 to 16 (median 4). Logistic regression showed that CNB samples greater than or equal to 7 cores, independent of needle gauges, had negative predictive value for ADH/malignancy of 100% (AUC of 0.69). the aggregate area of tissue ranged from 20 to 450 mm2. Patients whose excision revealed ADH or malignancy had significantly less CNB tissue sampled (41.7mm2vs 101.5mm2; p=0.003). Logistic regression showed that CNB tissue sample measuring >96mm2 in aggregate had a negative predictive value for ADH/malignancy of 100% (AUC of 0.68).
Annals of Surgical Oncology 2013; DOI; 10.1245/s10434-013-3191-3
This study evaluates the incidence of close or positive margins in patients with DCIS treated with mastectomy (1996-2009; n=810 with median follow-up of 6.32 years). Margin status was categorised to positive, <1, 1.1-2.9, and >3mm. 7 patients received post-mastectomy radiotherapy (PMRT). Intra-operative analysis showed margin of <3mm in 14.3% (n=116); re-excision resulted in change to margin >3mm in 103/116 patients (89%). 9 patients required second procedure to clear margins <3mm. Final histopathology results showed that 5 patients (0.6%) had positive margins, 54 patients (6.7%) had <1mm margins, 35 patients (4.3%) had margins between 1.1 and 2.9mm, and 716 patients (88.4%) had margins >3mm. Univariate analysis showed that patients were more likely to have close margins if they were <50 years old, underwent skin sparing mastectomy or immediate breast reconstruction, had multicentric, multifocal, or comedo-type DCIS, had evidence of necrosis, or had large tumour size. Multivariate analysis showed that the only independent predictors of margin <3mm were multicentricity, presence of necrosis, and largest recorded pathological tumour size >1.5cm. 8 patients developed locoregional recurrence (LRR) with median time to LRR of 2.8 years. This resulted in 10 year LRR of 1% amongst patients who did not receive PMRT. Univariate analysis showed that margin status, multicentricity, and multifocality predicted LRR. Multivariate analysis showed that the only independent predictor of LRR was margin <3mm (HR of 8.4, CI 1.9 to 37; p=0.005). 546 patients did not have contralateral prophylactic mastectomy, have bilateral breast cancer, or have past history of contralateral breast cancer. 30/546 patients developed contralateral breast cancer during follow-up, representing a 10-year contralateral breast cancer incidence of 6.4%.
Annals of Surgical Oncology 2013; DOI; 10.1245/s10434-013-3194-0
Intraoperative radiotherapy with electrons allows the substitution of conventional postoperative whole breast irradiation with one session of radiotherapy with the same equivalent dose during surgery. However, its ability to control for recurrence of local disease required confirmation in a randomised controlled trial. This study was done at the European Institute of Oncology (Milan, Italy). Women aged 48—75 years with early breast cancer, a maximum tumour diameter of up to 2·5 cm, and suitable for breast-conserving surgery were randomly assigned in a 1:1 ratio (using a random permuted block design, stratified for clinical tumour size [<1·0 cm vs 1·0—1·4 cm vs ≥1·5 cm]) to receive either whole-breast external radiotherapy or intraoperative radiotherapy with electrons. Patients in the intraoperative radiotherapy group received one dose of 21 Gy to the tumour bed during surgery. Those in the external radiotherapy group received 50 Gy in 25 fractions of 2 Gy, followed by a boost of 10 Gy in five fractions. This was an equivalence trial; the prespecified equivalence margin was local recurrence of 7·5% in the intraoperative radiotherapy group. The primary endpoint was occurrence of ipsilateral breast tumour recurrences (IBTR); overall survival was a secondary outcome. 1305 patients were randomised (654 to external radiotherapy and 651 to intraoperative radiotherapy). After a medium follow-up of 5·8 years (IQR 4·1—7·7), 35 patients in the intraoperative radiotherapy group and four patients in the external radiotherapy group had had an IBTR (p<0·0001). The 5-year event rate for IBRT was 4·4% (95% CI 2·7—6·1) in the intraoperative radiotherapy group and 0·4% (0·0—1·0) in the external radiotherapy group (hazard ratio 9·3 [95% CI 3·3—26·3]). During the same period, 34 women allocated to intraoperative radiotherapy and 31 to external radiotherapy died (p=0·59). 5-year overall survival was 96·8% (95% CI 95·3—98·3) in the intraoperative radiotherapy group and 96·9% (95·5—98·3) in the external radiotherapy group. In patients with data available (n=464 for intraoperative radiotherapy; n=412 for external radiotherapy) we noted significantly fewer skin side-effects in women in the intraoperative radiotherapy group than in those in the external radiotherapy group (p=0·0002).
The Lancet Oncology; 2013: doi:10.1016/S1470-2045(13)70497-2
This systematic review investigates outcome in patients treated with nipple sparing mastectomy (NSM). 48 studies met the inclusion criteria. 65% of studies were retrospective and 35% prospective. There were no level I or I studies. There were total of 5166 patients with 6615 NSM. The average was 45.7 years with average BMI of 23.98. Pooled analysis showed overall complication rate of 22% and Nipple necrosis rate of 7%. Loco-regional recurrence rate was 1.8%, with distant metastasis rate of 2.2%. Of 5218 reconstructions, 45.5% were two stage expander to implant, 40.7% were one stage direct to implant! and 13.8% were autologous reconstructions. Overall complication rate of 52.8% and nipple necrosis of 4.5% was reported for the two stage procedure. The respective figures were 16.7% and 4.1% for direct to implant procedure, and 23.7% and 17.3% for the autologous procedure. The most common incision type was radial, followed by periareolar, inframammary, mastopexy, and transareolar. The nipple necrosis rate was 8.83%, 17.81%, 9.09%, 4.76%, and 81.82% respectively.
Plastic and Reconstructive surgery 2013; DOI; 10.1097/PRS.0b013e3182a48b8a
This multi-institution study investigates outcome in patients who undergo expander or implant reconstruction with (n=3301) or without (n=15799) acellular dermal matrix (ADM). American College of Surgeons National Surgical Quality Improvement Program Data (2005-2011) set was used retrospectively. 30 day post-operative data was collected using a survey via letter or telephone call. The average age of the ADM group was 50.7 years old versus 51.3 years old in the non-ADM group. Immediate implant reconstruction was performed in 10.8% of the ADM group versus 19.5% in the non-ADM group. Tissue expanders were used initially in 86.8% of the ADM group versus 72.5% in the non-ADM group. 13.7% of the ADM group were smokers and 4.5% were diabetic. Radiotherapy had been administered previously by 0.3% of the ADM group. In the non-ADM group, 13.4% were smokers, 4.9% were diabetic, and 0.4% had prior radiotherapy. Complication rates were similar between the two groups (p=0.396) with overall complication rate of 5.3% in the ADM group and 4.9% in the non-ADM group. 7.2% of ADM group required return to theatre versus 6.5% in the non-ADM group (p=0.136). In the non-ADM group, smoking (p<0.001) and BMI (0.01) was associated with graft/prosthesis/flap failure. BMI predicted superficial surgical site infection (p=0.001). In the ADM group, the likelihood of wound disruption was increased by BMI (p=0.01) and diabetes (p=0.02). Sepsis was associated with BMI (p=0.01) and alcohol consumption (p=0.04).
Plastic and Reconstructive surgery 2013; DOI; 10.1097/PRS.0b013e3182a3beec
The aim of this study was to identify risk factors for invasive breast cancer in patients diagnosed with ductal carcinoma in situ (DCIS) on a preoperative biopsy. These factors were used to develop a nomogram for predicting the risk of invasion in the preoperative setting. This was a retrospective analysis of patients who underwent surgical treatment for DCIS diagnosed before surgery between 1997 and 2009. Multivariable analysis was used to identify clinical, radiological and histopathological factors that may predict upstaging. A nomogram was developed to predict the probability of invasion using multiple logistic regression analysis. This nomogram was subsequently validated using another cohort of patients with a preoperative diagnosis of DCIS between 2010 and 2012. Upstaging to invasive cancer occurred in 123 (24.9 per cent) of 493 women treated between 1997 and 2009. A larger DCIS lesion (at least 15 mm), lack of hormone receptor expression, intermediate or high nuclear grade, diagnosis on core biopsy compared with vacuum‐assisted biopsy, and non‐cribriform subtype of DCIS were significantly associated with upstaging. A nomogram developed using these factors demonstrated good predictive performance (area under the receiver operating characteristic (ROC) curve (AUC) 0·823, 95 per cent confidence interval 0·787 to 0·860). The nomogram showed similar predictive performance in the validation data set, based on another 149 women (AUC 0·700, 0·613 to 0·786).
British Journal of Surgery 2013; DOI: 10.1002/bjs.9337
This study examines the outcome of patients who go onto have Oncoplastic breast surgery (OBS) after neoadjuvant chemotherapy (NACT), compared to standard BCS techniques. Of 259 patients who underwent BCS, 45 underwent OBS (18%). The two groups were different in terms of ER status and tumour location only. OBS techniques involved round block technique (n=13), re-centering of the NAC (n=3), ablation of NAC (n=5), external radial mammoplasty (n=2), inferior pedicle mammoplasty (n=8), vertical mammoplasty (n=1), superior pedicle mammoplasty (n=11), and cutaneous resection with a rotational flap (n=2). The volume excised breast tissue was greater in the OBS group than standard BCS (180cm3 versus 98cm3, p<0.001). The median tumour size was similar in both groups (p=0.66), but pCR rate was lower in the OBS group (p=0.01). The re-excision or mastectomy rates were similar (p=0.22 and p=0.3), and the number of re-operations for post-operative complication was higher in the OBS group (2% versus 1%; P=0.007). Multivariate analysis showed that the risk factors for completion mastectomy was the presence of microcalcifications on mammogram (p=0.009), number of positive axillary lymph nodes (p=0.005), and the type of tumour regression (p=0.04). The type of surgery did not impact on the time to adjuvant treatment (p=0.38). The result of the cosmesis survey did not reveal any difference between the two groups (p=0.52). 5 year RFS was 92.7% in the OBS groups versus 92.1% in the BCS group.
The Breast 2013; DOI; 10.1016/j.breast.2013.07.055
This study determines the risk factors for residual disease on the re-excision specimens for involved or closed margins for invasive ductal carcinomas (IDC), and whether re-excision impacted on local ipsilateral relapse (LIR) rate. The study involved 454 patients from 1992 to 2002. All patients were treated with radiotherapy and exclusion criteria were T4 tumours, and patients treated with neoadjuvant therapy. Clear margin was defined as >3mm, and patients with margins equal to or less than 3mm either underwent re-excision (n=206) or observed (n=248) without randomisation. LIR rate was determined at 5 years. In cases of involved margins, pathological analysis involved histological types (infiltrative or intraductal) and spread (focal or extensive). Regarding patients who underwent re-excision, 55 patients (26.7%) had residual disease on the re-excision specimen. This figure was higher at 47.7% when re-excision was performed for diffuse margin involvement. Univariate analysis showed that factors predictive of residual disease were the proportion of IDC in the primary tumour, the number of involved margins, and the histological subtype at the margins. Multivariate analysis showed only a margin involved with IDC remained predictive of residual disease. The odd ratio for a margin involved with diffuse IDC versus close was 4.2 (p=0.011). With median follow-up of 6.2 years, the 5 year LIR rate was 5.3% for the re-excision group versus 11.8% for the observed group. In the latter group, the risk factors for LIR were hormone therapy, diffuse involved margin, and intraductal subtype involving the margin on multivariate analysis. In the latter group, patients with margin involved with diffuse IDC had 5-year local relapse free survival of 49% versus 92% for a margin involved with focal disease. When the two groups were compared, independent prognostic factors for local relapse free survival were hormone therapy and re-excision of a margin involved with diffuse disease, either with infiltrative carcinoma (p=0.038) or IDC (p<0.001). Re-excision for close margins or margins involved with focal disease did not improve LIR rate.
Annals of Surgical Oncology 2013; DOI; 10.1245/s10434-013-3063-x
This study describes a novel level 2 oncoplastic technique (LIQ-V) for resecting breast cancers in the lower inner quadrant. This technique involves wide excision of a large portion of LIQ including the skin. Breast is re-shaped by medial advancement of the remaining lower quadrant after incising the submammary fold and completely undermining the lower pole. 22 patients underwent a LIQ-V technique between 2004 to 2011. Mean patient age was 58 years. Breast cup size was B cup in 41%, C cup in 45%, D cup in 9%, and E cup in 5%. Patients treated had invasive cancer in 14 cases and DCIS in 8 cases. The mean radiological tumour size was 24mm (range 9-60mm) for invasive cancers (n=14), and 35mm for DCIS (n=8; range 5-60mm). The mean resection weight was 101g (range 17-201g) for invasive cancers, and 117g (range 50-170g) for DCIS. Margins were clear in 21 cases. The pathological tumour size was 19mm for invasive cancers, and 27mm for DCIS. 3 patients underwent contralateral reduction mammoplasty to avoid breast asymmetry. Regarding post-operative complications, 2 patients developed fat necrosis (9.1%) treated conservatively. With mean follow-up of 55 months, 1 patient developed cancer recurrence. Cosmetic evaluation performed by independent surgeons were reported as excellent (68%), good (26%), and fair (5%).
Annals of surgical Oncology 2013; DOI; 10.1245/s10434-013-3085-4
This study reports the pattern of palliative surgery in breast cancer patients with distant metastatic disease (DMD). The data from Basel breast cancer database was available from 1990 (n=1459). 363 patients had confirmed DMD with median time between primary cancer diagnosis and diagnosis of DMD of 38.5 months. Patients who were alive at present had minimum follow-up of 2 years: 316/363 (87.1%) died of metastatic disease, 24/363 (6.6%) died of other causes, 20/363 (5.5%) were alive with metastatic disease, and 3/363 (0.8%) were alive with no evidence of metastatic disease. The 340 patients who died were examined to determine the surgical procedures during the palliative period. All surgery was performed to alleviate metastasis-related symptoms. 127 surgical procedures were performed in 100 patients (29.4%). The most common site was breast (n=60), followed by bone to stabilise osseous structures due to metastasis (n=50). The remainder included lung (n=1), liver (n=1), and brain (n=4). In addition 11 procedures were performed at other locations including ovary, skin, bladder, gallbladder, and mediastinal lymph nodes. There was no significant difference in age of patients between those who underwent surgery compared to those that did not (63.5 years versus 65 years; p=0.391). Local recurrences (19.7%) and bony metastasis (15.6%) were the most frequently surgically treated locations. 40.4% of operations were carried out in the first third of metastatic disease survival, 29.8% were carried out in the middle third, and 29.8% in the final third. The median survival after surgery was 18 months. 94% of the patients who had surgery were also initiated on systemic therapy, compared to 83.7% in those who did not undergo surgery (p=0.013).
European Journal of Surgical Oncology2013; DOI;10.1016/j.ejso.2013.08.015
This study reports the uptake of breast reconstruction after prophylactic mastectomy in BRCA mutation carriers from eight countries. 1635 patients had prophylactic mastectomies. 990 patients (60.6%; mean age 44.5 year old) had previous diagnosis of unilateral breast cancer, and 645 patients (39.4%; mean age 42.5 years old; p<0.0001) had bilateral prophylactic mastectomies. For those with unilateral breast cancer, the mean time from breast cancer diagnosis to contralateral prophylactic surgery was 3.2 years. The rate of reconstruction varied from 50% in China, compared to 85.7% in France. Overall, 1137/1635 (69.1%) had breast reconstruction. 824/1137 (72.5%) had implant-based reconstruction, 241/1137 (21.2%) had autologous reconstruction, and 62/1137 (5.5%) had combined procedure using autologous and implant reconstruction. The mean age at the time of prophylactic mastectomy for those who underwent reconstruction was 42.3 years, compared to 47.1 years for those who did not undergo reconstruction (p<0.0001). Women with age >45 years old were 64% less likely to have reconstruction, compared to patients younger than 35 years old (OR 0.36, 95% CI 0.26-0.5; p<0.001). For those who had previous diagnosis of breast cancer, 62.9% had breast reconstruction after prophylactic mastectomy, compared to 79.7% in patients with no previous diagnosis of breast cancer (OR 0.48, 95% CI 0.38-0.61, p<0.001). Of the 314 patients who had breast conserving surgery as the original cancer surgery, 75.2% had subsequent contralateral breast reconstruction. However, of the 676 patients who had mastectomy as the original cancer surgery, 57.1% had contralateral reconstruction (OR 2.79, 95% CI 2.02-3.85; p<0.001).
Annals of Surgical Oncology 2013; DOI; 10.1245/s10434-013-3040-4
Breast augmentation is one of the most commonly performed operations. Three-dimensional outcome simulation can be used to predict and demonstrate for the patient what the planned operation aims to achieve in terms of size and shape. A prospective series of 150 patients underwent breast augmentation following consultation with the aid of three-dimensional simulation images. These patients were evaluated with a questionnaire 6 months postoperatively. A retrospective chart review of 52 patients whose three-dimensional simulations were compared with the postoperative photographs were evaluated and graded by an independent panel of investigators. The independent panel graded the overall similarity of the three-dimensional simulations to the actual breasts with a total average score ± SD of 7.5 ± 0.80 (range, 4.5 to 8.9) using a visual analogue scale ranging from 1 to 10. The highest average score was given to projection, breast width, and height (7.8); the lowest average score was given to intermammary distance (7.0). Eighty-six percent of patients felt the simulated image was very accurate in predicting the actual result of their breasts.
Plastic & Reconstructive Surgery 2013; doi: 10.1097/PRS.0b013e3182a014cb
This trial examines false negative rate (FNR) of SNB after neoadjuvant chemotherapy (NAC) in women presenting with cN1 disease. The pre-NAC axillary metastasis was diagnosed using fine needle aspiration or core biopsy. At the end of NAC regimen, patients underwent axilla USS, and underwent SNB and then ALND. At least 2 SNs were excised. The study was designed to determine the likelihood of FNR of SNB of greater than 10%. The cohort involved 701 patients (663 patients with cN1 disease and 38 with cN2 disease), and 687 patients underwent SNB and ALND. 525 patients with cN1 disease had at least 2 SNs excised, and underwent cALND. 215 patients had no residual disease (cPR rate of 41%). In 108 patients, the residual disease was confined to the SLNs (20.6%). In 39 patients, the disease was confined to the nodes removed at ALND only (7.4%). The disease was confined to nodes from both SNB and ALND in 163 patients (31.1%). This resulted in a FNR of 12.6%.
The Journal of the American Medical Association 2013; DOI;10.1001/jama.2013.278932
Increased mammographic density is associated with increased risk of unilateral breast cancer. However, how mammographic density affects the risk of contralateral breast cancer (CBC) is investigated by this study. This included 211 cases versus 211 healthy controls. The mean time to follow-up mammogram after diagnosis was 1.6 years. The mean density at baseline was 28%. No association was seen between baseline mammogram density and the risk of CBC. There was a 55% lower risk of CBC for women with an absolute decrease in mammographic density of >10% from baseline to the follow-up mammogram. Similarly, 46% decrease in the risk of CBC was seen for women with decrease in mammographic density of >10 cm2.
Breast Cancer Research 2013; DOI; 10.1186/bcr3451
Authors studied the effect on tumour response to neoadjuvant therapy of the substitution of lapatinib for trastuzumab in combination with weekly paclitaxel after doxorubicin plus cyclophosphamide treatment, and of the addition of lapatinib and trastuzumab combined after doxorubicin plus cyclophosphamide treatment in patients with HER2-positive operable breast cancer to determine whether there would be a benefit of dual HER2 blockade in these patients.
This was an open-label, randomised phase 3 trial. Each received four cycles of standard doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 intravenously on day 1 every 3 weeks followed by four cycles of weekly paclitaxel (80 mg/m2) intravenously on days 1, 8, and 15, every 4 weeks. Concurrently with weekly paclitaxel, patients received either trastuzumab (4 mg/kg load, then 2 mg/kg intravenously) weekly until surgery, lapatinib (1250 mg orally) daily until surgery, or weekly trastuzumab plus lapatinib (750 mg orally) daily until surgery. After surgery, all patients received trastuzumab to complete 52 weeks of HER2-targeted therapy. Randomisation (ratio 1:1:1) was done centrally with stratification by clinical tumour size, clinical nodal status, hormone-receptor status, and age. The primary endpoint was the pathological complete response in the breast. 519 patients had their pathological response determined. Breast pathological complete response was noted in 93 (52·5%) of 177 patients in the trastuzumab group, 91 (53·2%) of 171 patients in the lapatinib group (p=0·9852); and 106 (62·0%) of 171 patients in the combination group (p=0·095). The most common grade 3 and 4 toxic effects were neutropenia (29 [16%] patients in the trastuzumab group [grade 4 in five patients (3%), 28 [16%] in the lapatinib group [grade 4 in eight patients (5%)], and 29 [17%] in the combination group [grade 4 in nine patients (5%)]) and grade 3 diarrhoea (four [2%] patients in the trastuzumab group, 35 [20%] in the lapatinib group, and 46 [27%] in the combination group; p<0·0001). Symptomatic congestive heart failure defined as New York Heart Association Class III or IV events occurred in seven (4%) patients in the trastuzumab group, seven (4%) in the lapatinib group, and one (<1%) in the combination group; p=0·185).
The Lancet Oncology;2013: doi:10.1016/S1470-2045(13)70411-X
This study investigates relationship between surgical margin distance and loco-regional recurrence (LRR) in patients with invasive breast cancer (IBC) using a cohort of patients from BCTQAP (1997 to 2007). All patients had minimal 3 years of clinical follow-up. The nearest invasive margin was categorised between 0 and 5 mm, and >5 mm. The study cohort included 1123 patients who had BCS (968 had one operation, 149 had two operations, and 6 had three operations). In addition, out of 1177 patients who underwent mastectomy, 297 were due to involved margins after BCS. Therefore, 452 patients had re-excision or mastectomy following original BCS. LRR occurred in 88 patients. The mean follow-up was 7.9 years, with mean time to LRR of 4.2 years. On univariate analysis, the following factors were associated with higher risk of LRR; age <50 years old, pre-menopausal status, breast cancer detected on self-examination, tumour size>20mm, grade 2 or 3 IBC, positive nodal status, presence of LVI, and ER negativity. ‘Close’ margin of >0 to <2mm was associated with increased risk of LRR (HR= 3.27; 95% CI 1.83 to 5.84; p=0.001). On multivariate analysis, involved margin or margin of 1mm were associated with increased risk of LRR (HR 3.24, p=0.004; HR 2.72, p=0.008, respectively).Margin distance of 2mm or greater showed no increased risk of LRR.
The Breast 2013; DOI; 10.1016/j.breast.2013.02.018
This study investigates the outcome in patients who had negative versus positive (plus ALND) sentinel node biopsy (SNB) in early breast cancer patients (2000 to 2012; median follow-up of 47 months). The cohort included 889 patients. The study involved invasive breast cancer size of <30mm on imaging or <35mm on histology. 87/889 patients were diagnosed with DCIS. The incidence of positive nodes was 24%. Axillary recurrence occurred in 0.8% of the cohort. The incidence of axillary recurrence was 1.2% in positive SNB patients, and 0.8% in negative SNB patients. The overall loco-regional failure rate was 3.2%. The incidence of distant recurrence was 3.3% for SNB negative patients versus 4.6% for the SNB positive patients. The overall mortality was 4.4% in the entire cohort, with specific mortality of 1.7%. Specific mortality for SNB positive patients was 2.5%, compared to 1.4% in patients who were SNB negative.
The Breast 2013; DOI; 10.1016/j.breast.2013.04.015
The authors assess the risk and safety profiles of both implant and autologous breast reconstructions in the morbidly obese population using the National Surgical Quality Improvement Program data sets. The authors reviewed the 2005 to 2010 National Surgical Quality Improvement Program databases, identifying encounters for Current Procedural Terminology codes including either implant-based reconstruction or autologous reconstruction. Patients were classified and compared based on World Health Organization obesity criteria. Complications were divided into three categories: major surgical complications, wound complications, and medical complications. During the study period, 15,937 breast reconstructions were identified. The incidence of obesity was 27.1 percent, with 4.0 percent defined as class III (morbidly) obese. Morbidly obese patients had significantly higher rates of almost all complications compared with nonobese patients, including major surgical complications (p < 0.001), medical complications (p < 0.001), respiratory complications (p = 0.015), venous thromboembolism (p = 0.001), and wound complications (p < 0.001). These patients also were more likely to require a return to the operating room both for any reason (p < 0.001) and specifically for prosthesis/flap failure (p < 0.001). Morbid obesity was found to be an independent predictor of wound complications (OR, 2.1; p < 0.001), surgical complications (OR, 1.6; p < 0.001), medical complications (OR, 1.6; p = 0.01), and return to the operating room (OR, 1.5; p < 0.001). There was no significant difference in the 30-day surgical complication rates between implant and autologous reconstructions in the morbidly obese (p = 0.23).
Plastic & Reconstructive Surgery;2013: doi: 10.1097/PRS.0b013e31829fe33c
High level of discordance between lymphoscintigraphy techniques could affect outcomes in breast cancer
Several different lymphoscintigraphy (LSG) injections are in use for locating the sentinel node (SN). This study compares exact anatomical location of SLNs with different LSG injection techniques in the same patient using SPECT/CT technology. This multi-centre trial (2009-2011) included patients who underwent double sequential LSG, which were separated by 2-7 days. All patients had clinically negative axilla. LSG were divided into subareolar and peritumoural injections. Early high resolution planar digital image were acquired for 5 minutes after the injection. Delayed images were performed at one to three hours, and SPECT/CT was also performed at this time. 39 patients were recruited for the study. The rate of successful axillary SN mapping was 87% in the subareolar and 95% with the peritumoural injections. 2 patients failed axillary lymphatic mapping. The overall rate of discordance was 56% between the two injection techniques. Patients with medial and central tumours, compared to lateral tumours, were 5 times more likely to be discordant (p=0.2; Odds ratio=5.2; 95% CI: 1.3 to 20).
European Journal of Surgical Oncology 2013; DOI; 10.1016/j.ejso.2013.06.006
Ki-67 and ER expression post-neoadjuvant chemotherapy could predict patient outcome in breast cancer
This study evaluates the role of ER and Ki-67 expression post-neoadjuvant chemotherapy (NAC) on patient outcome. 110 patients were treated with NAC between 2002 and 2011). All patients had clinical stage IIB-IIIB breast cancer. Pathological complete response (pCR) was defined as absence of invasive tumour cells in the breast and axillary lymph nodes. Median cut-off value of 15% was used to define Ki-67 expression as high and low. ER positivity was defined as >10% positive tumour cell staining. Patients received mean of 4 courses of NAC which were mainly anthracycline-based. Breast conserving surgery (BCS) was carried out in 40%, and pCR rate was 5.45%. Tumour downsizing was achieved in 66%, and 57% of the patient had axillary metastasis. The median Ki-67 expression changed from 25 to 14% after NAC. 39/84 patients (46%) who had high Ki-67 expression had reduced to low Ki-67 expression. 82 patients were ER positive prior to NAC, and 2/82 became ER negative after NAC. 77 patients were PR positive prior to NAC, and 10/77 became PR negative after NAC. On multivariate analysis, post-NAC Ki-67 level >15%, ER and PR expression, high tumour grade, and triple negative status significantly influence disease free survival (DFS). Based on this information, three groups were generated; ER positive and low Ki-67 expression post-NAC, ER negative and high Ki-67 expression post-NAC, and ER negative or high Ki-67 expression post-NAC. Improved DFS was observed in the group who were ER positive and low Ki-67 expression post-NAC. Poor DFS was observed in the group who were ER negative and high Ki-67 expression post-NAC.
European Journal of Surgical Oncology 2013; DOI; 10.1016/j.ejso.2013.06.024
Subfascial harvest during lat dorsi flap breast reconstruction significantly improves back donor-site morbidity
Widespread adoption of the extended latissimus dorsi myocutaneous flap in breast reconstruction has been limited by donor-site complications. The dissection plane may be either above or below the superficial layer of the thoracolumbar fascia, which may be transferred with the flap or retained on the back skin flaps. The aim of this study was to investigate whether varying the plane of dissection improves donor-site morbidity and complications. A comparative analysis of consecutive women treated with extended latissimus dorsi myocutaneous breast reconstruction by a single surgeon (D.F.) between 2006 and 2012 was performed. Eighty patients were reviewed. Between 2006 and 2011, 47 patients were treated with traditional suprafascial harvest (group A); the subsequent 33 patients between 2011 and 2012 had subfascial harvest (group B), retaining the superficial fascia on the back skin flaps. When compared with group A, group B patients showed significant reduction in both mean number of seroma drainage events (p = 0.027) and mean total aspirated seroma volume, which was reduced by half (p = 0.006). Group B patients also reported significant reduction in donor-site pain (p = 0.041) and donor-site scar adherence to the chest wall (p = 0.026). No increases in flap or donor-site dehiscence, partial flap loss, or other minor or major complications were observed.
Plastic and Reconstructive Surgery;2013: doi: 10.1097/PRS.0b013e31829fe4f6
Some studies have suggested that night work may be associated with an increased risk of breast cancer in nurses. Authors aimed to explore the role of circadian gene polymorphisms in the susceptibility to night work-related breast cancer risk. Authors conducted a nested case-control study of Norwegian nurses comprising 563 breast cancer cases and 619 controls within a cohort of 49,402 Norwegian nurses ages 35 to 74 years. Authors studied 60 single-nucleotide polymorphisms (SNPs) in 17 genes involved in the regulation of the circadian rhythm in cases and controls. The data were analyzed in relation to the two exposure variables "maximum number of consecutive night shifts ever worked" and "maximum number of consecutive night shifts worked for at least 5 years." The odds of breast cancer associated with each SNP was calculated in the main effects analysis and in relation to night shift work. In the main effects analysis, CC carriers of rs4238989 and GG carriers of rs3760138 in the AANAT gene had increased risk of breast cancer, whereas TT carriers of BMAL1 rs2278749 and TT carriers of CLOCK rs3749474 had reduced risk. The associations were found to be noteworthy using both the FPRP and BFDP tests. With regard to the effect of polymorphisms and night work, several significant associations were observed. After applying FPRP and BFDP in women with at least four night shifts, an increased risk of breast cancer was associated with variant alleles of SNPs in the genes AANAT (rs3760138, rs4238989), BMAL1 (rs2290035, rs2278749, rs969485) and ROR-b (rs3750420). In women with three consecutive night shifts, a reduced risk of breast cancer was associated with carriage of variant alleles of SNPs in CLOCK (rs3749474), BMAL1 (rs2278749), BMAL2 (rs2306074), CSNK1E (rs5757037), NPAS2 (rs17024926), ROR-b (rs3903529, rs3750420), MTNR1A (rs131113549) and PER3 (rs1012477).
Breast Cancer Research 2013; doi:10.1186/bcr3445
This study examines the risk of locoregional recurrence (LRR) after accelerated partial breast irradiation (APBI) for patients who underwent breast conserving surgery (BCS). This technique has the potential advantages of lower radiation dose to tissues outside the treatment volume, and the convenience of shorter treatment duration. This included 277 patients with early-stage invasive breast cancer. With median follow-up of 61 months, 5-year overall and disease free survival of 92.8% and 92.4% were observed. A total of 13 patients suffered from LRR with a 5-year LR control rate of 94.4%. Univariate analysis showed that ER negative status was significantly associated with LRR (p<0.005), as well as the presence of extensive intraductal component (EIC) (p=0.04) and lymphovascular invasion (p=0.016). Multivariate analysis showed that ER negativity (HR of 12.4; p<0.005), lobular subtype (HR of 9.9; p=0.01), and the presence of EIC (HR of 4.8; p=0.025) or LVI (HR of 5; p=0.02) were independently associated with an increased risk of LRR.
Annals of Surgical Oncology 2013; DOI; 10.1245/s10434-013-3015-5
This study evaluates locoregional outcome in early-stage, node-negative triple negative breast cancer (TNBC) patients treated with either mastectomy or breast conserving surgery (BCS). The cohort included 646 patients with T1-2N0 TNBC available for analysis. 69% of patients underwent BCS and 31% underwent mastectomy. 87% underwent sentinel node biopsy alone versus 13% who underwent axillary lymph node dissection (ALND). The median age at diagnosis was 54 years old. 81% of the patients received adjuvant chemotherapy. BCS group were older (p<0.001), non-black race (p=0.04), less likely to have lymphovascular invasion (p=0.042), and had lower tumour stage (p=0.023). Patients receiving BCS were also less likely to undergo ALND (p<0.001) and have BRCA mutations (p<0.001). Median follow-up was 76.4 months (79.7 months for BCS group versus 77.1 months for mastectomy group). 33 LRR occurred in total with crude LRR rate of 5.3% (4.5% in the BCS group versus 6.6% in the mastectomy group). At univariate analysis there was no difference in the LRR between the two groups (HR 1.5; 95% CI of 0.75-3.01, p=0.25), and similar findings were detected after multivariate regression analysis (OR 1.44; 95% CI 0.71-2.92; p=0.31). 52 distant recurrences (8%) were detected (8% in the BCS group versus 8.1% in the mastectomy group). Uni- and multivariate analysis showed no difference between the two groups (HR=0.97; 95% CI of 0.54-1.75; p=0.92).
Annals of Surgical Oncology 2013; DOI; 10.1245/s10434-013-3011-9
This study investigates patient-reported satisfaction using the BREAST-Q in a cohort of unilateral breast cancer patients who did or did not pursue contralateral prophylactic mastectomy (CPM) with implant reconstruction. This included a cohort of patients who underwent CPM within 1 year of undergoing mastectomy for initial breast cancer diagnosis. 688/3874 eligible patients (18%) pursued CPM from 2000 to 2007. 294 patients completed BREAST-Q; 112 patients underwent CPM with immediate implant reconstruction (IR) and 182 patients underwent immediate IR without CPM. Women choosing CPM were younger (mean 47 versus 50 years old; p=0.001), have white ethnic origin (98.2% versus 86.2%; p=0.001), married (83.9% versus 71.4%; p=0.015), and have family history of breast cancer (59.8% versus 44.4%; p=0.011). Patients in the CPM group also were more likely to undergo gene testing (30.4% versus 17.6%; p=0.011) and harbour BRCA1/2 mutation (29.4% versus 3.2%; p=0.005). Patient’s clinicopathological characteristics and receipt of adjuvant treatment did not differ between the two groups. Minor and major complication rates also did not differ between the two groups. Median time to completion of BREAST-Q from initial mastectomy was 51.9 months in the CPM group, compared to 52.7 months in the non-CPM group. Patients having CPM had significantly higher mean score for satisfaction with breasts (64.4% versus 54.9%; p<0.001), and satisfaction with outcome (74.8% versus 67.7%; p=0.007) 4.3 years after mastectomy. Other HR-QoL domains (psychosocial well-being, physical well-being, and sexual well-being) did not differ. On multivariate analysis, only CPM and absence of lymphoedema were independent predictors with satisfaction with breasts. Similarly, only absence of lymphoedema and having nipple reconstruction were independent predictors of satisfaction with outcome.
Annals of Surgical Oncology 2013; DOI; 10.1245/s10434-013-3026-2
This study evaluates outcome in patients treated with B Technique (otherwise known as Grisotti flap) for central breast cancer. The study cohort included 70 patients between 1997 and 2008. The mean patient age was 62.3 years old. 27.1% of the cohort was diagnosed with DCIS only, whilst the remaining patients were diagnosed with invasive carcinoma with or without DCIS. The mean tumour size was 16.9mm. Positive resection margin was found in 12/70 patients (17.1%). 10/12 underwent further surgery, and the remaining 2 patients did not required further surgery since the involved margin was posterior. 9/10 patients who underwent second surgery required mastectomy. Follow-up data was available for 38 patients who did not require a re-excision, and with median follow-up of 61.4 months, no local recurrence was detected. 4 patients (5.7%) suffered from partial flap necrosis and 1 patient with wound dehiscence (1.4%). All required further surgical procedures. Cosmetic evaluation and patient questionnaire were completed at least 6 months after radiotherapy to the breast using a modified EORTC questionnaire. 41 patients returned the questionnaire, with 89.8% of women stating the result of their surgery as ‘good’ or ‘very good’. 87.2% of patients stated no change or minimal change in terms of physical awareness. 89.5% of patients reported no or little influence on their sexuality. 13 out of 39 (33.3%) patients required external prosthesis to achieve symmetry. 83% of the patients were satisfied with the shape of the treated breast. Only 10.5% of the women underwent nipple-areolar complex reconstruction.
Annals of Surgical Oncology 2013; DOI; 10.1245/s10434-013-3030-6
Biomarkers to improve the risk—benefit of extended adjuvant endocrine therapy for late recurrence in patients with oestrogen-receptor-positive breast cancer would be clinically valuable. Authors compared the prognostic ability of the breast-cancer index (BCI) assay, 21-gene recurrence score (Oncotype DX), and an immunohistochemical prognostic model (IHC4) for both early and late recurrence in patients with oestrogen-receptor-positive, node-negative (N0) disease who took part in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) clinical trial. In this prospective comparison study, authors obtained archival tumour blocks from the TransATAC tissue bank from all postmenopausal patients with oestrogen-receptor-positive breast cancer from whom the 21-gene recurrence score and IHC4 values had already been derived. BCI analysis in matched samples was carried out with sufficient residual RNA using two BCI models—cubic (BCI-C) and linear (BCI-L)—using previously validated cutoffs. Authors assessed prognostic ability of BCI for distant recurrence over 10 years (the primary endpoint) and compared it with that of the 21-gene recurrence score and IHC4. Study also tested the ability of the assays to predict early (0—5 years) and late (5—10 years) distant recurrence. Suitable tissue was available from 665 patients with oestrogen-receptor-positive, N0 breast cancer for BCI analysis. The primary analysis showed significant differences in risk of distant recurrence over 10 years in the categorical BCI-C risk groups (p<0·0001) with 6·8% (95% CI 4·4—10·0) of patients in the low-risk group, 17·3% (12·0—24·7) in the intermediate group, and 22·2% (15·3—31·5) in the high-risk group having distant recurrence. The secondary analysis showed that BCI-L was a much stronger predictor for overall (0—10 year) distant recurrence compared with BCI-C (interquartile HR 2·30 [95% CI 1·62—3·27]; LR-Δχ2=22·69; p<0·0001). When compared with BCI-L, the 21-gene recurrence score was less predictive (HR 1·48 [95% CI 1·22—1·78]; LR-Δχ2=13·68; p=0·0002) and IHC4 was similar (HR 1·69 [95% CI 1·51—2·56]; LR-Δχ2=22·83; p<0·0001). All further analyses were done with the BCI-L model. In a multivariable analysis, all assays had significant prognostic ability for early distant recurrence (BCI-L HR 2·77 [95% CI 1·63—4·70], LR-Δχ2=15·42, p<0·0001; 21-gene recurrence score HR 1·80 [1·42—2·29], LR-Δχ2=18·48, p<0·0001; IHC4 HR 2·90 [2·01—4·18], LR-Δχ2=29·14, p<0·0001); however, only BCI-L was significant for late distant recurrence (BCI-L HR 1·95 [95% CI 1·22—3·14], LR-Δχ2=7·97, p=0·0048; 21-gene recurrence score HR 1·13 [0·82—1·56], LR-Δχ2=0·48, p=0·47; IHC4 HR 1·30 [0·88—1·94], LR-Δχ2=1·59, p=0·20).
The Lancet Oncology;2013: doi:10.1016/S1470-2045(13)70387-5
PIP silicone breast implants: Rupture rates based on the explantation of 676 implants in a single surgeon series
This study reports the rupture rate of PIP implants based on the explantation of 676 implants in 338 patients (1999 to 2007). All patients underwent surgery using an inframammary incision and 166 patients underwent pre-operative USS. Mean time to implant removal was 7.8 years (range 1-13 years). 144 implants were found to be ruptured in 119 patients resulting in a rupture rate of 35.2% per patient and 21.3% per implant. Significantly higher rupture rate was observed for implants inserted from 2003 (39.2%), compared to prior to 2003 (21.3%; p<0.001). A significantly higher rupture rate was observed in patients who had implants inserted in the sub-pectoral pocket (42%), compared to sub-glandular pocket (26.2%; p<0.001). Pre-operative USS had sensitivity of 90.6% and specificity of 98.3% in diagnosing implant rupture (PPV of 95.1% and NPV of 96.7%). 47/160 patients (29.4%) silicone infiltration of axillary lymph nodes on USS where 41/47 patients had proven implant rupture at the time of explantation. Out of the 338 patients, 2 required additional surgery due to haematoma and three patients were treated for infection.
Journal of Plastic and Reconstructive Surgery 2013; DOI; 10.1016/j.bjps.2013.05.003
This study reports the use of contrast-enhanced MRI to assess the extent of DCIS and whether the microvascularity pattern in DCIS correlates with MR enhancement. 85 cases of DCIS were evaluated with MRI scan (2008 to 2010). The mean patient age was 58 years old and all had clinically non-palpable lesions. 77 cases were pure DCIS, and 8 were microinvasive DCIS where one or more invasive foci smaller than 1mm were detected. Two experienced radiologists reported the MRI where the largest lesion size, enhancement distribution, and the time-intensity curve. Breast conserving surgery was performed in 69 cases and mastectomy in 16 cases. Pathological evaluation was performed by an experienced pathologist blinded to the MRI findings. 45 cases were BIRADS 4, 35 cases BIRAD 5, and in 5 cases no mammographic findings were observed. Contrast enhancement was observed in 59/85 cases (70%). The enhancement morphology was non-mass like in 46/59 cases (78%). On mammogram 74% of DCIS appeared as microcalcifications, and on MRI 70% of DCIS showed enhancement. The mean histopathological size of DCIS was 16.88mm. An excellent agreement was observed between MRI DCIS extent and histopathological tumour size (ICC of 0.77). The mean size of non-enhancing DCIS was 11.24mm versus 19.27mm for enhancing DCIS. 24 patients from the cohort were further selected for immunohistochemistry to determine the pattern of microvascularity. Diffuse pattern was observed in 19/24 cases, which correlated with the MRI enhancement distribution (p=0.036). DCIS size was related to the number of microvessels, and the mean area of vascularity in DCIS positively correlated with the van Nuys score (p=0.02).
The Breast Journal 2013; DOI; 10.1111/tbj.12135
This study investigates factors that influence positive margins for breast conserving surgery (BCS), with a focus on DCIS volume with margin status. 358 patients who had DCIS diagnosed in the final pathology were diagnosed between 1999 to 2009. The volume of DCIS was defined by pathologists as volume of DCIS versus volume of invasive disease on any given slide. The volumes were categorised into 0-25% (83%), 26-50% (8%), and >50% (9%). Margin positivity was defined by the presence of in situ (n=63) or invasive malignancy (n=61) at any margin, and was present in 38% (n=137). The volume of DCIS correlated positively with involved margins (p<0.00001). For tumours with <25% DCIS volume, 67% had negative margins. For tumours with 26-50% DCIS volume, 41% had negative margins. For tumours with >50% DCIS volume, only 30% had negative margins. Positive ER status was associated with a lower volume of DCIS (p=0.026). The volume of DCIS did not correlate with other clinico-pathological parameters. Final re-excision showed residual disease in 48% where a trend was seen with increasing DCIS volume and the risk of residual disease (p=0.061).
Journal of Surgical Research; DOI; 10.1016/j.jss.2013.03.071
This non-randomised, interventional, open-labelled clinical trial evaluates outcome in patients who undergo implant augmentation. This study included 4412 patients with 8811 breast implants (mean follow-up of 3 years). 93.9% of the implants used were textured. Capsular contracture occurred in 317 cases (3.6%). The risk of capsular contracture was higher with axillary (RR of 2.2; p<0.001) and periareolar incisions (RR of 1.9; p<0.001) versus inframammary fold incision. However, the associations were no longer significant on multivariate analysis. The risk of capsular contracture was also lower with subpectoral placement compared to subglandular placement (RR of 0.45; p<0.001). The risk of capsular contracture was also lower with textured devices silicone filled devices (RR of 0.35; p<0.001) and textured highly-cohesive silicon filled devices (RR of 0.16; p<0.001) versus smooth devices. With subglandular placement, risk of capsular contracture was higher with periareolar versus subglandular placement (RR of 1.93; p<0.01). Similarly textured silicon-filled devices and highly cohesive silicon-filled devices had lower risk of capsular contracture compared to smooth devices (RR of 0.25 and 0.18 respectively; p<0.001). With subpectoral placement, risk of capsular contracture was higher with axillary incision (RR of 2.42; p<0.01) versus inframammary incision. Again textured silicon-filled devices and highly cohesive silicon-filled devices had lower risk of capsular contracture compared to smooth devices (RR of 0.42 and 0.16 respectively; p<0.01 and p<0.001). The risk of malposition was higher using axillary incision (RR of 3.72; p<0.001) and periareolar incisions (RR 1.62; p<0.05) versus inframammary fold incision. The risk of malposition was reduced with subpectoral versus subglandular placement (RR of 0.68; p<0.05), and with textured devices versus smooth devices (RR of 0.29; p<0.001). Secondary procedures included capsulectomy or capsulotomy (3.2%), mastopexy (1.5%), reposition (1%), seroma or haematoma aspiration (0.3%), and explantation (5.7%). The risk of secondary procedure was higher with axillary (RR of 1.9; p<0.01) and periareolar (RR of 1.47; p<0.001) incisions versus inframammary incisions. Implant pocket position was not associated with increased risk of secondary procedures. However, the risk of secondary procedure was reduced with textured devices (RR of 0.48; p<0.001) versus smooth devices.
Journal of Plastic, Reconstructive & Aesthetic Surgery 2013; DOI; 10.1016/j.bjps.2013.04.046
This study reports the use of skin-reducing mastectomy and one-stage implant reconstruction using an inferior dermal sling (2008-2012). In this technique suturing the free edge of pectoralis major to the raised dermal flap creates a myodermal pocket for implant insertion. The cohort included 64 patients who underwent 104 mastectomies with median age of 49 years old. 25/64 patients had risk-reducing bilateral prophylactic mastectomies. The median implant size used was 420cc. One patient developed haematoma post-operatively and eventually had explantation. 2 patients had extensive skin flap necrosis resulting in explantation. Another patient developed peri-implant infection resulting in explantation. The overall explantation rate was 6.3% in patients (3.8% of breasts). Minor skin necrosis was observed in 10 breasts, which were treated conservatively. Superficial wound infection was observed in 8 breasts, all of whom were managed conservatively with antibiotics. Seroma was observed in 6 patients and treated conservatively. With median follow-up of 35 months, one patient developed capsular contracture that required explantation at 12 months. 16 patients had post-mastectomy radiotherapy and 12 patients had adjuvant chemotherapy.
Journal of Plastic, Reconstructive & Aesthetic Surgery 2013; DOI; 10.1016/j.bjps.2013.04.048
Associations between circulating concentrations of oestrogens, progesterone, and androgens with breast cancer and related risk factors in premenopausal women are not well understood. Authors aimed to characterise these associations with a pooled analysis of data from seven studies. Individual participant data for prediagnostic sex hormone and sex hormone-binding globulin (SHBG) concentrations were contributed from seven prospective studies. Authors restricted analyses to women who were premenopausal and younger than 50 years at blood collection, and to women with breast cancer diagnosed before age 50 years and estimated odds ratios (ORs) with 95% CIs for breast cancer associated with hormone concentrations by conditional logistic regression in cases and controls matched for age, date of blood collection, and day of cycle, with stratification by study and further adjustment for cycle phase. Authors examined associations of hormones with risk factors for breast cancer in control women by comparing geometric mean hormone concentrations in categories of these risk factors, adjusted for study, age, phase of menstrual cycle, and body-mass index (BMI). All statistical tests were two-sided. Data for up to 767 women with breast cancer and 1699 controls were included in the risk analyses. Breast cancer risk was associated with a doubling in concentrations of oestradiol (OR 1·19, 95% CI 1·06—1·35), calculated free oestradiol (1·17, 1·03—1·33), oestrone (1·27, 1·05—1·54), androstenedione (1·30, 1·10—1·55), dehydroepiandrosterone sulphate (1·17, 1·04—1·32), testosterone (1·18, 1·03—1·35), and calculated free testosterone (1·08, 0·97—1·21). Breast cancer risk was not associated with luteal phase progesterone (doubling in concentration OR 1·00, 95% CI 0·92—1·09), and adjustment for other factors had little effect on any of these ORs. Cross-sectional analyses in control women showed several associations of sex hormones with breast cancer risk factors.
The Lancet Oncology 2013; doi:10.1016/S1470-2045(13)70301-2
NAC can downstage the nodal tumour burden in the axilla. This study examines if the degree of lymph node involvement after NAC correlates with the incidence of lymphoedema. Perometer was used to assess arm volume at 3 to 7 months intervals after surgery (median follow-up 25 months). Lymphoedema was defines as relative volume change>10%. There were two groups in the study who had axillary nodal metastasis; patients who received NAC (n=68) versus adjuvant chemotherapy (n=161). In the NAC group, 87% had partial response in the axilla and 13% had complete pathological response. Lymphoedema was diagnosed in 15% of the NAC group versus 23% in the adjuvant group. Univariate analysis of all patients showed that high BMI (p<0.0001) was a significant predictive factor. Analysis of NAC group showed that, at univariate analysis, having residual lymph node disease after chemotherapy was the only significant factor with a nine-fold increase risk in the development of lymphoedema (p=0.038, HR=9.04; CI, 1.13-72.19).
Annals of Surgical Oncology 2013; DOI; 10.1245/s10434-012-2828-y
This study examines the incidence of post-mastectomy venous thromboembolism (VTE) investigates for potential predictive factors that could have clinical utility. The American College of Surgeons National Surgical Quality Improvement Program(ACS-NSQIP) database (n=49208) was used (2005-2009). Patient factors examined included; age, race, BMI, smoking, co-morbidities, adjuvant treatment, presence of venous catheter, operative time, and whether immediate breast reconstruction (IBR) was performed. The diagnosis of pulmonary embolus (PE) and deep vein thrombosis (DVT) was made within 30 days after surgery. The incidence rate of VTE was 0.27% (n=114). PE was diagnosed in 47/114 cases. Patients with BMI>30 had greater risk of VTE compared to BMI<30 (50% vs. 34%; p<0.001). Venous catheter placement (p=0.02), inpatient status (p<0.001), operative time >3 hours (49% vs. 18%; p<0.001), and IBR (44% vs. 19%; p<0.001) were all associated with increased risk of VTE. Multivariate analysis showed that BMI>30 (OR 2.02; p<0.001), inpatient status (OR 2.36; p<0.001), venous catheter placement (OR 2.2; p=0.045), and operative time >3 hours (OR 2.42; p<0.001) remained significant.
The Breast 2013; DOI; 10.1016/j.breast.2013.04.018
Subcutaneous trastuzumab has shown non-inferior efficacy and a similar pharmacokinetic and safety profile when compared with intravenous trastuzumab in patients with HER2-positive early breast cancer. Authors assessed patient preference for either subcutaneous or intravenous trastuzumab in the international, randomised PrefHer study. Eligible patients were women aged 18 years or older with HER2-positive, histologically confirmed primary invasive breast adenocarcinoma, no evidence of residual, locally recurrent, or metastatic disease after completion of surgery and chemotherapy (neoadjuvant or adjuvant).Radiotherapy or hormone therapy was allowed. Patients were randomised (randomly permuted blocks of four) to receive four cycles of 600 mg fixed-dose subcutaneous adjuvant trastuzumab via a single-use injection device or hand-held syringe followed by four cycles of standard intravenous trastuzumab, or the reverse sequence. The primary endpoint was the proportion of patients indicating an overall preference for subcutaneous or intravenous trastuzumab, assessed by patient interview in the evaluable intention-to-treat (ITT) population (patients who completed both interviews and had at least one administration of both subcutaneous and intravenous trastuzumab). 124 patients were randomly allocated to receive subcutaneous followed by intravenous trastuzumab, and 124 to receive the reverse sequence. 117 patients in the subcutaneous first group and 119 in the intravenous first group were included in the evaluable ITT population. Subcutaneous trastuzumab via the single-use injection device was preferred by 216 patients (91·5%, 95% CI 87·2—94·7; p<0·0001). Only 16 patients preferred intravenous trastuzumab (6·8%, 3·9—10·8), and four had no preference (1·7%, 0·5—4·3). Clinician-reported adverse events occurred in 141 of 242 (58%) patients during the pooled subcutaneous periods and 105 of 241 (44%) patients during the pooled intravenous periods; seven (3%) and five (2%) were grade 3, no patients had a grade 4 or 5 event. The most common grade 3 adverse event was influenza (0·8% patients).
The Lancet Oncology; 2013: doi:10.1016/S1470-2045(13)70383-8
This study examines outcome in young women with early breast cancer who suffer from local recurrence (LR) and investigates potential predictive factors (1988-2005). 937 patients under 40 years old underwent WLE, and 20% had developed recurrence at a median follow-up of 9.5 years. The median age at diagnosis of LR was 43 years old, and the median time from surgery to diagnosis of LR was 5.7 years. 34/124 LRs were diagnosed on imaging alone. 105/124 was diagnosed with invasive recurrence rather than in situ recurrence. 109/124 was diagnosed with recurrence at or near the site of the tumour. 121 patients underwent completion mastectomy, and 59 patients received adjuvant systemic therapy. 5- and 10-year distant-recurrence free survival rates were 73% and 61% respectively, with equivalent overall survival of 90% and 73%. Multivariate analysis showed that LR measuring greater than 2cm had worse distant-recurrence free survival (HR 2.88; p=0.007).
EJSO 2013. DOI: 10.1016/j.ejso.2013.05.004
This study examines the relationship between breast cancer subtypes (BCS) and axillary nodal metastasis, and determines if ant correlations exist between BCS and other clinico-pathological factors. The study (n=453) includes patients with stage I and II breast cancer patients who underwent WLE. Luminal A subgroup consisted of 48.5%, luminal B 16.1%, HER2 11%, and triple negative (TN) 24.3%. Triple negative and HER2 presented at younger age (47.9 years old and 48 years old respectively; p<0.001)) versus luminal A and B subtypes (53.5 years old and 53 years old). Patients who received chemotherapy were more often TN (70.1%) or HER2 (74.5%) versus luminal A and B subtypes (64.1% and 71.6%; p<0.001). There were no significant correlation between BCS and lymph node involvement. However, T2/3 tumours were more often seen in TN subtypes (44.3%), compared to HER2 (36.2%) or luminal A (20.2%) and B (26.5%) subtypes (p<0.001). Multivariate analysis showed that BCS was significantly associated with T stage (p=0.011), race (p<0.001), age (p<0.001), and methods of detection (p<0.001). For overall survival, mean-survival time was 4.9 years for TN, 7 years for HER2, 18.6 years for luminal A, and 16.7 years for luminal B.
Annals of surgical oncology 2013, DOI: 10.1245/s10434-013-2994-6
The addition of bevacizumab to chemotherapy improves progression-free survival in metastatic breast cancer and pathological complete response rates in the neoadjuvant setting. Micrometastases are dependent on angiogenesis, suggesting that patients might benefit from anti-angiogenic strategies in the adjuvant setting. Authors therefore assessed the addition of bevacizumab to chemotherapy in the adjuvant setting for women with triple-negative breast cancer. Authors randomly allocated patients aged 18 years or older (1:1 with block randomisation; stratified by nodal status, chemotherapy [with an anthracycline, taxane, or both], hormone receptor status [negative vs low], and type of surgery) to receive a minimum of four cycles of chemotherapy either alone or with bevacizumab (equivalent of 5 mg/kg every week for 1 year). The primary endpoint was invasive disease-free survival (IDFS). Efficacy analyses were based on the intention-to-treat population, safety analyses were done on all patients who received at least one dose of study drug, and plasma biomarker analyses were done on all treated patients consenting to biomarker analyses and providing a measurable baseline plasma sample. 1290 patients were randomized to receive chemotherapy alone and 1301 to receive bevacizumab plus chemotherapy. Most patients received anthracycline-containing therapy; 1638 (63%) of the 2591 patients had node-negative disease. At the time of analysis of IDFS, median follow-up was 31·5 months (IQR 25·6—36·8) in the chemotherapy-alone group and 32·0 months (27·5—36·9) in the bevacizumab group. At the time of the primary analysis, IDFS events had been reported in 205 patients (16%) in the chemotherapy-alone group and in 188 patients (14%) in the bevacizumab group (hazard ratio [HR] in stratified log-rank analysis 0·87, 95% CI 0·72—1·07; p=0·18). 3-year IDFS was 82·7% (95% CI 80·5—85·0) with chemotherapy alone and 83·7% (81·4—86·0) with bevacizumab and chemotherapy. After 200 deaths, no difference in overall survival was noted between the groups (HR 0·84, 95% CI 0·64—1·12; p=0·23). Exploratory biomarker assessment suggests that patients with high pre-treatment plasma VEGFR-2 might benefit from the addition of bevacizumab (Cox interaction test p=0·029). Use of bevacizumab versus chemotherapy alone was associated with increased incidences of grade 3 or worse hypertension (154 patients [12%] vs eight patients [1%]), severe cardiac events occurring at any point during the 18-month safety reporting period (19 [1%] vs two [<0·5%]), and treatment discontinuation (bevacizumab, chemotherapy, or both; 256 [20%] vs 30 [2%]); we recorded no increase in fatal adverse events with bevacizumab (four [<0·5%] vs three [<0·5%]).
The Lancet Oncology, 2013;doi:10.1016/S1470-2045(13)70335-8
This study evaluates the post-radiofrequency ablation (RFA) cell viability using cytokeratin 8 (CK8) nicotinamide adenine dinucleotide diaphorase (NADHD), with the latter considered to be the gold standard. Postmenopausal patients with unifocal invasive ductal carcinomas were eligible for the study. After lumpectomy or mastectomy, ultrasound was used to localise the tumour, and the needle-electrode was placed in the centre of tumour for 12minutes for RFA. Whole mount sectioning was then performed and as well as H&E staining, immunohistochemistry (IHC) was performed for both CK8 and NADHD. 20 patients were included in the study with average tumour size of 9.8mm, compared to mean histological tumour size of 12mm. A clear demarcation was seen between the viable and non-viable tissue on IHC. In 17 cases, complete loss of viability of the target lesion was achieved. Viable invasive tumour cells were observed in 3 cases however. In 2 cases viable DCIS was found outside the ablated region although the target lesion was destroyed. All patients had clear resection margins.
The Breast 2013; DOI; 10.1016/j.breast.2012.11.004
This study aims to specify the risk of invasive carcinoma after core biopsy of DCIS and to improve the indication to perform a concurrent SLNB in these patients. The study cohort included 205 patients (2006-2010), and patients either had core biopsy (median 4 specimens) or vacuum biopsy (median 12 specimens), which confirmed the presence of DCIS only. Invasive cancer was detected in 37/205 patients (18%). Palpable mass (p<0.001), mass lesion on USS (p<0.001), suspicious non-calcified findings on mammogram (p=0.002), BI-RADS score of 5 (p=0.012), larger lesion diameter (p=0.015), and histological findings >50% ducts affected by carcinoma (p=0.003) correlated with findings of invasive carcinoma. When at least three of the factors were present, the risk of invasion was almost six times as likely (OR 5.91, p<0.001). Multivariate logistic regression also showed that the presence of a palpable mass was the only statistically significant independent predictor of invasive carcinoma (OR=3.71; p=0.008). The probability of invasion was 56% when the two significant factors were combined. Concurrent axilla staging was performed in 118 patients. 28/37 patients diagnosed with eventual invasive carcinoma had concurrent axilla staging, with 9 patients undergoing a second surgical procedure. The hypothetical application of the two significant factors showed that 16 patients could have been spared unnecessary SLNB, and 4 patients could have been correctly recommended concurrent SLNB. Hence 20/205 patients (9.8%) could have benefited.
The Breast 2013; DOI; 10.1016/j.breast.2012.11.002
This study was to determine whether bacterial colonization of drains can be reduced by local antiseptic interventions. After institutional review board approval, patients undergoing total mastectomy and/or axillary lymph node dissection were randomized to standard drain care (control) or drain antisepsis (treated). Standard drain care comprised twice daily cleansing with alcohol swabs. Antisepsis drain care included (1) a chlorhexidine disc at the drain exit site and (2) irrigation of the drain bulb twice daily with dilute sodium hypochlorite (Dakin's) solution. Culture results of drain fluid and tubing were compared between control and antisepsis groups. Overall, 100 patients with 125 drains completed the study with 48 patients (58 drains) in the control group and 52 patients (67 drains) in the antisepsis group. Cultures of drain bulb fluid at 1 week were positive (1+ or greater growth) in 66% (38/58) of control drains compared with 21% (14/67) of antisepsis drains (P = 0.0001). Drain tubing cultures demonstrated more than 50 colony-forming units in 19% (8/43) of control drains versus 0% (0/53) of treated drains (P = 0.004). Surgical site infection was diagnosed in 6 patients (6%)–-5 patients in the control group and 1 patient in the antisepsis group (P = 0.06).
Annals of Surgery, 2013; doi: 10.1097/SLA.0b013e31828c0b85
The Z0011 trial states that for patients with low volume disease in the axilla, completion axillary lymph node dissection (cALND) can be safely omitted. This study examines the exportability of the trial results by examining the outcome in patients who would have met the eligibility criteria of the trial versus those who did not meet the criteria. 188 patients were identified from prospectively maintained databases from 3 institutions. Included patients had clinically negative axilla, had one or more positive SLNs on histological examination. However, 63 patients were excluded since positive SLNs were only identified after immunohistochemistry, resulting in a cohort of 125 patients. Eligible group (n=87) for omitting cALND were identified using the Z0011 criteria. The ineligible group (n=38) had >2 positive SLNs, mastectomy, T3 cancers, and no adjuvant radiotherapy. All patients underwent cALND. Compared to the Z0011 ALND arm, the eligible group had similar clinico-pathological characteristics, apart from greater number of grade 1 cancers in the study cohort (p=0.01). The prevalence of micrometastasis was also lower in the study cohort (p=0.01). The ineligible group had significantly more positive non-SLNs (p=0.01) than the eligible group. With median follow-up time of 72 months, the 5-year overall survival rates were 96% for the eligible group versus 81% for the ineligible group (p<0.0001). The respective 5 year disease-free survival rates were 91% and 69% (p=0.006).
Annals of Surgical Oncology 2013; DOI; 10.1245/s10434-013-2917-6
This study examines the outcome in patients with stage III breast cancer (T3-4 and N1-3) in the setting of neoadjuvant chemotherapy (NAC) versus adjuvant chemotherapy. Excluding patients with inflammatory breast cancer, 166 patients were identified in the NAC group, versus 193 patients in the adjuvant chemotherapy group (2004 to 2007). Mastectomy rate was 56.6% in the NAC group. The clinical American Joint Committee on Cancer (AJCC) stage were similar between the two groups (p=0.3). The proportion of Ki67>14% was higher in the NAC group (p<0.0001). The median follow-up was 66.9 months. The 5-year local recurrence free survival was 93.6% in the NAC group versus 95.9% in the adjuvant chemotherapy group (p=0.108), with respective DFS of 71.9% versus 72.7% (p=0.55). Cox regression model showed that Ki-67 levels predicted local recurrence (HR 2.1; p=0.05). The 5-year local recurrence free survival rate was 96.3% in the mastectomy group, 94.7% in the pre-planned breast conservation surgery (BCS) group, and 90.9% in the downstaged BCS (p=0.669).
Annals of Surgical Oncology 2013; DOI; 10.1245/s10434-013-2909-6
Seroma is a frequent complication after breast cancer surgery. Closed suction drainage for several days is the standard procedure to reduce seroma formation. The aim of this study was to compare the efficacy of external compression dressing, suture flap fixation, and the conventional method of closed suction drains in the prevention of seroma formation. A total of 161 patients were prospectively randomized in a three groups × two subgroups design into control (n = 48), compression dressing (n = 53) and suturing groups (n = 49), and two subgroups, conventional drain removal (n = 75) and early drain removal (n = 75). All patients underwent ALND as part of MRM or BCT. The primary end point was the incidence of seroma. Suture flap fixation significantly reduced the incidence of seroma (p = 0.003), total drain output (p = 0.005), and duration of drainage (p = 0.001) without increase in wound complications. Compression dressing reduced duration of drainage significantly (p = 0.03), but not the total drain output (p = 0.15) or seromas (p = 0.58). Early drain removal on postoperative day 7 irrespective of drain output does not significantly increase seroma formation (p = 0.34) or wound complications. On multivariate analysis, BMI ≥ 30 (p = 0.02) and longer duration of drainage (p = 0.04) were identified as independent predictors for seroma formation.. Compression dressing offers no advantage over normal dressing. Drains can be removed safely on postoperative day 7 irrespective of output without significant increase in complications.
The Breast Journal 2013; DOI: 10.1111/tbj.12164
This study evaluates the use of intraoperative ultrasound-guided excision (IOUS) and intraoperative macroscopic margin assessment. The study was performed between 2007 to 2011 (n=225), and excluded patients with DCIS and those who underwent NAC. Ultrasound was performed pre-operatively to mark the location of the tumour on the skin, and used during the operation to guide the surgeon, and to examine the margin status of the excised tissue. If the margins were macroscopically involved or <3mm from the tumour, further cavity shaves were performed. The mean tumour diameter was 12.1mm, and invasive ductal carcinomas consisted of 84.9% of the cases. In 45.7% (n=103) of the cases, the margins were deemed to be close using IOUS, and hence further cavity shaves were performed in the same setting. In 24/103 cases, residual tumour was present in the cavity shaves, but only 3/24 required a second operation to clear margins. Where sufficient margins were deemed to be achieved using IOUS (n=122), there were 6 false negative cases upon microscopic examination. This resulted in sensitivity of 80% and specificity of 86.6%. Overall, second operation was required in 4% (9/225 cases).
The Breast 2013; 10.1016/j.breast.2012.10.006
This study investigated if standard clinicopathological parameters predicted the results of the Mammaprint (MP), and also the concordance between MP and indications for adjuvant chemotherapy based on the National Comprehensive Cancer Network (NCCN) guidelines and the St. Gallen consensus. All patients had unilateral T1-3, N0-1, M0 breast cancer. MP assay was performed using a 3 mm punch biopsy, and results were expressed as high or low risk. The study involved 124 patients from 2009 to 2010. MP results were available for 106 samples (53 high risk and 53 low risk). High grade (P<0.001), ER (P=0.015) and PR (p=0.004) negativity, Her2 positivity (p=0.001), and Ki67 levels greater than 20% (p<0.001) were significantly associated with high risk MP score. Among ER+ and Her2- patients (n=68), only Ki67 levels significantly predicted MP results after multivariate analysis (OR 3.71; p=0.018). Where the indications for chemotherapy was undetermined along with endocrine therapy, MP results would have led to different treatment decisions in 13/46 cases using NCCN guidelines (28%), and in 20/68 cases using St.Gallen consensus (29%)
The Breast 2013; DOI; 10.1016/j.breast.2013.03.013
Since 2005, 12 months of adjuvant trastuzumab has been the standard treatment for patients with HER2-positive early-stage breast cancer. However, the optimum duration of treatment has been debated. Authors did a non-inferiority trial of a shorter exposure of 6 months versus the standard 12 months of trastuzumab for patients with early breast cancer. This study was an open-label, randomised, phase 3 trial in 156 centres in France. Patients with HER2-positive early breast cancer who had received at least four cycles of chemotherapy, had breast-axillary surgery, and had received up to 6 months of trastuzumab (administered by intravenous infusions over 30—90 min every 3 weeks; initial loading dose 8 mg/kg; 6 mg/kg thereafter) before randomisation were eligible. Patients were randomly assigned via central randomisation procedure with web-based software to continue trastuzumab for another 6 months (12 months total duration; control group) or to discontinue trastuzumab at 6 months (6 months total duration; experimental group). Randomisation was stratified by concomitant or sequential administration of trastuzumab with chemotherapy, oestrogen-receptor status, and centre using a minimisation algorithm. The primary endpoint was disease-free survival, with a prespecified non-inferiority margin of 1·15. 1691 patients were randomly assigned to receive 12 months of trastuzumab and 1693 to receive 6 months of trastuzumab; 1690 patients in each group were included in the intention-to-treat analyses. After a median follow-up of 42·5 months (IQR 30·1—51·6), 175 disease-free survival events were noted in the 12-month group and 219 in the 6-month group. 2-year disease-free survival was 93·8% (95% CI 92·6—94·9) in the 12-month group and 91·1% (89·7—92·4) in the 6-month group (hazard ratio 1·28, 95% CI 1·05—1·56; p=0·29). 119 (93%) of the 128 cardiac events (clinical or based on assessment of left ventricular ejection fraction) occurred while patients were receiving trastuzumab. Significantly more patients in the 12-month group experienced a cardiac event than did those in the 6-month group (96 [5·7%] of 1690 patients vs 32 [1·9%] of 1690 patients, p<0·0001). After 3·5 years follow-up, we failed to show that 6 months of treatment with trastuzumab was non-inferior to 12 months of trastuzumab.
The Lancet Oncology, July;2013:doi:10.1016/S1470-2045(13)70225-0
This study examines the decision-making of breast surgeons and oncologists regarding adjuvant treatment using clinical scenarios from actual patients, and evaluates the impact of a gene-expression profiling assay (Oncotype Dx) on their decision-making process. 50 patients (average age 60.2 years old) with ER positive and lymph node negative breast cancer were analysed. The physicians were blinded to each of the 50 cases. Histopathological features were examined and each case was stratified into low, moderate, and high risk similar to the oncotype Dx stratification. The average tumour size was 16mm, 40/50 cases were pure invasive ductal carcinoma, and lymph node metastasis was absent in 42/50 cases. Her2 status was negative in 45 cases. Oncotype Dx showed low RS in 23 cases, intermediate RS in 24 cases, and high RS in 3 cases. Histopathological stratification was low (n=9), intermediate (n=23), and high (n=18). In 4/23 low risk cases by Oncotype Dx, the surgeons changed the decision on adjuvant treatment, compared to 5/23 for the oncologists. In 13/24 intermediate risk cases by Oncotype Dx, the surgeons changed the decision on adjuvant treatment, compared to 4/24 by the oncologists. In 1/3 high risk cases by Oncotype Dx, the surgeons changed the decision on adjuvant treatment, compared to none by the oncologists. In total, surgeons changed the decision making in 36% versus 18% for the oncologists. Surgeons made the decision to treat with chemotherapy in 52% of the cases, compared to 70% by the oncologists.
The breast journal 2013; DOI; 10.1111/tbj.12099
This study examines if the total tumour load (TTL), as defined by CK19 mRNA copies using OSNA, in positive sentinel node biopsies predicts non-SLN metastasis. The study involved 306 patients with total of 616 SLNs. The entire nodes were examined by OSNA, and all non-SLNs were examined by H&E. 105/108 patients who had positive SLN by OSNA underwent cALND. Additional non-SLN metastasis were detected in 30/105 cases (29%). In 75/105 cases where no addition metastasis was found, 37/75 were due to micrometastasis (49%). In the univariate analysis, TTL was a predictive factor of non-additional axillary metastasis (OR 1.67; p=0.003). This was also proved to be the case in multivariate analysis (OR=1.69; p=0.003). When TTL< 1.2 x105 copies/ul, specificities of 85% and sensitivity of 47% were determined (NPV of 80% and PPV 56%). The area under the curve on the ROC curve analysis was 0.71 for TTL.
European Journal of Surgical Oncology 2013; DOI; 10.1016/j.ejso.2013.03.011
The authors aimed to develop a unifying predictive formula for volume assessment in small to large breasts based on anthropomorphic values. Ten anthropomorphic breast measurements and direct volumes of 108 mastectomy specimens from 88 women were collected prospectively. The authors performed a multivariate regression to build the optimal model for development of the predictive formula. The final model was then internally validated. A previously published formula was used as a reference. Mean (±SD) breast weight was 527.9 ± 227.6 g (range, 150 to 1250 g). After model selection, sternal notch–to-nipple, inframammary fold–to-nipple, and inframammary fold–to–fold projection distances emerged as the most important predictors. The resulting formula (the BREAST-V) showed an adjusted R2 of 0.73. The estimated expected absolute error on new breasts is 89.7 g (95 percent CI, 62.4 to 119.1 g) and the expected relative error is 18.4 percent (95 percent CI, 12.9 to 24.3 percent). Application of reference formula on the sample yielded worse predictions than those derived by the formula, showing an R2 of 0.55.
Plastic & Reconstructive Surgery 2013; doi: 10.1097/PRS.0b013e318290f6bd
PET/CT has a high positive predictive value for detection of axillary metastasis, and hence suggests that pre-NAC SLNB can be omitted in case of an FDG-avid node. When the tumour positive is not removed, response to NAC can be assessed using post-NAC SLNB. When axillary response can be accurately determined, ALND may be omitted when patients have cPR of the axilla. This study examines the accuracy of sequential PET/CTs during NAC to identify patients with cPR of axilla. Inclusion criteria was tumour size >3cm and positive axillary lymph node identified pre-operatively. Patients with inflammatory carcinoma were excluded. All patients underwent baseline PET/CT, and in cases of primary tumour FDG uptake on PET/CT1 and absence of distant metastasis, two additional PET/CT scans were performed during NAC. This study involved 80 patients, where 62 patients underwent PET/CT2, and 77 patients underwent PET/CT3. 59 patients underwent all 3 scans. At surgery, pCR in the axilla was observed in 38%, and 9% were found to have isolated tumour cells or micrometastasis only. Baseline FDG uptake was not associated with axillary response to NAC. Early decrease in the baseline FDG uptake was observed in patients who had axillary pCR (p<0.001 on PET/CT2 and p=0.025 on PET/CT3). The area under ROC curve was 0.8 for PET/CT2 and 0.65 for PET/CT3. A relative decrease >60% on PET/CT2 had specificity of 95% and sensitivity of 48%.
Annals of Surgical Oncology 2013, DOI: 10.1245/s10434-013-2902-0
The definition of adequate margins for breast conservation surgery (BCS) varies across different centres. This study reports outcome using a relatively conservative policy from an institution where re-excision is only performed if a margin is positive (defined as ‘tumour on ink’) or close. 543 patients were identified who underwent BCS between 2001 and 2005 (median follow-up 57.3 months). The re-excision rate was 15.5% (n=84; n=64 for further re-excision and n=20 for mastectomy). The average age between the re-excision group (54.4 years old), and the no re-excision group (57.7 years old) was significantly different (p=0.029). 67% of patients who underwent re-excision had tumour size <2cm in diameter, and majority were invasive ductal carcinomas. The overall rate of local recurrence was 3.5%, and the 5 year disease free survival (DFS) was 94% for the re-excision group versus 97.6% for the no re-excision group (p=0.014). 7/84 patients who underwent re-excision suffered from a local recurrence (8.3%). In comparison, 12 patients (2.6%; p=0.015) suffered from a local recurrence in the no re-excision group (n=459). The 5 year DFS, when mastectomy patients were excluded, were 90.6% in the re-excision group versus 97.4% in the no re-excision group (p=0.0097). Significantly greater proportion of re-excision group underwent chemotherapy compared to the no re-excision group (43.6% vs. 28.1%; p=0.0175). There were no significant difference between hormone therapy (p=0.094) and radiotherapy (p=0.42) between the two groups. There were no significance differences in ER/PR/HER2 status between the two groups.
Annals of Surgical Oncology 2013, DOI: 10.1245/s10434-012-2831-3
BRCA1/2 mutation carriers with breast cancer are at high risk of contralateral disease. Such women often elect to have contralateral risk-reducing mastectomy (CRRM) to reduce the likelihood of recurrence. This study considers whether CRRM improves overall survival. 105 female BRCA1/2mutation carriers with unilateral breast cancer who underwent CRRM were compared to controls (593 mutation carriers and 105 specifically matched) not undergoing CRRM and diagnosed between 1985 and 2010. Survival was assessed by proportional hazards models, and extended to a matched analysis using stratification by risk-reducing bilateral salpingo-oophorectomy (RRBSO), gene, grade and stage. Median time to CRRM was 1.1 years after the primary diagnosis (range 0.0–13.3). Median follow-up was 9.7 years in the CRRM group and 8.6 in the non-CRRM group. The 10-year overall survival was 89 % in women electing for CRRM (n = 105) compared to 71 % in the non-CRRM group (n = 593); p < 0.001. The survival advantage remained after matching for oophorectomy, gene, grade and stage: HR 0.37 (0.17–0.80, p = 0.008)—CRRM appeared to act independently of RRBSO. CRRM appears to confer a survival advantage. If this finding is confirmed in a larger series it should form part of the counselling procedure at diagnosis of the primary tumour. The indication for CRRM in women who have had RRBSO also requires further research.
Breast Cancer Research and Treatment 2013;DOI: 10.1007/s10549-013-2583-1
This study evaluates the use of hybrid tracer ICG-99mTc-labelled nanocolloid for sentinel lymph node biopsy (SNB) in breast cancer. ICG (indocyanine green), detected by NIR fluorescence, has been shown to have better sentinel lymph node (SLN) identification rate than conventional blue dyes. Patients were divided into high (n=16) and low (n=16) ICG-99mTc-labelled nanocolloid particle density. This was injected intracutaneously in the tumour quadrant. 1ml patent blue dye was also injected around the areola. Hand-held gamma probe and mini-FLARETM imaging system was used to detect SLN. The primary endpoint of the study was the SLN identification rate, and the secondary endpoints were the number of SLNs identified per patient, percentage of tracer accumulation, fluorescence intensity, and fluorescence signal to background ratio of SLNs. The two treatment arms had similar clinico-pathological characteristics. Pre-operative scintigraphy identified at least one SLN per patient. 48 radioactive lymph nodes were detected by NIR fluorescence and the gamma probe, but only 42/48 lymph nodes were stained blue. Histological analysis showed metastasis in 13/32 patients, with macrometastasis seen in 8/13. Doubling the particle density did not result in improvement of fluorescence intensity or signal to background ratio of the SLN.
British Journal of Surgery 2013; DOI; 10.1002/bjs.9159
There is increasing evidence that patients with micrometastasis detected on SNB do not benefit from completion ALND. This study evaluates if the method of detection (screen or symptomatic) has any predictive role in detecting additional positive lymph nodes when SLNs contain micrometastasis. There were 1458 patients who underwent SNB (2001-2011) at a single Swedish centre; 757 patients were screen-detected, and 701 patients were symptomatic. Micrometastasis was detected in 62/757 patients in the screen-detected group, compared to 81/701 patients in the symptomatic group. 3/61 patients who underwent completion ALND in the screen-detected group had further metastasis, compared to 18/79 patients in the symptomatic group (p=0.01). Logistic regression analysis, adjusting for tumour size and grade, showed that odd ratio was 5 for further metastasis in the ALND specimen in the symptomatic group versus the screen-detected group.
European Journal of Surgical Oncology 2013; DOI; 10.1016/j.ejso.2013.03.012
Topoisomerase IIα (Topo IIα) is a DNA binding enzyme, and its gene is located adjacent to the HER-2 gene. Previous studies suggest that its expression may predict anthracycline activity, especially when it is co-amplified with HER-2. This study examines the expression of Topo IIα in patients who were treated with anthracycline-based NAC using immunohistochemistry (n=99). All regimens were anthracycline-based for 3-6 cycles, and all patients underwent mastectomy and ALND within 4 weeks post-NAC. The median duration of patient follow-up was 66 months. Immunohistochemistry was performed for ER, PR, HER-2, Ki-67, and Topo IIα. Pathological complete response was seen in 9/99 patients. Using the RECIST criteria, 66/99 patients were defined to have responded to NAC (partial or complete). Co-expression of HER-2/Topo IIα correlated with response to NAC (p=0.033), which remained significant on multivariate analysis (p=0.042). In HER-2 positive patients (n=81), nodal metastasis (p=0.005), Ki-67 expression (p=0.022), and Topo IIα expression (p=0.007) were independent predictors of DFS. The 5 year DFS was 29.9% for HER2+/Topo IIα - patients, compared to 55.8% for HER-2+/Topo IIα + patients.
European Journal of Surgical Oncology 2013; DOI; 10.1016/j.ejso.2013.02.019
This cross sectional study examined the development of persistent pain after treatment for breast cancer and to examine risk factors associated with continuing pain. All eligible women who underwent surgery for primary breast cancer in Denmark in 2005 and 2006 were surveyed. 2411 (89%) women returned the questionnaire. Prevalence of persistent pain after treatment for breast cancer ranged from 22% to 53% depending on treatment. In 2012, 903 (37%) women reported such pain, a fall from 45% in 2008. Of these, 378 (16%) reported pain of ≥4 on a numerical rating scale (scale 0-10), a fall from 19%. Among women reporting pain in 2008, 36% no longer reported it in 2012. In contrast, 15% of the women who did not report pain in 2008 reported it in 2012. Risk factors for having pain were axillary lymph node dissection rather than sentinel lymph node biopsy (odds ratio 2.04, 95% confidence interval 1.60 to 2.61; P<0.001) and age ≤49 (1.78, 1.25 to 2.54; P<0.001). No particular method of treatment or age was associated with an increase in pain from 2008 to 2012.
BMJ 2013; doi: http://dx.doi.org/10.1136/bmj.f1865
For women with ductal carcinoma in situ (DCIS) of the breast, the risk of developing an ipsilateral breast event (IBE; defined as local recurrence of DCIS or invasive carcinoma) after surgical excision without radiation is not well defined by clinical and pathologic characteristics. The Oncotype DX breast cancer assay was performed for patients with DCIS treated with surgical excision without radiation in the Eastern Cooperative Oncology Group (ECOG) E5194 study. The association of the prospectively defined DCIS Score (calculated from seven cancer-related genes and five reference genes) with the risk of developing an IBE was analyzed using Cox regression. There were 327 patients with adequate tissue for analysis. The continuous DCIS Score was statistically significantly associated with the risk of developing an IBE (hazard ratio [HR] = 2.31, 95% confidence interval [CI] = 1.15 to 4.49; P = .02) when adjusted for tamoxifen use (prespecified primary analysis) and with invasive IBE (unadjusted HR = 3.68, 95% CI = 1.34 to 9.62; P = .01). For the prespecified DCIS risk groups of low, intermediate, and high, the 10-year risks of developing an IBE were 10.6%, 26.7%, and 25.9%, respectively, and for an invasive IBE, 3.7%, 12.3%, and 19.2%, respectively (both log rank P ≤ .006). In multivariable analyses, factors associated with IBE risk were DCIS Score, tumor size, and menopausal status (all P ≤ .02).
Journal of National Cancer Institute; doi: 10.1093/jnci/djt067
Breast cancer at a young age is associated with poor prognosis. The Prospective Study of Outcomes in Sporadic and Hereditary Breast Cancer (POSH) was designed to investigate factors affecting prognosis in this patient group. Between 2000 and 2008, 2956 patients aged 40 years or younger were recruited to a UK multicenter prospective observational cohort study (POSH). Details of tumor pathology, disease stage, treatment received, and outcome were recorded. Median age of patients was 36 years. Median tumor diameter was 22mm, and 50% of patients had positive lymph nodes; 59% of tumors were grade 3, 33.7% were estrogen receptor (ER) negative, and 24% were human epidermal growth factor receptor 2 (HER2) positive. Five-year OS was higher for patients with ER-positive than ER-negative tumors (85.0%, 95% confidence interval [CI] = 83.2% to 86.7% vs 75.7%, 95% CI = 72.8% to 78.4%; P < .001), but by eight years, survival was almost equal. The eight-year OS of patients with ER-positive tumors was similar to that of patients with ER-negative tumors in both HER2-positive and HER2-negative subgroups. The flexible parametric survival model for OS shows that the risk of death increases steadily over time for patients with ER-positive tumors in contrast to patients with ER-negative tumors, where risk of death peaked at two years.
Journal of the National Institue of Cancer 2013: doi: 10.1093/jnci/djt134
This study examines the effectiveness of Sapylin (OK-432) in reducing seroma formation after axillary LN dissection. This was a randomised control trial blinded 54 patients to OK-432 and 57 to controls. The mean total drainage was lower in the experimental group (325ml versus 362ml; p=0.008), and had shorter duration of axillary drainage (4.52 days versus 5.16 days; p=0.003). One week after discharge, 10 patients in the experimental group developed palpable seroma in the experimental group versus 28 in the control group (p=0.001). Experimental group also had fewer seroma aspirations (1 versus 4; p<0.001). There were no adverse effects specific to sapylin compared to the control group.
Annals of Surgical Oncology 2013; doi: 10.1245/s10434-012-2728-1
This prospective cohort study of 104 consecutive mastectomies (47 with immediate latissimus dorsi flaps) examined the effects of latissimus dorsi flap reconstruction on the recovery of shoulder motion and other postsurgical problems. There was a 30 percent decrease of shoulder range of motion 1 month after surgery, with gradual recovery over time. However, mean abduction and flexion capacities did not reach baseline levels and were on average 5 to 10 percent lower than baseline, even after 1 year. Over time, the latissimus dorsi flap was not associated with restriction of flexion or abduction. Scar enlargement (at the first month, p = 0.009) and tissue adhesion (at month 12, p = 0.032) were significantly less common in the latissimus dorsi flap group.
Plastic & Reconstructive Surgery, 2013; doi: 10.1097/PRS.0b013e31828659de
This study compares immediate free flap reconstruction following NAC (n=33) versus the same procedure without neaoadjuvant chemo (NAC, n=62) between 2006 and 2012. The median age in the NAC group was 46.5 years old, and in the control group 49 years old. The median BMI was higher in the NAC group (28.5 versus 25; p=0.0035). Both groups were similar in terms of clinico-pathological characteristics. Although there were more smokers in the NAC group (26.7% versus 12.3%), the differences were not significant. 20 patients in the NAC group had one or more complications, compared to 37 patients in the control group (p=0.87). 5 patients in each group required further surgery due to complications (p=0.3). In the NAC group, obesity (p=0.016) and smoking status (p=0.014) were significantly associated with complications. In the NAC group, radiotherapy was administered in 27 patients, where delay occurred in 3 patients. This was opposed to delay in 3 out of 36 patients in the control group (p=1).
European Journal of Surgical Oncology, 2013; doi: 10.1016/j.ejso.2013.02.015
The women’s health initiative, a randomised placebo-controlled trial, showed that oestrogen plus progestin increased breast cancer incidence and mortality, which is in contrast to most observational studies. This study compares the trial findings (n=68132) to the observational group (n=93176) of the study. Patients who were ineligible or not interested in the randomised trial were eligible for the observational group. Within this group, patients meeting eligibility criteria of the clinical trial were identified (25328 non-hormone users versus 16121 oestrogen plus progestin users). After a mean follow-up of 11.3 years, 2236 patients with invasive breast cancers were diagnosed. Breast cancer incidence were higher in the oestrogen plus progestin users versus the non-users (HR=1.55; p<0.001). Analyses censoring when a 2-year interval without a mammogram occurred had similar breast cancer association (HR 1.61, p<0.001). Women starting hormone therapy closer to menopause had higher cancer risk with linear diminishing influence as time from menopause increased (p<0.001). Survival after breast cancer was similar between the two groups (HR=1.32, p=0.15).
Journal of the National Cancer Institute 2013; DOI; 10.1093/jnci/djt043
This study compares different methods of analysing sentinel lymph nodes (SLN) between different hospitals. In three hospitals, SLNs were examined with H&E at three levels of paraffin block (n=455). In the fourth hospital (n=86), SLNs were examined with H&E at 10 levels at least. Immunohistochemistry was used in all 4 centres when H&E examinations were negative. Patients in the fourth hospital had higher diagnosis of isolated tumour cells (34.9% versus 5.3%; p<0.001). In the fourth centre SLN positivity rate was 66%, compared to 29% in the other centres. This resulted in 67% of patients in the fourth hospital undergoing cALND, compared to 31% in the other centres (p<0.0001). The clinico-pathological characteristics were similar between the 4 centres. The 5 year regional recurrence in the aforementioned three centres was 2.6% versus 0% in the fourth centre (p=0.37).
European Journal of Surgical Oncology 2013; DOI; 10.1016/j.ejso.2013.02.013
Study investigated the effect of integrated 2D and 3D mammography in asymptomatic women aged >48 years attending population-based breast-cancer screening. Standard double-reading by breast radiologists determined whether to recall the participant based on positive mammography at either screen read. 7292 women were screened (median age 58 years [IQR 54—63]). The study detected 59 breast cancers(including 52 invasive cancers) in 57 women. Both 2D and integrated 2D and 3D screening detected 39 cancers. Authors detected 20 cancers with integrated 2D and 3D only versus none with 2D screening only (p<0·0001). Cancer detection rates were 5·3 cancers per 1000 screens (95% CI 3·8—7·3) for 2D only, and 8·1 cancers per 1000 screens (6·2—10·4) for integrated 2D and 3D screening. The incremental cancer detection rate attributable to integrated 2D and 3D mammography was 2·7 cancers per 1000 screens (1·7—4·2). 395 screens (5·5%; 95% CI 5·0—6·0) resulted in false positive recalls: 181 at both screen reads, and 141 with 2D only versus 73 with integrated 2D and 3D screening (p<0·0001).
Lancet Oncology, 2013;doi:10.1016/S1470-2045(13)70134-7
This study examines if more extensive methods results in more axilla upstaging in patients with false-negative SLN than in patients with true negative SLN. The study cohort included patients from the Swedish multicentre SLN validation study (n=675), as well as the Swedish multicentre SLN study (n=3535). False negative nodes were defined as a negative SLN followed by a positive completion ALND (cALND) or a negative node in patients without cALND who developed isolated axillary recurrence. For each false-negative case (n=50), two random patients with true negative SLN were chosen as controls (n=107). Serial sectioning was performed at 0.2mm levels until the tissue blocks had been exhausted, and two sections at each level was stained with H&E or for IHC. Clinico-pathological characteristics were compared between the false negative and the true positive cases (n=1204). Serial sectioning revealed isolated tumour cells in 14 patients, micrometastasis in 6 patients, and macrometastasis in one patient. This resulted in SLN metastasis in 18% of the false-negative group, as opposed to 11.2% in the true negative group (p=0.245). The risk of false negative SLN was higher in patients with hormone receptor negative tumours (OR 2.5), multifocal tumours (3.39), or if only one SLN was identified (OR 3.57).
British Journal of Surgery, 2013; DOI; 10.1002/bjs.9085
This study compares exemestane (n=3789) to anastrozole (n=3787) in the adjuvant setting for treatment of hormone-dependent early breast cancer in post-menopausal women. Maximum duration of therapy was 5 years or until unacceptable toxicity developed. Hazard ratio of 0.8 was maintained between exemestane and anastrozole. At a median follow-up of 4.1 years, 693 event-free survival (EFS) occurred; 350 for exemestane (9.2%) versus 343 for anastrozole (9.1%). There was no difference in the EFS rate between the two drugs when the nodal status was examined. This was again the case when administration of chemotherapy was examined. Overall, patients with the following factors had better prognosis; bilateral oophorectomy, age 45-59 years, <12 months after hysterectomy, performance status of 0, ER and PR positive receptor tumours, prior radiotherapy, and adjuvant chemotherapy. There was no difference in the overall survival and discontinuation rate was 33.8% for exemestane versus 29.4% for anastrozole. Osteoporosis, hypercholesterolaemia, and abnormal postmenopausal bleeding were less frequent in patients taking exemestane. However, mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent in patients taking anastrozole.
Journal of Clinical Oncology 2013; DOI; 10.1200/JCO.2012.44.7805
This study reviews a single centre experience following 340 nipple-sparing mastectomies (NSMs). Risk reduction was the indication for surgery in 59% with 50 patients (21.6%) testing positive for a BRCA1/2 gene mutation. There were two flap losses and 14 hematomas. Complete nipple necrosis occurred in three cases (0.8%) and partial loss in six patients. Recommendations are made to reduce the risk of nipple necrosis included the following: (a) preserving major perforating vessels (b) elevating skin flaps in the plane between the subcutaneous fat and the breast glandular tissue (c) the use of incisions that do not devascularize the nipple-areola complex.
The Breast Journal 2013; DOI: 10.1111/tbj.12078
Poly Implant Prosthese (PIP) breast implants have been withdrawn due to the use of sub-medical grade materials. This study examines the mechanical properties of PIP implants against medical-grade breast implants. Explanted PIP implants were separated into intact or ruptured groups. Tensile strength, tear resistance, and elongation at break were assessed. Explantation of 18 PIP implants was performed in 10 patients (median 126 months), and 4 implants were removed as controls. Tensile strength, maximal strain at rupture, and tear strengths correlated negatively with implantation times. Statistically significant difference was seen for tensile strength, maximal strain, and tear strength between the intact and ruptured PIP, compared to the controls.
British Journal of Surgery 2013; DOI; 10.1002/bjs.9094
The authors used a sonication method to detach the bacterial biofilm to determine if there was a causal link between bacterial biofilm and capsular contracture following breast implant surgery. The resulting sonication fluid was incubated for 10 days. Appropriate negative controls included sterilised breast implants. 121 implants were analysed from 84 patients. For permanent implants, the median indwelling time was 4 years, compared to 3 months for temporary devices. 98 permanent implant procedures were performed, and 9/98 were excluded due to clinical infection. Sonication cultures grew micro-organisms in 46.4%. Positive sonication culture correlated with the degree of capsular contracture. The most commonly isolated organisms were Propionibacterium acnes and coagulase-negative staphylococci.
British Journal of Surgery 2013; DOI; 10.1002/bjs.9084
‘Best practice diagnostic guidelines for patients presenting with breast symptoms’ by a working group recommended that the routine use of mammogram for symptomatic patients should only be performed in patients aged 40 years and over. Previously mammograms were routinely performed in patients aged 35 years old and over. Retrospective analysis was performed to examine if any cancer cases would have been missed if USS alone was used. Databases were used to identify patients (n=33) diagnosed with breast cancer between the age of 35 and 39 years old. 28/33 patients had been diagnosed with invasive ductal carcinoma. 29/33 patients presented with a breast lump, where 24/33 had clinical grading of P3 or greater. Mammographic grading of M3 or greater was noted in 26/33 patients, whereas USS grading of U3 or greater was noted in 31/33 patients. The tumour size ranged from 10 to 25mm. Sensitivity for detecting malignancy was 72.7% (clinical examination), 78.8% (mammography), and 93.9% (USS) respectively. When clinical examination findings were benign, the sensitivity of detecting malignancy was 55.5% (mammography) and 88.9% (USS) respectively. No cancers would have been missed using the new guideline.
The Breast Journal 2013; DOI; 10.1111/tbj.12074
The management of metastatic breast cancer requires monitoring of the tumor burden to determine the response to treatment. The authors compared the radiographic imaging of tumors with the assay of circulating tumor DNA, CA 15-3, and circulating tumor cells in 30 women with metastatic breast cancer who were receiving systemic therapy. The investigators used targeted or whole-genome sequencing to identify somatic genomic alterations and designed personalized assays to quantify circulating tumor DNA in serially collected plasma specimens. Circulating tumor DNA was successfully detected in 29 of the 30 women in whom somatic genomic alterations were identified; CA 15-3 and circulating tumor cells were detected in 21 of 27 women (78%) and 26 of 30 women (87%), respectively. Circulating tumor DNA levels showed a greater dynamic range, and greater correlation with changes in tumor burden, than did CA 15-3 or circulating tumor cells. Among the measures tested, circulating tumor DNA provided the earliest measure of treatment response in 10 of 19 women (53%).
New England Journal of Medicine, 2013;DOI:10.1056/NEJMoa1213261
The authors conducted a population-based case–control study of major coronary events (i.e., myocardial infarction, coronary revascularization, or death from ischemic heart disease) in 2168 women who underwent radiotherapy for breast cancer between 1958 and 2001 in Sweden and Denmark. The study included 963 women with major coronary events and 1205 controls. The overall average of the mean doses to the whole heart was 4.9 Gy. Rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per gray with no apparent threshold. The increase started within the first 5 years after radiotherapy and continued into the third decade after radiotherapy. The proportional increase in the rate of major coronary events per gray was similar in women with and women without cardiac risk factors at the time of radiotherapy.
New England Journal of Medicine 2013; DOI; 10.1056/NEJMoa1209825
The authors assessed the incidence of unilateral arm lymphoedema after breast cancer and explored the evidence available for lymphoedema risk factors. 72 studies met the inclusion criteria for the assessment of lymphoedema incidence, giving a pooled estimate of 16·6%. The estimate was 21·4% when restricted to data from prospective cohort studies (30 studies). The incidence of arm lymphoedema seemed to increase up to 2 years after diagnosis or surgery of breast cancer and was highest when assessed by more than one diagnostic method, and was about four times higher in women who had an axillary-lymph-node dissection than it was in those who had sentinel-node biopsy. 29 studies met the inclusion criteria for the assessment of risk factors. Risk factors that had a strong level of evidence were extensive surgery and being overweight or obese.
The Lancet Oncology 2013; DOI: 10.1016/S1470-2045(13)70076-7
In this study the authors aim to determine whether bacterial colonization of drains can be reduced by local antiseptic interventions. Standard drain care comprised twice daily cleansing with alcohol swabs. Antisepsis drain care included (1) a chlorhexidine disc at the drain exit site and (2) irrigation of the drain bulb twice daily with dilute sodium hypochlorite (Dakin's) solution. Overall, 100 mastectomy patients with 125 drains completed the study with 48 patients (58 drains) in the control group and 52 patients (67 drains) in the antisepsis group. Cultures of drain bulb fluid at 1 week were positive in 66% of control drains compared with 21% of antisepsis drains. Drain tubing cultures demonstrated more than 50 colony-forming units in 19% of control drains versus 0% of treated drains. Surgical site infection was diagnosed in 5 patients in the control group and 1 patient in the antisepsis group; this was borderline significant.
Annals of surgery, 2013;DOI:10.1097/SLA.0b013e31828c0b85
This study reports subsequent ipsilateral breast events (IBE) in patients with borderline lesions compared with those with DCIS. A total of 143 borderline-lesion patients and 2,328 DCIS patients were identified with a median follow-up was 2.9 and 4.4 years, respectively. 7 borderline-lesion and 172 DCIS patients experienced an IBE. 5 year IBE rates were 7.7 % for borderline lesions and 7.2 % for DCIS. 5 year invasive IBE rates were 6.5 % and 2.8 %, respectively. Similarly, when analyses were restricted to patients who did not receive radiotherapy, or endocrine therapy, or both, borderline-lesion and DCIS patients did not demonstrate statistically significant differences in rates of IBE or invasive IBE.
Annals of Surgical Oncology, 2013;DOI:10.1245/s10434-008-9952-8
Authors conducted a retrospective study to evaluate the local recurrence (LR) rate depending on the use of neoadjuvant chemotherapy (NCT) in breast-conserving surgery (BCS). 166 patients underwent BCS or mastectomy after NCT (NCT group) and 193 patients underwent surgery first (surgery group) in clinical stage III breast cancer patients. In patients whose tumor size was ≤4 cm after NCT, 57 patients underwent mastectomy (mastectomy group), 39 patients underwent preplanned BCS (preplanned BCS group), and 33 patients underwent downstaged BCS (downstaged BCS group). The 5-year LR-free survival rates were 93.6 % in the NCT group and 95.9 % in the surgery group. In the NCT group, the 5-year LR-free survival rates were 96.3 % in the mastectomy group, 94.7 % in the preplanned BCS group and 90.9 % in the downstaged BCS group. High expression of Ki-67 was a predictor of LR in patients in three groups.
Annals of Surgical Oncology, 2013; DOI: 10.1245/s10434-008-9952-8
This systematic review examines the oncological and cosmetic outcome following oncoplastic breast surgery (OPBS). A total of 12 studies remained to form the basis of the systematic review (n=998 patients treated with OPBS). No RCTs were identified, and all the trials were single-centre studies. The mean tumour size ranged from 22 to 34 mm with up to 74 months follow-up. The most commonly used technique involved volume displacement, especially reduction mammoplasties and glandular rotation. OPBS resulted in tumour-free margins in 78-93% of cases. Close margins were seen in 3-13%, and positive margins were seen 0-10%, resulting in completion mastectomy rate of 3-16%. The local recurrence rate varied from 0-7%. 3/12 studies reported operative time, where OPBS required twice the operative time than standard BCS. Complication rate of 20% was the most commonly reported in the 7 studies that reported it.
Annals of surgery 2013; DOI; 10.1097/SLA.0b013e3182888782
This systematic review examined positive margin rates, re-excision rates, and complications from radioactive seed localisation (RSL); an alternative technique to localise non-palpable tumours. 13 potential studies were examined, and 6 were selected for the final analysis, where 2/6 studies were RCTs. Overall, 1611 patients underwent RSL, and mean time to operation ranged from 0 to 4 days from the seed placement. This allows potential flexibility in theatre scheduling. The negative margin rates were 96.7% in the studies from 2010 to 2011. 3/6 studies reported outcome in greater than 300 patients, where negative margin rate varied from 89.5% to 96.7%. Reoperation rate ranged from 4.6% to 27%. Failure of seed placement occurrence was 0% to 7.2%.
British Journal of Surgery 2013; DOI; 10.1002/bjs.9068
The IBCSG trial 23—01 determined whether no axillary dissection was non-inferior to axillary dissection in patients with one or more micrometastatic (≤2 mm) sentinel nodes and tumour of <5 cm. Non-inferiority was defined as a hazard ratio (HR) of less than 1·25 for no axillary dissection versus axillary dissection. 464 patients were in the axillary dissection group and 467 patients were in the no axillary dissection group. 69 disease-free survival events in the axillary dissection group and 55 events in the no axillary dissection group were recorded. Breast-cancer-related events were recorded in 48 patients in the axillary dissection group and 47 in the no axillary dissection group (ten local recurrences in the axillary dissection group and eight in the no axillary dissection group; three and nine contralateral breast cancers; one and nine regional recurrences; and 34 and 25 distant relapses). 5-year disease-free survival was similar between the groups. Patients with reported long-term surgical events (grade 3—4) were all in the group that underwent axillary dissection except one grade 3 motor neuropathy in the group without axillary dissection. One serious adverse event was reported, a postoperative infection in the axilla in the group with axillary dissection.
This study aimed to examine the risk factors for flap necrosis for wise-pattern skin-sparing mastectomy (WPM) in
75 cases. Mean age of the cohort was 48.8 years old, and mean BMI was 24.4. Mean operative time was 158.8 minutes, including contralateral symmetrisation surgeries (n=49). 7 SLNB were performed, and 22 required ALND. Patient outcome was grouped into; healed uneventfully, partial thickness, and full thickness necrosis. Patient risk factors considered were; age, BMI, neoadjuvant chemotherapy (NAC), and smoking status. There were 26 IDC, 31 ILC, 10 DCIS, and 8 prophylactic cases. 9/22 underwent ALND chemotherapy and radiotherapy. Skin flap ischaemic complications were seen in 20/75 breasts (26.6%). All occurred at the ‘T’ junction and along the vertical limb of the wise pattern. Partial thickness necrosis occurred in 11 breasts (14.6%) versus full thickness necrosis in 9 breasts (12%). The former were treated conservatively, whilst the latter required further skin grafts. Implant loss occurred in 4% of breasts. Univariate analysis showed that NAC, smoking, mastectomy specimen weight >681g, and prosthesis weight >468g were significant factors for skin flap necrosis. Logistic regression analysis showed that smoking and weight of prosthesis were independent predictors.
Annals of Surgical Oncology 2013; DOI; 10.1245/s10434-012-2672-0
The authors assessed the frequency and course of CNS relapses, either as first event or at any time in patients with HER2-positive early breast cancer who had been randomly assigned to receive 1 year of trastuzumab or to observation in the HERA trial after a median follow-up of 4 years. Of 3401 patients who had been assigned to receive 1 year of trastuzumab or to observation, 69 (2%) had a CNS relapse as first disease free survival (DFS) event and 22% had a first DFS event not in the CNS. The frequency of CNS relapses as first DFS event did not differ between the group given 1 year of trastuzumab and the observation group. Most CNS relapses were symptomatic.
This study compares the outcome between muscle sparing latissimus dorsi flap (MSLD; n=36) versus extended latissimus dorsi flap (ELD; n=37). All operations were performed consecutively, with ELD being performed between 2007 to 2009, and MSLD between 2009 to 2011. For MSLD, 14 reconstructions were performed as MSLD alone, 18 reconstructions with MSLD with implants, and 4 reconstructions with MSLD with fat grafts (average volume of 64cc). Both groups were well matched in terms of tumour characteristics, adjuvant treatments, and risk factors. The mean age was 42 years old in the MSLD group versus 39.2 years old in the ELD group. The mean BMI was 21.95 in the MSLD group versus 22.18 in the ELD group. Donor site seroma occurred in 5.6% for the MSLD group versus 62.2% in the ELD group (p=0.0001). After 6 months of physiotherapy, limitation in shoulder movement was seen in 0% in the MSLD group versus 8.1% in the ELD group (p=0.081). No flap loss or haematoma was seen in either group. Delayed wound healing was seen in 4.1% in the MSLD group versus 21.6% in the ELD group (p=0.11).
Journal of Plastic, Reconstructive & Aesthetic Surgery; DOI; 10.1016/j.bjps.2013.01.026
This study examines outcome of immediate breast reconstruction (IBR) using Strattice, a porcine-derived acellular dermal matrix (ADM). This included patients who underwent single-stage implant reconstruction, and those who underwent two-stage tissue expander reconstruction. In most cases 8cm x16cm sheet of Strattice was used. The drains were left in place on average of 7 days. Prophylactic intravenous antibiotics were used for 48 hours peri-operatively. 54 patients underwent Strattice reconstruction in 105 breasts, of which 77.1% were prophylactic mastectomies (64.8% were bilateral cases). 96.2% underwent single stage IBR, and the mean implant size was 444.1cc. 9.3% of the cohort were smokers, and 5.7% received radiation. Patients were followed-up for a mean of 41.3 months. Implant loss or explantation occurred in 3.8%. Skin necrosis occurred in 2.9%, and seroma in 1.9%. No significant difference was observed between the oncological and the prophylactic cases in terms of complication rates.
Journal of Plastic, Reconstructive & Aesthetic Surgery; DOI; 10.1016/j.bjps.2012.10.015
Decision-making in breast reconstruction is complicated as women are offered an increasingly large range of options. Alloplastic surgery continues to evolve with the introduction of new prostheses to the breast reconstruction market but with limited patient-reported outcomes data. Evaluating the outcomes of surgical interventions and their impact on patients is imperative to improve the patient decision-making process and to improve quality of care. The authors evaluated the effect of the two most commonly used silicone prostheses on patient-reported satisfaction and health-related quality of life following alloplastic breast reconstruction. Patients were deemed eligible if they had completed alloplastic reconstruction at least 1 year before study initiation. Patients were contacted by mail with the BREAST-Q questionnaire, a contact letter, and an incentive gift card. BREAST-Q scores were compared between shaped cohesive and round cohesive silicone gel implant recipients. Sixty-five round, cohesive, non–form-stable and 63 shaped, cohesive, form-stable silicone gel implant recipients responded, for an overall response rate of 75 percent. BREAST-Q responses showed no difference on any scale, including overall satisfaction with breast and outcome. Item-wise analysis revealed that implant recipients find shaped cohesive form-stable implants to be significantly firmer than cohesive round implants. No difference was found in implant rippling.
Plastic and Reconstructive Surgery, March 2013; doi: 10.1097/PRS.0b013e31827c6d55
In United Kingdom, 20% of women with screen-detected breast cancer undergo a repeat breast operation to achieve clear resection margins. This study aims to evaluate potential predictive factors for repeat operation in patient with screen-detected breast cancer (n=1593). 74% were diagnosed with invasive cancer as opposed to 26% with DCIS. 1315 patients underwent wide local excision with a re-excision rate of 30% (n=396). Of note 133/396 required a mastectomy as the 2nd operation (34%). 28/396 patients required a 3rd operation, and mastectomy rate was even higher occurring in 22/28 cases (79%). Multivariate analysis showed that lobular carcinoma, calcification on mammogram, medullary and tubular carcinomas, and core tumour grade 2 were independent significant predictors for re-operation. Women presenting with microcalcifications had the highest odd ratio of 4.04 (p<0.001) for re-operation. For DCIS, women with tumours>30mm were 3.4 times more likely to undergo re-operation.
The Breast 2013; DOI; 10.1016/j.breast.2012.06.011
This study evaluates the accuracy of axilla ultrasound (USS) combined with needle core biopsy (NCB). Core biopsy was performed for patients who had diffuse or focal eccentric cortical enlargement >3mm, loss of lymph node fatty hilum, and short: long axis size ratio >50%. Biopsy was performed with a 14G needle. Sensitivity and specificity (n=142; December 2008 to May 2009) was carried out against the gold standard of post operative histology. Median patient age was 65 years old. 36% of the cancers were screen detected. Axilla was deemed abnormal on USS in 36% (n=51). In total, 46/51 patients (90%) underwent NCB of axillary lymph nodes: 24/46 (52%) were diagnosed with malignant nodes, 19/46 (41%) had normal nodes, and in 3 cases (7%) no nodal tissue was retrieved. 5/51 with abnormal radiological finding did not undergo NCB since the nodes were in close proximity to the axillary vessels. In total, 52/142 patients (37%) were diagnosed with axillary metastasis at surgery. This resulted in sensitivity of 75% and specificity of 100% for the NCB in predicting axillary metastasis. Invasive ductal carcinoma consisted of 76%, and invasive lobular carcinoma in 16%, and other types in 7%. Patients with lobular carcinomas were consistently under-staged using NCB.
The Breast Journal 2013; DOI; 10.1111/tbj.12042
Pure Tubular Carcinoma (PTC) of the breast is a rare histological subtype of invasive breast cancer characterized by a low rate of lymph node involvement. Currently there is no consensus on less surgical axillary node staging according to this histological subtype. Authors performed a retrospective multi-institutional study. Inclusion criteria were PTC, sentinel lymph node detection (SLND) and conservative breast surgery (n=234). The median pathological tumor size was 9.59 (1–22) mm. SLN were successfully detected in 98% (229/234) of patients. Among the 234 patients, a macrometastasis was found in 6 cases (2.5%), micrometastasis in 15 cases (6.4%), and isolated cells in 2 cases (0.8%). In the case of patients with SLND macrometastasis, half of them had macrometastasis in the complementary axillary lymphadenectomy, and none in the case of SLN only micrometastasis or isolated cells. Of the 122 patients with a pathological tumor size <10 mm, none had sentinel node macrometastasis. According to a multivariate analysis, pathological tumor size (>10 mm) was the only parameter significatively linked to the risk of lymph node involvement.
European Journal of Surgical Oncology; 2013.doi :10.1016/j.ejso.2012.12.009
This study was performed to determine whether c-Kit expression in basal-like breast cancer (BLBC) has any effect on patient outcome. Immunohistochemistry was performed for BLBC (n=149) and for non-BLBC (n=518). The median patient age was 58 years with median follow-up of 39 months. 269 patients underwent mastectomy, and 398 patients underwent breast conserving surgery. Endocrine therapy was administered for 399 patients, chemotherapy to 228 patients, and herceptin to 97 patients. Patients with BLBC had statistically significant poorer disease free survival, larger tumours, and had higher proportion of axillary metastasis. c-kit expression was present in 111 cases (16.6%), and was more prevalent in BLBC (p<0.001), younger patients (p=0.003), and in patients with lymph node metastasis (p=0.014). Moreover, c-kit expression was associated with poor disease free survival (p<0.001) in BLBC. c-kit expression independently predicted for poor disease free survival in BLBC.
British Journal of Surgery 2013; DOI; 10.1002/bjs.9021
Axillary lymph node dissection (ALND) is the removal of level I and II lymph nodes as defined by anatomical landmarks, and various international recommendations state that minimum of 6 or 10 lymph nodes should be removed. In sentinel node biopsies (SNB), blue and or ‘hot’ nodes should be removed. The study was performed to determine the validity of the above stated benchmarks on the minimum number of lymph nodes required. The study cohort consisted of patients with T1 or T2 patients (2004 to 2008; n=71907) who had SNB (45.5%), SNB+ALND (24%), or ALND (30.5%) alone (mean age=59.7 years old). The median numbers of resected lymph nodes were 2 for SNB, 9 for SNB+ALND, and 11 for ALND. Of the patients who underwent ALND alone, 56.7% had >10 lymph nodes resected, compared to 46.2% for the SNB+ALND group. Multivariate analysis showed that >10 lymph nodes were likely to be resected in T2 tumours, younger patients, or had mastectomy. More than 6 lymph nodes were removed in 75.5% of cases for ALND alone versus 67.8% in the SNB+ALND group. For SNB, 83.4% had less than 3 lymph nodes removed. Multivariate analysis showed that this was more likely to be the case in T1 tumours, older patients, or underwent breast conserving surgery.
Annals of Surgical Oncology 2013; DOI; 10.1245/s10434-012-2642-6
This retrospective analysis investigated the association between immediate breast reconstruction (IBR), complications and adjuvant chemotherapy delivery. Comparisons were made between 107 patients who received IBR and 113 who received mastectomy alone. Those receiving IBR were on average younger, with lower body mass index (BMI) and better prognoses. Overall complication rates were comparable (mastectomy alone: 45.1% versus IBR: 35.5%, p = 0.2). There was more return to surgery in the IBR group with 11.5% of tissue expanders requiring removal, whilst more seromas occurred in the mastectomy group. There was no significant difference in the median time to chemotherapy.
The Breast, 2013; doi:10.1016/j.breast.2012.10.008
Fat grafting is widely carried out in breast cancer patients to improve quality in breast reconstruction. This matched-cohort study analysed: (i) 59 intraepithelial neoplasia patients who had undergone lipofilling, with no recurrence between primary surgery and lipofilling and (ii) a control group of 118 matched patients (two controls per lipofilling patient) with the corresponding recurrence-free intervals. Both groups were also matched for main cancer criteria. Median follow-up was 63 and 66 months from surgery and the 5-year cumulative incidence of local event (LE) was 18% and 3% in the lipofilling and control groups respectively. Ki-67 was the significant factor in univariate survival analysis. A subgroup analysis showed that lipofilling increased the risk of LE in women <50 years, with high grade neoplasia, Ki-67 ≥ 14 or who had undergone quadrantectomy.
Annals of Oncology 2013; doi: 10.1093/annonc/mds660
MA17 showed improved outcomes in postmenopausal women given extended letrozole (LET) after completing 5 years of adjuvant tamoxifen. Exploratory subgroup analyses of disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), toxic effects and quality of life (QOL) in MA17 were performed based on menopausal status at breast cancer diagnosis. At diagnosis, 877 women were premenopausal and 4289 were postmenopausal. Extended LET was significantly better than placebo (PLAC) in DFS for premenopausal and postmenopausal women, with greater DFS benefit in those premenopausal. In adjusted post-unblinding analysis, those who switched from PLAC to LET improved DDFS in premenopausal and postmenopausal women.
Annals of Oncology 2013; doi: 10.1093/annonc/mds330
Breast capsular contracture (BCC) is a commonly adverse event post-mammoplastly characterized by an immune response mediated by cytokines. Presence of TGF-β1 polymorphisms has been associated as a risk factor to develop fibroproliferative diseases. This open, controlled, prospective, and pilot clinical trial evaluated the efficacy of Pirfenidone (PFD) in the treatment of BCC (Baker Score III/IV) post-mammoplasty. Twenty BCC cases received PFD and 14 BCC control cases underwent capsulectomy after 6 months of enrollment. Both groups were followed up for 6-12 months to determine the relapse in the absence of PFD. Determination of TGF-β1 polymorphisms was performed to establish a correlation with capsular contracture. PFD group experienced BCC-reduction in all breasts 6 months after enrollment. Only 1 of 20 cases relapsed after follow-up. In capsulectomy group, 2 of 14 cases presented progression to grade IV during presurgical period. All capsulectomy cases relapsed at end of follow-up. Nearly hundred percent of all patients studied in this protocol had a profibrogenic homozygous TGF-β1 polymorphism.
Annals of Plastic Surgery 2013; doi: 10.1097/SAP.0b013e31822284f4
This study describes the operating process and to reports the results of 118 stereotactic vacuum-assisted biopsies performed on a digital breast 3D-tomosynthesis system. A total of 106 patients had a lesion, six had two lesions. Sixty-one lesions were clusters of micro-calcifications, 54 were masses and three were architectural distortions. Patients were in lateral decubitus position to allow shortest skin-target approach (or sitting). Specific compression paddle, adapted on the system, performed, and graduated, allowing localization in X-Y. Tomosynthesis views define the depth of lesion. Graduated Coaxial localization kit determines the beginning of the biopsy window. Biopsies were performed with an ATEC-Suros, 9 Gauge handpiece. All biopsies, except one, have reached the lesions. Five hemorrhages were incurred in the process, but no interruption was needed. Eight breast hematomas, were all spontaneously resolved. One was an infection. About 40% of patients had a skin ecchymosis. Processing is fast, easy, and requires lower irradiation dose than with classical stereotactic biopsies. Histology analysis reported 45 benign clusters of micro-calcifications, 16 malignant clusters of micro-calcifications, 24 benign masses, and 33 malignant masses. Of 13 malignant lesions, digital 2D-mammography failed to detect eight lesions and underestimated the classification of five lesions. Digital breast 3D-tomosynthesis depicts malignant lesions not visualized on digital 2D-mammography.
The breast journal 2013; DOI: 10.1111/tbj.12044
This study analyzes clinical implications of the thoracodorsal nerve division in the latissimus dorsi musculocutaneous flap breast reconstruction. Prospective cohort study was conducted on 29 patients. Breast reconstruction with latissimus dorsi musculocutaneous flap was performed unilaterally in 20 patients or bilaterally in 9 women (38 breasts). Thoracodorsal nerve was divided during reconstruction of 20 breasts (group 1) and was preserved for 18 breasts (group 2). There were no differences in decrease in volume between groups 1 and 2. Respondents in group 1 in comparison to group 2 showed similar satisfaction of the tissue consistency of the reconstructed breast and the level of symmetry between both breasts, gave lower scores for painfulness, animation and higher scores for the overall satisfaction about the reconstructed breast.
The breast 2013; doi:10.1016/j.breast.2013.01.001
Authors evaluated the long-term results and patient’s satisfaction in reduction mammaplasties for symptomatic mammary hypertrophy (n=92). 90.5% of all patients stated, that they would retrospectively re-opt for a reduction mammaplasty. Preoperative patients' age, BMI and severity of macromasty-related symptoms were found to be factors positively correlated with a high post-interventional satisfaction with the achieved symptom-relief and the overall outcome. No correlation was found between the amount of intra-operatively resected breast tissue and the post-operative patients’ assessment. Patients’ assessment regarding the achieved post-operative symptom relief was comparable for all three surgical techniques, however the overall outcome rating for both bi-pedicled approaches (Stroembeck and Ribeiro) was higher compared to the mono-pedicled Bostwick technique.
Archives of Gynaecology and Obstetrics 2013; DOI: 10.1007/s00404-012-2620-z
The authors describe their outcome in 55 breasts of performing two stage implant based reconstruction for nipple-sparing mastectomy (NSM) using a lateral inframammary fold (IMF) incision; an incision which is more aesthetically pleasing. None of the patients were smokers, and none received prior radiotherapy to the breast. All patients were infiltrated with saline solution containing lidocaine and epinephrine, which provided hydrodissection as well as improved haemostasis. Sharp dissection was used with minimal electrocautery. If adequate exposure was possible, the axillary procedures were performed through the same incision. The tissues underlying the nipple areolar complex (NAC) were sent for frozen section before proceeding with reconstruction. Acellular dermal matrix was used with the implant or expander for reconstruction in 62% of the cases. The average patient age was 46 years old, with mean follow-up of 12 months. 12 mastectomies were therapeutic, and the remaining 43 performed for prophylactic reasons. 7/9 patients underwent unilateral sentinel lymph node biopsies through the same incision. Mastectomy flap necrosis occurred in two breasts (4%), partial necrosis of the NAC occurred in 6% and cellulitis in 5%.
The breast journal 2013; DOI: 10.1111/tbj.12043
This study evaluates the extent of local tumour excision and re-operation rates between oncoplastic wide local excision (WLE, n=37) as opposed to standard WLE (n=121). Tumour size was greater for the oncoplastic WLE group compared to the standard WLE group. Margins less than 5mm were found in 28.9% of the standard WLE group, compared to 5.4% in the oncoplastic WLE group. This resulted in the same figures for the re-excision rates. 17/35 who required re-excision of margins underwent mastectomy in the standard WLE group, as opposed to 1/2 in the oncoplastic WLE group. There were no differences in would infection and there were no reported local recurrences with overall follow-up at 5 years.
The breast journal 2013; DOI: 10.1111/tbj.12047
The aim of this retrospective study was to assess the impact of immediate autologous reconstruction on lymphodema occurrence (n=712). The diagnosis of lymphoedema was made using arm volumetry, and the Campisi staging system. In this cohort, T1 stage tumour was seen in 49.6%, T2 stage in 48%, and T3 in 2.4%. No axillary metastasis was seen in 62.9%, as opposed to 37.1% with axillary metastasis. Adjuvant chemotherapy was administered in 82.7%, and radiotherapy in 15.9%. 117/712 underwent autologous immediate breast reconstruction. Lymphoedema was seen in 17% of the patients (n=121). Multivariate logistic regression analysis showed that lymphoedema was associated with delayed breast reconstruction, the number of lymph nodes excised and radiotherapy.
The Breast 2013; DOI: 10.1016/j.breast.2012.04.009
This multicentre randomised control trial investigates the outcome between sentinel node biopsy (SNB) alone versus completion axillary lymph node dissection (ALND) in patients with early stage breast cancer who have SNB-confirmed micrometastasis. Inclusion criteria were patients with tumour size <3.5cm, and clinical N0, M0. Patients were randomised to completion ALND (control; n=112) or clinical follow-up (experimental; n=121). In the control group 13% of completion ALND were positive for metastasis, with 6/15 who had one additional micrometastasis only. No significant difference was detected between the two study arms regarding adjuvant treatment. 3 patients suffered from recurrence in the experimental group (2.5%), compared to 1 patient (1%) in the control group. Global disease free survival (DFS) rate was 98.2%, and no cancer-specific death was observed. Kaplan-Meier analyses showed no statistically significant differences in DFS between the two arms.
Annals of Surgical Oncology 2012; doi; 10.1245/s10434-012-2569-y
This study evaluates the intrinsic subtypes of tumours which have low ER expression (1-10%) and to examine if the current cut-off of 1% positive cells to define ER-positive status reflects the molecular biology and the clinical course. ER, PR, and HER2 status was determined using immunohistochemistry, and ER status was divided into ER- (0%), ER+ (>10%), and low ER staining (1-10%). Gene expression data was analysed for the 26 low-ER-staining tumours, and their intrinsic subtype was determined. Under the ASCO/CAP guidelines, those tumours would be considered ER positive. However, molecular analyses showed that 62% were basal like, and 27% as HER2 enriched, and hence ER-negative subtypes.
Annals of Surgical Oncology 2012; doi; 10.1245/s10434-012-2588-8
This study evaluates locoregional recurrence in patients who underwent breast conserving surgery (BCS) before and after neoadjuvant chemotherapy (NAC). 2331 patients (78%) underwent BCS first, and 652 patients (22%) underwent NAC first. 93% of patients who received NAC had stage II or III disease at presentation, compared to 21% of those who underwent surgery first. After NAC, only 47% of patients had stage II or III disease (p<0.001). The median follow-up for surgery first patient was 7.9 years, with 5- and 10-year local-regional recurrence (LRR)-free survival rates of 97% and 94%. For NAC patients, median follow-up was 7.2 years, with 5- and 10-year LRR-free survival rates of 93% and 90%. When presenting clinical stage was taken into account, there were no differences in LRR-free survival rates between the two groups. 7% of surgery first group suffered from distant metastasis, compared to 16% in the NAC group (p<0.001). Multivariate analyses showed that age<50 years old, clinical stage III, grade 3, ER negative disease, omission of endocrine therapy in ER positive patients, lymphovascular invasion, multifocality, positive margins were associated with LRR. Adjusting for these factors, there were no differences between the two groups.
Annals of Surgery 2012; doi; 10.1097/SLA.0b013e3182805c4a
The authors used Surveillance, Epidemiology, and End Results data to examine trends from 1976 through 2008 in the incidence of early-stage breast cancer (ductal carcinoma in situ and localized disease) and late-stage breast cancer (regional and distant disease) among women 40 years of age or older. The introduction of screening mammography in the United States has been associated with a doubling in the number of cases of early-stage breast cancer that are detected each year. Concomitantly, the rate at which women present with late-stage cancer has decreased by 8%. After excluding the transient excess incidence the authors estimated some tumors were detected on screening that would never have led to clinical symptoms
N Eng J Med 2012; DOI: 10.1056/NEJMoa1206809
The authors investigated the efficacy and safety of adjuvant lapatinib for patients with trastuzumab-naive HER2-positive early-stage breast cancer, started at any time after diagnosis. This study was a placebo-controlled, multicentre, randomised phase 3 trial. Between August, 2006, and May, 2008, 3161 women were enrolled and 3147 were assigned to lapatinib (n=1571) or placebo (n=1576). Median follow-up was nearly 48 months. 210 (13%) disease-free survival events had occurred in the lapatinib group versus 264 (17%) in the placebo group (not significant). Central review of HER2 status showed that only 2490 (79%) of the randomised women were HER2-positive. 13% of HER2-positive patients in the lapatinib group and 17% in the placebo group had a disease-free survival event (borderline significant).
Lancet Oncology, 2013;DOI:10.1016/S1470-2045(12)70508-9
The authors aimed to compare ultrasound-guided surgery with palpation-guided surgery with respect to margin status and extent of healthy breast tissue resection. 134 patients were eligible for random allocation. 3% of 65 patients allocated ultrasound-guided surgery had tumour-involved margins compared with 17% of 69 who were assigned palpation-guided surgery. 11% in the ultrasound-guided surgery group and 28% of the palpation-guided surgery group required additional treatment. Ultrasound-guided surgery also resulted in smaller excision volumes.
Lancet Oncology, 2013;doi:10.1016/S1470-2045(12)70527-2
The aim of the study was to examine if molecular features of breast cancer have an influence on the accuracy of MRI, which is used to monitor response to neoadjuvant chemotherapy (NAC). The cohort included 463 patients treated with NAC from 2006 to 2010. ER positive cases were seen in 52.9%, PR positive in 36.5%, and HER2 positive in 35%. Triple negative cases were seen in 24.6%, luminal A in 40.4%, luminal B in 13.6%, and HER2 subtype in 21.4%. Pathological complete response was seen in 11.4%. The mean size difference between MRI-predicted tumour size and pathological tumour size was 1.39cm. Overall there was good agreement between MRI and pathology. Initial tumour stage, younger age (<45 years old), and ER positive tumours had a significantly higher discrepancy between MRI and pathology. MRI was most accurate for the triple negative patients, but least accurate for luminal A and B patients. In HER2 positive patients, treatment with HER2-targeted agents resulted in less accurate MRI prediction.
Annals of Surgery, 2013;DOI:10.1097/SLA.0b013e3182686bd9
Lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) are risk factors for developing subsequent invasive carcinoma, rather than a direct precursor lesion. The authors identified patients diagnosed with LCIS and ALH only on core biopsies and outcomes in those who underwent surgical excision biopsies was investigated. Out of 285 patients, 201 (71%) patients underwent surgical excision. The indications for the core biopsies were new calcifications (62%), palpable mass (4%), architectural distortion (2%), and new nodule (2%). In 30% the indications were unknown. The mean age of the cohort was 54 years old (range of 36 to 84 years old). Patients with pleomorphic LCIS (pLCIS) and LCIS were most likely to undergo surgical excision (100% and 80% respectively). On core biopsies, ALH was seen in 40%, LCIS in 35%, lobular neoplasia (LN) in 25%, and pLCIS in 1%. On the resection specimens, ALH was seen in 18%, LCIS in 26%, LN in 26%, pLCIS in 1%, no cancer in 15%, DCIS in 3%, IDC in 5%, and ILC in 4%. Of the patients who underwent surgery, 13% (n=26) were upgraded to malignancy (8% of ALH cases and 19% of LCIS cases).
Annals of Surgical Oncology, 2013;DOI:10.1245/s10434-012-2538-5
The aim of this study was to assess the value of computed tomography (CT) staging of the chest, abdomen and pelvis in patients with poor prognostic breast tumours and no symptoms of metastatic disease who had undergone primary surgical management. Sixty-seven patients (80%) in the poor prognostic group underwent a staging CT. Forty-seven patients (70%) had no signs of metastatic disease on the staging CT. Two patients (3%) were diagnosed with metastatic disease, on the basis of the initial CT scan. Eighteen patients (27%) had an indeterminate finding requiring further investigation, generating 21 additional imaging tests – following this only one additional patient was diagnosed with metastatic disease. Seventeen patients with an initially indeterminate finding did not have metastatic disease, giving a false-positive rate of 25%. In total, three patients (4%) had a final diagnosis of metastatic disease.
The Breast, 2012;doi:10.1016/j.breast.2012.08.001
This study was conducted to evaluate cumulative survival and the risk of breast cancer death among Japanese women aged 40–69 years. They divided into patients into three groups: mammography (MMG, n=429) with clinical breast examination (CBE, n=522), CBE alone, and self-detection (n=3447) and matched with screened women. Five-year survival for women in the MMG with CBE, CBE, and self-detection groups was 96.8, 92.7, and 86.6 %, respectively. The hazard ratios for breast cancer death was 2.38 among CBE-screened and 4.44 among self-detected cases for women aged 40–49 years, but was 3.00 among CBE-screened and 4.51 among self-detected cases for women aged 50–69 years relative to cases screened by use of MMG with CBE.
Breast Cancer 2012; doi: 10.1007/s12282-012-0434-2
The authors compared the incidence of breast cancer–related lymphedema following reconstruction versus mastectomy alone. Individuals were cross-matched for age, axillary intervention, and postoperative axillary irradiation. The incidence of lymphedema was based on the presence of arm edema that lasted more than 6 months and was documented clinically. Of the 574 cross-matched patients included in the study, 6.8% developed lymphedema. Patients who did not undergo reconstruction were significantly more likely to develop breast cancer–related lymphedema (9.9% vs. 3.7%). Postoperative axillary radiation therapy, one or more positive lymph nodes, and body mass index of >25 were also associated with an increased incidence of lymphedema. In those reconstruction patients who developed lymphedema, this was significantly later than in nonreconstruction patients.
Plastic and Reconstructive Surgery 2012; doi: 10.1097/PRS.0b013e31826d0faa
Fluorescence imaging (FI) for sentinel node (SN) identification enables real time lymphography, avoids radiation and the time required for the radiotracer to reach the SN. The authors report the use of indocyanine green (ICG) FI with blue dye (n=108), and with blue dye alone (n=393). Both the blue dye and ICG were injected in the subareolar region. All fluorescent and/or blue nodes were excised. The mean number of sentinel node excised was 1.6 in the blue dye alone group, compared to the mean of 2.2 in the ICG-blue dye group. The SN identification rate was 100% in the combined group versus 95.7% in the blue dye alone group (p=0.0037). Both groups were well matched in terms of tumour biological characteristics.
Annals of Surgical Oncology 2012; doi: 10.1245/s10434-012-2478-0
This study evaluates the potential risk factors of locoregional recurrence (LRR) in nipple-sparing mastectomy (NSM) in 948 breasts with of patients with false-negative, frozen-section or close margins of retroareolar specimen. Of 948 NSM procedures, there were 88 false-negative, frozen-sections and 10 close margin cases. The 5-year cumulative incidence of LRR and NAC recurrence was 11.2 % and 2.4 %, respectively. Univariate analysis revealed that nipple-areolar complex (NAC) recurrence in this group was significantly associated with in situ carcinoma, high grade, ER negative status, HER2-overexpression, and close margins. Kaplan-Meier analysis showed that in situ carcinoma as the primary tumour a significant predictor of NAC recurrence.
Annals of Surgical Oncology 2012; doi: 10.1245/s10434-012-2514-0
Despite the increasing use of acellular dermal matrix, its disadvantages include cost and increased rate of complications. The authors report an alternative technique which uses autologous dermal graft from pre-existing abdominal scars to provide lower pole coverage. 16 patients elected to have partial muscle coverage with dermal autograft (n=26, including bilateral cases). The abdominal scar was excised in an elliptical fashion measuring 16 x 6 cm and 26 x 6 cm for unilateral and bilateral cases respectively. The marked skin was de-epithelialized, and the dermis was harvested to cover the lower pole of the expander. There were 11 immediate reconstructions. The mean time of autograft harvest and preparation was 38 +/- 9 minutes. There were no implant loss, but two patients suffered from cellulitis which resolved with oral antibiotics, and one patient had delayed wound healing without expander exposure. 14/16 patients were satisfied with the scar appearance. At expander removal, all autografts had fully incorporated with the remainder of the capsule.
Plastic and Reconstructive Surgery 2012;doi:10.1097/PRS.0b013e31826d0f87
Staging asymptomatic patients with evidence of metastatic disease in the axilla remain controversial with practice varying in different centres. This retrospective study evaluates the role of CT staging in asymptomatic patients with poor prognostic features (NPI>5.4). The cohort included patients with operable breast cancer (January 2008 to December 2009). Patients with DCIS and those treated with neoadjuvant chemotherapy or endocrine therapy were excluded. No bone scintigraphy was performed. In the study period 84 out of 740 patients had an NPI >5.4, of which 67/84 (80%) underwent a staging CT. 47/67 (70%) had no evidence of metastatic disease on the CT scan. 2/67 (3%) were diagnosed with metastatic disease. 18/67 (27%) had indeterminate findings that required further tests (false positive rate of 25%), which revealed one additional patients with metastasis. Therefore, 3/67 (4%) were diagnosed with metastatic disease. The positive predictive value of diagnosing asymptomatic metastasis was 15%.
The Breast 2012; doi: 10.1016/j.breast.2012.08.001
Across 12 sites 72030 screening mammograms and 8647 screening ultrasounds were performed to assess the tumour detection rate in screened women with dense breast tissue. 28812 were diagnosed with high breast density, but only 8647/28812 underwent subsequent ultrasound scan (30%). 86% (7451/8647) were diagnosed with Breast Imaging Reporting and Data System Codes (BIRADS) 1 and 2, 9% (767/8647) were BIRADS 3, and 5% (429/8647) were BIRADS 4 and 5. In the latter group, 28 patients were diagnosed with breast cancer. For screening ultrasound scan, this resulted in positive predictive value of 6.7%, and negative predictive value of 99.9%. Sensitivity was 96.6% and specificity was 94.9%. Screening ultrasound resulted in an additional yield of 3.25 per 1000 cancers in women with dense breasts and normal screening mammograms. The cost per breast cancer found was estimated to be $110241.
The Breast Journal 2012; doi: 10.1111/tbj.12003
Triple-negative breast cancer (TNBC) is characterized by aggressive behavior and poor prognosis. While >50 % of patients with inherited BRCA1 mutations have TNBC, the prevalence of BRCA1 mutations in patients with TNBC remains unclear. Deciphering the relationship between BRCA1 and TNBC is critical to understanding the etiology of TNBC, leading to improved patient counseling and treatment. All female patients with TNBC enrolled in the Clinical Breast Care Project were identified. Genomic DNA was isolated from blood and the exonic regions of the BRCA1 gene were amplified and sequenced. Sequence data was analyzed and mutations identified using Sequencher 4.10.1. Of the 190 women with TNBC, genomic DNA was available for 182. Seventy percent of patients were considered high-risk for having a BRCA1 mutation based on the National Comprehensive Cancer Network criteria. Clinically relevant mutations were detected in 16 (9 %) patients ranging in age from 26 to 69 years at diagnosis. Six of these patients were diagnosed >50 years. The C61G mutation was found in three Caucasian women diagnosed >40 years, while six African-American women had mutations, including the 943ins10 West African founder mutation.
Breast Cancer Research and Treatment, November 2012; 10.1007/s10549-012-2348-2
Authors aim was to compare the ability of radiologists to detect breast cancers using one-view breast tomosynthesis (BT) and two-view digital mammography (DM) in an enriched population of diseased patients and benign and/or healthy patients. All participants gave informed consent. The BT and DM examinations were performed with about the same average glandular dose to the breast. The study population comprised patients with subtle signs of malignancy seen on DM and/or ultrasonography. Ground truth was established by pathology, needle biopsy and/or by 1-year follow-up by mammography, which retrospectively resulted in 89 diseased breasts (1 breast per patient) with 95 malignant lesions and 96 healthy or benign breasts. Two experienced radiologists, who were not participants in the study, determined the locations of the malignant lesions. Five radiologists, experienced in mammography, interpreted the cases independently in a free-response study. The diagnostic accuracy of BT was significantly better than that of DM. The average sensitivity of BT was higher than that of DM (∼90% vs ∼79%0) while the average false-positive fraction was not significantly different.
British Journalof Radiology 2012; doi: 10.1259/bjr/53282892
The authors evaluated long-term outcomes following tissue expander breast reconstruction with and without fat grafting. A retrospective review was performed of consecutive patients undergoing mastectomy with immediate tissue expander reconstruction from April of 1998 to August of 2008. Demographic, operative, oncologic, and postoperative factors were recorded, including the use of fat grafting. A review of 886 patients (n = 1202 breasts) revealed no significant differences in demographics, operative characteristics, tumor staging, or radiation therapy exposure between fat-grafting (n = 90 breasts) and non–fat-grafting (n = 1112 breasts) patients. Ninety-nine fat-grafting procedures were performed an average of 18.3 months after reconstruction, with one complication (fat necrosis). Grafting did not affect local tumor recurrence or survival when compared with non–fat-grafted breasts. Complication following reconstruction, including a poor cosmetic result, was an independent predictor of undergoing subsequent fat grafting.
Plastic & Reconstructive Surgery; November 2012;doi: 10.1097/PRS.0b013e318267d34d
This study aims to evaluate the effect of the two most commonly used silicone prostheses on patient-reported satisfaction and health-related quality of life following alloplastic breast reconstruction. Patients were deemed eligible if they had completed alloplastic reconstruction at least one year prior to study initiation. Patients were contacted by mail: the BREAST-Q(C) questionnaire, a contact letter, and an incentive gift-card were included. BREAST-Q(C) scores were compared between shaped cohesive and round cohesive silicone gel implant recipients. 65 round cohesive non form-stable and 63 shaped cohesive form-stable silicone gel implant recipients responded for an overall response rate of 75%. BREAST-Q(C) responses showed no difference on any scale including overall satisfaction with breast and outcome. Item-wise analysis revealed that implant recipients find shaped cohesive form-stable implants to be significantly firmer than cohesive round implants. No difference was found in implant rippling.
Plastic and Reconstructive Surgery 2012; doi: 10.1097/PRS.0b013e31827c6d55
The aim of this study was to assess local control, morbidity, choice of flap reconstruction, patient selection and overall long-term survival following surgical salvage of patients with chest wall recurrent breast cancer. 40 patients were treated with wide soft-tissue resection and immediate flap reconstruction. Full-thickness chest wall resection was performed in 19 cases including three extended forequarter amputations. Chest wall stabilisation involved a synthetic mesh in 12 patients, fascia lata in two patients, free rib grafts in one patient and synthetic mesh and free rib graft in one patient. Soft-tissue reconstruction consisted of microvascular free flaps in seven patients and pedicled flaps in 33 patients. In-hospital mortality was 0% and 30-day mortality was 5%. There were no flap losses. In patients operated on with curative intent (n = 31) median disease-free interval was 31 months and median survival was 52 months.
Journal of Plastic, Reconstructive and Aesthetic Surgery 2012; doi:10.1016/j.bjps.2012.09.027
The study report a single-centre experience of intraoperative ultrasound-guided (IOUS) excision, combined with intraoperative assessment of macroscopic pathologic and ultrasound margins in non-palpable invasive cancers indicated for conservative breast therapy (n=225). The lesion was located in the operating room with a high-frequency ultrasound probe, which was then used to guide surgical removal. The sensitivity of IOUS localization was 99.6% (224/225 cases). Only one cancer of less than 5 mm was not localized. A second operation was required to remove margins in the 4% of cases (9/225). In 5 cases remains of in situ or invasive carcinoma were found. In two cases, conservative surgery was converted to mastectomy.
The Breast, November 2012;doi:10.1016/j.breast.2012.10.006
This study evaluates whether omission of axillary dissection altered decision for adjuvant chemotherapy (ACT) in patients who underwent breast conserving surgery (BCS) with one or two positive sentinel lymph nodes (SLN). Each case was anonymised and discussed at MDT meeting in two rounds. Information regarding age, histopathology, tumour biomarkers, and number of resected and positive SLNs (micro- and/or macrometastasis) were available in the first round. In the second round, information regarding total number of positive and resected lymph nodes was added from the axillary dissection. Two medical oncologists chose between no ACT, discuss ACT, and recommend ACT. The outcome of each round was compared as to what ACT decisions were undertaken. Total cohort size of this retrospective study was 321, with 77% who received ACT. All patients underwent whole breast radiotherapy. The median number of positive lymph node was 1 (macrometastasis in 55%), and in 70% no additional metastasis was found in the non-SLNs. Multivariate analysis showed that macrometastasis, lymphovascular invasion, and hormone receptor positivity were independent predictors of non-SLN involvement. At round 1; ACT was recommended for 52%, to be discussed for 23%, and not recommended for 25%. At round 2; ACT was recommended for 62%, to be discussed for 16%, and not recommended for 22%. Most of the changes occurred in patients with luminal A and B/HER2 negative subset. An exploratory analysis in patients in this subset showed that high Ki67 level was the only independent predictor of a no change in the indication for ACT.
Annals of Surgical Oncology 2012; DOI; 10.1245/s10434-012-2505-1
The aim of the study was to examine pathological response rates in patients treated with neo-adjuvant chemotherapy (NAC) for invasive lobular carcinoma (ILC). A total of 30 patients were available for analysis with the median age of 50 years old. All presented with stage II or III disease, and were hormone receptor positive (median follow-up 29.5 months). 53.3% of the cohort received NAC regimen of anthracycline and taxanes. Histological subtypes consisted of classical-type (53.3%), pleomorphic (23.3%), and mixed (16.7%). Majority required a mastectomy operation (83.3%). Four out five patients who underwent breast conserving surgery subsequently required mastectomy also. 36.7% had residual cancer burden (RCB) II disease, and 60% had RCB III disease. One patient (3.3%) had RCB I disease. There was no loco-regional recurrence during the follow-up period. Four patients (13.3%) developed distant metastasis, of which all had RCB III disease.
The Breast Journal, 2012:DOI;10.1111/tbj.12006
This single-arm phase 2, open-label, multicentre study aimed to investigate the combination of lapatinib plus capecitabine for the treatment of previously untreated brain metastases from HER2-positive breast cancer. The study enrolled 45 patients, 44 (98%) of whom were assessable for efficacy, with a median follow-up of 21·2 months (range 2·2—27·6). 29 patients had an objective CNS response; all were partial responses. Of all 45 treated patients, 22 (49%) had grade 3 or grade 4 treatment-related adverse events, of which the most common were diarrhoea in nine (20%) patients and hand-foot syndrome in nine (20%) patients. 14 (31%) patients had at least one severe adverse event; treatment was discontinued because of toxicity in four patients. No toxic deaths occurred.
Lancet Oncology, 2012; doi:10.1016/S1470-2045(12)70432-1
This retrospective study investigates the outcomes in of patients with positive lymph nodes treated with either mastectomy and sentinel node biopsies (SNB) (n=210) versus breast conserving surgery (BCS) with or without radiotherapy (n=325). The patients in the mastectomy group had larger tumours compared to the BCS group (median 1.5 cm vs 1.2 cm). In both groups, a median of three lymph nodes were dissected, of which one contained cancer. Sentinel node involvements were in majority N0 or N1, with no differences between the two groups. Significantly greater proportion of patients in the mastectomy group received chemotherapy compared to the BCS group (68% vs 56%). 94% of the BCS group received radiotherapy as opposed to 5% in the mastectomy group. There was no difference in the endocrine treatment between the two groups. There was no difference in the locoregional failure rate between the two groups. Disease free and overall survival were lower in the BCS group.
Annals of Surgical Oncology 2012; DOI; 10.1245/s10434-012-2386-3
This study reports outcomes on patients who received second breast conserving surgery (BCS)
after developing ipsilateral tumour recurrence following original BCS and radiotherapy (n=161). The median follow-up was 81 months. Median age for ipsilateral tumour recurrence was 53 years. 20.5%
received chemotherapy and endocrine treatment, 23% endocrine treatment only, 24.8% chemotherapy only, and 31.7% received no systemic therapy. 5-year overall survival was 84%. Cumulative 5-year
incidence of a second local event was 29%. Multivariate analyses showed that ipsilateral tumour recurrence size greater than 2cm and relapse before 48 months were associated with the risk of a second
local event (Hazard ratio of 3.3 and 1.9 respectively). These findings were significant after adjusting for the effect of adjuvant treatment. Patients with ipsilateral tumour recurrence less than 2cm
and relapse after 48 months had 5-year relapse rate of 15.2%. This increased to 31.2% when the relapse occurred before 48 months, and was even higher at 71.2% when the ipsilateral tumour recurrence
size was greater than 2cm.
Annals of Surgical Oncology 2012; DOI; 10.1245/s10434-012-2404-5
This study assesses the safety of perioperative use of low-molecular-weight heparin (LMWH) in the setting of breast reduction surgery. Retrospective assessment of the reoperation rate due to haematoma formation for breast reductions performed under a regimen of preoperative and postoperative administration of LMWH during a 10-year period. A total of 720 patients (1358 breasts) received preoperative and postoperative treatment with LMWH. Reoperation due to haematoma formation was required for 37 breasts in 37 patients (5.1% of patients and 2.7% of breasts). Eight patients (1.1%) required transfusion. No patient or operative factors were associated with the need for reoperation. There were no documented cases of deep vein thrombosis or VTE.
Journal of Plastic, Reconstructive and Aesthetic Surgeons 2012; doi:10.1016/j.bjps.2012.05.027
This economic evaluation compared genomic test–directed chemotherapy using the Oncotype DX 21-gene assay with chemotherapy for all eligible patients with lymph node–positive, estrogen receptor–positive early-stage breast cancer.
Authors performed a cost–utility analysis using a state transition model to calculate expected costs and benefits over the lifetime of a cohort of women with estrogen receptor–positive lymph node–positive breast cancer from a UK perspective. The incremental cost-effectiveness ratio for Oncotype DX–directed chemotherapy using a recurrence score cut off of 18 was £5529 per QALY. The probability that test-directed chemotherapy is cost-effective was 0.61 at a willingness-to-pay threshold of £30 000 per QALY. Results were sensitive to the recurrence rate, long-term anthracycline-related cardiac toxicity, quality of life, test cost, and the time horizon.
J National Cancer Institute. 2012. doi: 10.1093/jnci/djr484
The purpose of this study was to determine the accuracy and value of breast ultrasound for primary imaging evaluation of women 30-39 years of age who present with focal breast signs or symptoms. There were 1208 cases in 954 patients. Outcomes were benign in 98.1% and malignant in 1.9% cases. Sensitivities for ultrasound and mammography were 95.7% and 60.9%, respectively. Specificities for ultrasound and mammography were 89.2% and 94.4%, respectively.. Mammography detected one additional malignancy in an asymptomatic area in a 32-year-old woman who was subsequently found to have a BRCA2 gene mutation.
American Journal of Roentegenology;2012. doi: 10.2214/AJR.12.8842
The authors tested the hypothesized that, for obese patients, delayed abdominal-based free flap (rather than implant-based and immediate) breast reconstruction would result in fewer overall complications and reconstruction losses. The analysis included 990 breast reconstructions (548 flaps versus 442 implants) in 700 patients. Age, smoking, medical illness, and body mass index>37 predicted overall complications on regression analysis. Implants demonstrated a higher failure rate (15.8 percent) than flaps (1.5 percent). Among the obese there was a trend toward more implant failures in immediate rather than delayed reconstructions (16.8 versus 5.3 percent). Differences between immediate implant versus flap reconstruction failure rates were highest among more obese patients.
Plastic and Reconstructive Surgery 2012:doi: 10.1097/PRS.0b013e318267efc5
By correlating clinical outcome with CT angiography findings, a formula for predicting risk of skin or fat necrosis has been developed termed flap viability index (FVI). The aim of the study was to develop a tool which predicts risk of partial flap necrosis and maximum survival flap weight based on the number of perforator arteries, their site and diameter. Perforator position was marked in relation to the umbilicus and 50 DIEP flaps (mean weight= 0.62 Kg) in 45 patients were analysed. The harvested flap was weighed after the excess tissue was trimmed. Flaps were monitored up to 6 weeks post-surgery. Fat necrosis was determined by clinical examination with aid of ultrasound scan. Skin necrosis of more than 5 x 15 mm was debrided within 10 days of surgery. 7/50 (14%) flaps sustained skin or fat necrosis during the follow-up. When the necrosis and no necrosis groups were compared, there was no difference in perforator numbers (p=0.45), and in mean vertical dimensions of perforator position (p=0.26). Perforators closer to midline in horizontal dimension had less likelihood of necrosis (p=0.048). Similar outcome was seen in flaps with larger perforators (higher FVI) with p value of 0.037. All patients with FVI of less than 10 suffered from skin or fat necrosis. In patients with FVI>20, no skin or fat necrosis was seen.
2012, DOI: 10.1016/j.bjps.2012.05.015
This study examines the role of radiotherapy in acellular dermis assisted implant reconstruction versus traditional submuscular implant reconstruction. The study cohort included 417 breasts (592 breasts) from 2006 to 2008. Two types of acellular dermis was used; Alloderm and flexHD. Mean follow-up for acellular dermis group (n=199) was 23.2 months versus 24.4 months in the non-acellular dermis group. All patients underwent expander reconstruction initially. After expansion, selected patients underwent radiotherapy. Following this, permanent implant was inserted. Primary outcome examined was complication rates; infection, explantation, haematoma, seroma, pain, and flap necrosis.Acellular dermis group were more overweight (p=0.0001), and had larger expanders inserted (p=0.0003). Time to exchange to permanent implant was 6 months for non-radiated group, compared to 11.8 months for radiated group. There were no difference in complication rates between acellular dermis group and non-acellular group; overall complication (p=0.19), explantation (p=0.63), infection (p=0.17), seroma (p=0.18), pain (p=0.6). However, age>50 years old, BMI>30, and smoking were significant risk factors for explantation, and overall complication rate.
In subgroup analysis of the non-acellular group, those who received radiotherapy had significantly higher rate of total complication (p=0.003), pain (p<0.0005), and explantations (p=0.04). This is in contrast to the acellular group, where radiotherapy did not result in increase in total complication (p=0.14), pain (p=0.1), and explantations (p=0.14).
Plastic & Reconstructive Surgery 2012, DOI: 10.1097/PRS.0b013e318262f009
Occult breast cancer presents with axillary metastasis without detectable primary breast tumour. They present diagnostic and therapeutic challenge. The aim of the study was to evaluate patient outcome and potential prognostic factors in this rare presentation of breast cancer. Patients with negative clinical examination, and negative mammogram and ultrasound scan were considered occult (n=95; 1998 to 2010). The median age at diagnosis was 52 years old, and this group consisted 0.87% of all patients treated with breast cancer during the study period. The treatment groups were defined as mastectomy (n=64) + axillary lymph node dissection (ALND), ALND with breast radiotherapy (n=13), and ALND alone (n=18). There were no significant clinicopathological differences between the three groups. Breast MRI was performed for 41patients, which revealed suspicious lesions in 7 patients (of which 5 had histologically confirmed primary breast cancer), Of the 34 patients who had negative MRI, 21 underwent mastectomy. 4/21 was found to have tumour on histological examination. In total primary breast cancer was found in 24/64 mastectomy specimens (20 invasive cancer, and 4 DCIS). With median follow-up of 38.2 months, locoregional relapse free survival (LRFS), recurrence free survival (RFS), and breast cancer specific survival (BCSS) were examined. There were significant differences between the three groups for LRFS (p=0.048), and RFS (p=0.009), but not BCSS (p=0.21). After adjusting for the effects of adjuvant therapy, mastectomy + ALND and breast radiotherapy + ALND had significantly better LRFS (p=0.035 and p=0.042 respectively), and RFS (p=0.044 and p=0.027 respectively) compared to ALND alone. Patients with four or more involved nodes were more likely to suffer from breast cancer specific death and recurrence (p=0.042 and p=0.038 respectively).
European Journal of Surgical Oncology 2012, DOI: 10.1016/j.ejso.2012.08.022
The aim of the study was to identify potential prognostic factors that predict axillary recurrence after a negative sentinel node biopsy (n=929) in a prospective multicentre study (2000 to 2002). Equivalent surgical and pathological examinations were performed between different centres. A median of 2 lymph nodes were removed, and median follow-up was 77 months. 15 patients were diagnosed with axillary recurrence with 5 year axillary recurrence rate of 1.55%. The median disease free survival between surgery and axillary recurrence was 39 months (range 10 to 67 months). 5 year estimated locoregional recurrence rate was 1.89%. Multivariate analysis showed that young age, and absence of radiotherapy to the breast were the most important risk factors in developing axillary recurrence (p=0.007 and p=0.01 respectively). Worse distant metastasis free survival was seen in patients who developed axillary recurrence (p<0.0001), compared to N0 and N1 patients.
European Journal of Surgical Oncology 2012; DOI; 10.1016/j.ejso.2012.04.016
This study investigates outcome after 10 years following two different breast reduction surgery (1997-2000) techniques: vertical scar reduction mammoplasty (n=70) versus inverted T-scar reduction mammoplasty (n=211). The median weight of bilateral resection tissue was 1050g. The median general appreciation score from patients were 8 out of 10, with no difference between the two techniques. At 3 months after surgery, 37% of the patients evaluated as ‘good’ by the Strasser scoring system, 46% mediocre, and 17% poor. After 10 years, this changed to good in 80%, and mediocre in 13%, and poor in 7%. This improvement was statistically significant (p=0.001). Complication rate was 16% with patients requiring scar revisions, and one patient requiring re-reduction surgery. The median patient satisfaction score was 5.5 in those who suffered from complications (p=0.006). Ptosis was seen in quarter of patients at 10 years follow-up.
Authors aimed to assess the outcome of patients operated on using an ultrasound scalpel according to a standardized operative technique before accepting it as a routine procedure. A randomized controlled trial was designed to compare the outcome of patients undergoing breast surgery and axillary dissection using either a standard scalpel blades, scissors, ligations, and electrocautery or the ultrasound scalpel only. Each arm of the trial consisted of 30 patients. A statistically significant benefit in terms of axillary and chest wall drainage volume, the number of axilla seromas, intraoperative bleeding, and hospitalization stay was recorded in the harmonic scalpel group. No significant differences were found between the 2 groups in terms of operative time. Finally, no postoperative hematoma, wound infections, and chest wall seroma were observed.
American Journal of Surgery, October 2012; doi:10.1016/j.amjsurg.2011.06.051
The aim of the study was to investigate the operative mortality and age-related trends in surgical management of breast cancer in the elderly. A total of 5235 patients underwent surgery for breast cancer (1994-2007) during this time. 42% were older than 60 years old, and 20% were older than 70 years old. Patient’s age ranged from 20 to 94 years old. 85% of patients were diagnosed with stage I and II disease, whereas 15% had advanced stage III and IV disease. The mean tumour size was 2 cm for those with invasive carcinoma, and 1.12 cm for those with DCIS. Patients over the age of 70 were more likely to have earlier stage (T1 and T2) tumour (92% vs 87%, p<0.01), smaller tumours (1.6cm vs 1.9cm, p<0.01), lower prevalence of Lymphovascular invasion (27% vs 36%, p<0.01), and lower prevalence of a positive sentinel lymph node (26% vs 31%, p=0.01). There were also higher prevalence of invasive lobular carcinomas in the elderly (12% vs 7%, p<0.01). 65% of patients over 70 years old underwent breast conserving surgery (BCS), which was not significantly different to BCS rate of 62% in those under 70 years old (p=0.16). Bilateral mastectomy rates were significantly higher in those under 70 years old (31% vs. 13%, p<0.01). Analysis of mortality after surgical procedure was performed on day 30 and 90. 30 day mortality for patients over 70 years old was 0.2%. No patients died after 30 days in those under 70 years old. The 90 day mortality for patients over 70 years old was 0.7%, compared to 0.05% for those less than 70 years old.
The Breast Journal 2012, DOI: 10.1111/j.1524-4741.2012.01272.x
This study investigates risk factors and prognosis for developing contralateral breast cancer (CBC). This is a population-based study involving 42670 women diagnosed with breast cancer (1992-2008). Metachronous from synchronous CBC was distinguished using a 6 months interval. After exclusion mainly due to lack of data regarding follow-up, 37393 women were eligible for analysis. The median survival time for women is this study was 6.7 years, with incidence CBC rate of 3.5 per 1000 persons-years. The risk of CBC was almost twice as high with women who had more than 10 positive nodes versus women who were node negative. Extension of cancer to chest wall or skin (T4) more than doubled the risk also. Tumour grade and hormone receptor status was not associated with increased risk of CBC. Lobular histology increased risk (HR 1.3; CI 95% 1.1 to 1.6). Endocrine treatment reduced the risk of developing CBC. Multivariate analysis showed that women diagnosed with CBC within 5 years of initial diagnosis had significantly increased risk of dying from breast cancer, and endocrine therapy reduced the risk of women dying from CBC by one half. The risk of dying from CBC was significantly high for women with younger than 49 years old at initial diagnosis, and for women diagnosed with large CBC and/or positive nodes. The hazard of death was higher for CBC compared to UBC, and this risk did not decrease to the same level until 13 years after the initial diagnosis.
Journal of Clinical Oncology 2012, DOI: 10.1200/JCO.2011.39.3645
The role of acellular dermis in immediate prosthetic breast reconstruction remains unclear, particularly within a radiated field. The authors evaluated and compare outcomes following reconstruction with and without acellular dermis, and analyzed patients exposed to radiation therapy. Retrospective review of 417 consecutive patients (592 breasts) treated from January of 2006 to October of 2008 at one institution was performed. Relevant patient characteristics and follow-up were recorded. Complications were categorized by type and end outcome, including nonoperative, operative, or explantation. Both groups had comparable follow-up (acellular dermis, 23.2 ± 8.9 months; no acellular dermis, 24.4 ± 12.7 months; p = 0.23). Appropriate statistical analyses, including multiple regression, were performed. Acellular dermis patients (n = 199 breasts) had larger body mass indexes (p = 0.0001) and more nipple-sparing mastectomies (p = 0.04) than non–acellular dermis patients (n = 393 breasts). Breasts with acellular dermis had larger intraoperative fill volumes (p < 0.0001) and decreased postoperative expansions (p = 0.02), but no decrease in time to implant exchange. There were no significant differences in complication profiles between acellular dermis and non–acellular dermis breasts, after adjusting for other relevant patient variables on regression analysis. After stratifying patients by exposure to radiation, acellular dermis breasts had a decreased risk of all complications related to radiation as compared with non–acellular dermis breasts.
Plastic & Reconstructive Surgery: October 2012. doi: 10.1097/PRS.0b013e318262f009
Multi-Disciplinary Team (MDT) meeting is mandatory in recommending treatment decisions for patients with newly diagnosed or suspected cancer. This study investigates the implementation of MDT decisions, and factors influencing the decisions. A prospective evaluation of MDT decisions between April and July 2007 at University Hospitals Bristol NHS Foundation trust was performed. The aspects examined included decisions made at diagnostic and therapeutic MDT meetings. There were 317 MDT decisions made in 238 women. 28 were excluded, majority due to unavailable results, and this left 289 decisions in 210 women. MDT decisions were compared to final treatment received by the patient to see if MDT decision was implemented. Majority of decisions were implemented, except 6.9% (n=20) which were changed after the meeting (95% CI: 4.3% to 10.5%). The driving factor behind this was patient choice (n=13). Other major reasons were change in decision by the clinician at the time of the clinic appointment to optimise cosmetic outcome for the patient (n=3), and when new clinical information became available after MDT meeting (n=3). MDT decisions were less likely to be adhered to in patients over 75 years old (p=0.002), and in patients with confirmed malignant disease compared to those with benign disease (p<0.001).
The Breast Journal 2012, DOI: 10.1111/j.1524-4741.2012.01270.x
Using electrocautery significantly reduces blood loss but can increase the risk of seroma and flap necrosis in mastectomy. Ultrasonic dissection devices have been shown to reduce thermal injuries in animal studies. The aim of the systematic review (search up to 2011) was to compare outcome after mastectomy using the two aforementioned techniques. The primary outcomes examined were total post-operative drainage, seroma formation, and intra-operative blood loss. Secondary outcomes examined were operative time, wound complications, and seroma aspiration volumes. Out of 420 potentially relevant publications, 6 were included in the final pooled analysis, which included 287 mastectomies. Mean drainage was 699mls for ultrasonic dissection versus 896ml for electrocautery (p=0.41). There were 49 incidences of seroma development in the ultrasonic dissection group versus 44 in the electrocautery group (p=0.37). The mean blood loss was 236ml in the ultrasonic dissection group versus 365ml in the electrocautery group (p=0.03, with significant statistical heterogeneity in the included studies; p<0.01). The mean operative time was 112 minutes for ultrasonic dissection versus 114 minutes for electrocautery group (p=0.8). There were 13 incidences of wound complication in the ultrasonic dissection group versus 9 in the electrocautery group (p=0.3).
European Journal of Surgical Oncology 2012, DOI:10.1016/j.ejso.2012.05.006
There has been a trend toward limiting perioperative prophylactic antibiotics, based on research not conducted in plastic surgery patients. The authors' university hospital instituted antibiotic prescribing guidelines based on the Surgical Care Improvement Project. An increased rate of surgical-site infections was noted in breast reconstruction patients. The authors sought to determine whether the change in antibiotic prophylaxis regimen affected rates of surgical-site infections. A retrospective study compared patients undergoing breast reconstruction who received preoperative and postoperative prophylactic antibiotics with a group who received only a single dose of preoperative antibiotic. Type of reconstruction and known risk factors for implant infection were noted. Two hundred fifty patients were included: 116 in the pre–Surgical Care Improvement Project group and 134 in the Surgical Care Improvement Project group. The overall rate of surgical-site infections increased from 18.1 percent to 34.3 percent (p = 0.004). Infections requiring reoperation increased from 4.3 percent to 16.4 percent (p = 0.002). Multivariate logistic regression demonstrated that patients in the Surgical Care Improvement group were 4.74 times more likely to develop a surgical-site infection requiring reoperation (95 percent CI, 1.69 to 13.80). Obesity, history of radiation therapy, and reconstruction with tissue expanders were associated with increased rates of surgical-site infection requiring reoperation.
Plastic & Reconstructive Surgery 2012; doi: 10.1097/PRS.0b013e31825dbefe
American College of Surgeons Oncology Group (ACOSOG) Z0010 trial (1999-2003) aimed to evaluate potential predictive factors for recurrences in patients with H&E negative sentinel lymph nodes (SLNs). Eligibility criteria for this multicentre prospective trial included patients with T1-T2, N0, M0 invasive breast cancer who were planned for breast conserving surgery (BCS) with whole breast irradiation. SLNs were assessed for metastasis with standard H&E staining. For patients who had H&E negative SLNs, further immunohistochemistry (IHC) was performed with anti-cytokeratin antibodies. The clinicians were blinded to the IHC results. The incidence of occult metastasis in this group was 10.3%. 5539 patients were recruited from 126 participating sites, and 3904 patients (76.3%) had H&E negative SLNs. Median follow up was 8.4 years. 92.2% of patients completed whole breast irradiation, 43.5% completed adjuvant chemotherapy, and 67.7% completed adjuvant hormonal therapy. There were 127 local, 20 regional, and 134 distant recurrences, and 317 deaths reported. 5 year incidence rates for local recurrence, regional recurrence, and distant recurrence were 2.4%, 0.5%, and 2.8% respectively. There was no difference in recurrence rates between H&E and IHC negative SLNs compared to H&E negative, and IHC positive SLNs. On multivariate analysis, older age (p=0.018, HR 0.98) and positive hormonal status (p<0.0001, HR 0.34) predicted for reduced local failure. Lymphovascular invasion (p=0.008, HR=2), grade 2 disease (p=0.005, HR 2.44), and grade 3 disease (p=0.0003, HR 3.65) predicted for distant recurrences. Older age (p<0.0001, HR 1.07), increasing tumour size (p=0.0013, HR 1.18), and grade III disease (p<0.0001, HR 2.65) predicted for reduced overall survival. When local recurrence was included in the model as a time-dependent variable, older age, T2 disease, higher tumour grade, and local recurrence were associated with reduced overall survival.
Annals of Surgery 2012, DOI: 10.1097/SLA.0b013e3182654494
MRI is used to assess response to neoadjuvant chemotherapy (NAC), and enable potential change in chemotherapy regime with aim to increase tumour volume reduction. This systematic review (up to February 2011) examines the evidence of MRI accuracy in predicting pathological response. A total of 2107 citations were identified with eligibility criteria of studies that enrolled patients with breast cancer who underwent NAC, and MRI performed during NAC. Study-specific estimates of pathological response, sensitivity, and specificity for predicting pathological response were calculated for MRI. Definition of sensitivity included proportion of pathological responders classified as early responder to NAC by MRI. Specificity was defined as the proportion of pathologic non-responders where no early response was detected by MRI. 13 eligible studies were identified (n=605) with median age of 49 years old, invasive ductal carcinoma as the main type, and median of 88% presented with operable disease according to National Surgical Adjuvant Breast and Bowel Project definition (stages IIa, IIb, and IIIa). NAC regimens were anthracycline-based and/or anthracyclines/taxanes-based. MRI was most commonly performed after one or two NAC cycles (nine studies). There was variability in measuring tumour size reduction with majority reporting uni- or bidimensional tumour sizes. Other MRI parameters specific to digital contrast enhanced MRI (DCE-MRI) include dynamic contrast characteristics such as volume transfer constant, exchange rate constant, and early contrast uptake (ECU). Definition of pathological responses varied between the studies with varying definitions of pathological complete response (pCR), and ‘near-pCR’. The latter was defined as small clusters of microscopic residual cancer, or similar definitions of minimal residual disease. This heterogeneity of pathological outcome measures and MRI parameters precluded statistical meta-analysis. Sensitivity and specificity were highest in studies measuring reductions in volume transfer (near-pCR), ECU (pCR), and three dimensional tumour volume (pCR or near-pCR). Lowest sensitivity and specificity were seen in studies measuring reductions in tumour size in uni- or bidimensional tumour sizes.
The Breast 2012, DOI: 10.1016/j.breast.2012.07.006
Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I—III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial
A subcutaneous formulation of trastuzumab has been developed, offering potential improvements in patient convenience and resource use compared with the standard intravenous infusion of the drug. Authors compared the pharmacokinetic profile, efficacy, and safety of the subcutaneous and intravenous formulations in patients with HER2-positive early breast cancer. The HannaH study was a phase 3, randomised, international, open-label, trial in the (neo)adjuvant setting. Patients with HER2-positive, operable, locally advanced or inflammatory breast cancer were randomly assigned to eight cycles of neoadjuvant chemotherapy administered concurrently with trastuzumab every 3 weeks either intravenously (8 mg/kg loading dose, 6 mg/kg maintenance dose) or subcutaneously (fixed dose of 600 mg); 1:1 ratio. Chemotherapy consisted of four cycles of docetaxel (75 mg/m2) followed by four cycles of fluorouracil (500 mg/m2), epirubicin (75 mg/m2), and cyclophosphamide (500 mg/m2), every 3 weeks. After surgery, patients continued trastuzumab to complete 1 year of treatment. Coprimary endpoints were serum trough concentration (Ctrough) at pre-dose cycle 8 before surgery (non-inferiority margin for the ratio between groups of 0·80) and pathological complete response (pCR; non-inferiority margin for the difference between groups of −12·5%), analysed in the per-protocol population. 299 patients were randomly assigned to receive intravenous trastuzumab and 297 to receive subcutaneous trastuzumab. The geometric mean presurgery Ctrough was 51·8 μg/mL (coefficient of variation 52·5%) in the intravenous group and 69·0 μg/mL (55·8%) in the subcutaneous group. The geometric mean ratio of Ctrough subcutaneous to Ctrough intravenous was 1·33 (90% CI 1·24—1·44). 107 (40·7%) of 263 patients in the intravenous group and 118 (45·4%) of 260 in the subcutaneous group achieved a pCR. The difference between groups in pCR was 4·7% (95% CI −4·0 to 13·4). Thus subcutaneous trastuzumab was non-inferior to intravenous trastuzumab for both coprimary endpoints. The incidence of grade 3—5 adverse events was similar between groups. The most common of these adverse events were neutropenia (99 [33·2%] of 298 patients in the intravenous group vs 86 [29·0%] of 297 in the subcutaneous group), leucopenia (17 [5·7%] vs 12 [4·0%]), and febrile neutropenia (10 [3·4%] vs 17 [5·7%]). However, more patients had serious adverse events in the subcutaneous group (62 [21%] of 297 patients) than in the intravenous group (37 [12%] of 298); the difference was mainly attributable to infections and infestations (24 [8·1%] in the subcutaneous group vs 13 [4·4%] in the intravenous group). Four adverse events led to death (one in the intravenous group and three in the subcutaneous group), all of which occurred during the neoadjuvant phase. Of these, two—both in the subcutaneous group—were deemed to be treatment related.
The Lancet Oncology 2012; doi:10.1016/S1470-2045(12)70329-7
Latissimus dorsi (LD) flap is a common form of breast reconstruction, but the incidence of seroma is high at the donor site. Fibrin sealants obliterate transected vessels and lymphatics, and provide haemostasis and tissue adherence. Therefore, it can obliterate the dead space at the donor site to reduce the risk of seroma. This study is a single centre randomised controlled trial investigating the effect of fibrin sealant (Tisseel®) versus no intervention (2006-2010). Outcome measures included total seroma volumes at 3 months after surgery, frequency of aspirations, and incidence of postoperative complications and pain. Patients who were randomised included consecutive women who underwent immediate LD reconstruction, either by LD implant or by extended autologous LD reconstruction. Randomisation was performed using a computer-generated sealed envelope, which was opened by theatre staff during surgery. The study was powered for size effect. All patients were blinded, but not the operating surgeon. Breast care nurses who evaluated the seromas were blinded. The control group (n=53) underwent standard closure without quilting sutures. The fibrin group (n=48) had Tisseel® applied to the upper and lower back. Patient characteristics were comparable in both groups in terms of the extent of reconstruction and the axillary procedures performed. 4 drains were inserted for both groups: 2 at the donor site, one at the breast, and one in the axilla if axillary node dissection was performed. Drain volumes were measured first 7-10 days after surgery, and drains were removed once the output was less than 30-50ml over 24 hours. Clinical review took place at 1 and 2 weeks after surgery, and also at 1 and 3 months after surgery. Decision to aspirate seroma was dependent on its size, and the patient’s symptoms. There was no difference in the outcome between the 2 groups over the 3 months. The drain outputs were not reduced using fibrin sealant in the first 7-10 days after surgery, and the volume of seroma did not differ after the removal of the drains. There were no statistically significant difference between the two groups in terms of complication rates, and pain scores.
British Journal of Surgery 2012, DOI: 10.1002/bjs.8874
Oncoplastic surgery allows oncologically safe breast conservation whilst minimising cosmetic deformities. The authors devised different mammoplasty technique for each quadrant of the breast, and this was applied to 175 consecutive patients (2005-2010). Outcome measures included rate of re-excision, recurrence rates, complication rates, and an objective cosmetic evaluation. Level 1 technique involves excision of less than 20% of breast volume, whereas level 2 techniques involve excision of greater than 20% breast volume. Skin excision with nipple areolar complex re-centralisation is required in the latter. The techniques for each tumour location are outlined as follows: inferior pedicle mammoplasty for upper pole, lateral mammoplasty for upper outer quadrant, J mammoplasty for lower outer quadrant, inverted-T mammoplasty for lower pole, V mammoplasty for lower inner quadrant, and batwing or round block mammoplasty for the upper inner quadrant. Median patient age was 58 years old, and median preoperative tumour size was 25 mm (range 10 to 80 mm). 38 patients underwent neoadjuvant chemotherapy. 116 patients had invasive ductal carcinoma, 25 patients had invasive lobular carcinoma, and 32 patients had ductal carcinoma in situ only. The median weight of the resection specimen was 125g (range 17 to 680 g). Contralateral breast reduction was performed in 26.9% to achieve symmetry. The median tumour size at pathological examination was 25 mm (range 4 to 90 mm). Involved margins were detected at pathological examination in 13.1% of cases (n=23). Patients with DCIS were statistically more likely to have involved margins (p=0.025), compared to other histological subtypes. 17/23 patients underwent subsequent completion mastectomy. Complication rate was 7.4%, and this led to delay in adjuvant treatment for 1.7% of the cohort. All complications were managed in the outpatient setting. With median follow-up of 49 months, 7 patients developed locoregional recurrences, and 11 patients presented with distant metastasis. One patient died in the follow-up period from breast cancer. Cosmetic evaluation was available for 80 patients (45.7%), with mean cosmetic score of 4.6 (excellent, 5; good, 4; fair, 3; poor, 2; bad, 1)
British Journal of Surgery 2012, DOI: 10.1002/bjs.8877
Little is known about the treatment of breast cancer during pregnancy. Authors aimed to determine whether treatment for breast cancer during pregnancy is safe for both mother and child. Authors recruited patients from seven European countries with a primary diagnosis of breast cancer during pregnancy; data were collected retrospectively if the patient was diagnosed before April, 2003 (when the registry began), or prospectively thereafter, irrespective of the outcome of pregnancy and the type and timing of treatment. The primary endpoint was fetal health for up to 4 weeks after delivery. From April, 2003, to December, 2011, 447 patients were registered, 413 of whom had early breast cancer. Median age was 33 years (range 22—51). At the time of diagnosis, median gestational age was 24 weeks (range 5—40). 197 (48%) of 413 women received chemotherapy during pregnancy with a median of four cycles (range one to eight). 178 received an anthracycline, 15 received cyclophosphamide, methotrexate, and fluorouracil, and 14 received a taxane. Birthweight was affected by chemotherapy exposure after adjustment for gestational age (p=0·018), but not by number of chemotherapy cycles (p=0·71). No statistical difference between the two groups was observed for premature deliveries before the 37th week of gestation. 40 (10%) of 386 infants had side-effects, malformations, or new-born complications; these events were more common in infants born before the 37th week of gestation than they were in infants born in the 37th week or later (31 [16%] of 191 infants vs nine [5%] of 195 infants; p=0·0002). In infants for whom maternal treatment was known, adverse events were more common in those who received chemotherapy in utero compared with those who were not exposed (31 [15%] of 203 vs seven [4%] of 170 infants; p=0·00045). Two infants died; both were exposed to chemotherapy and delivered prematurely, but both deaths were thought not to be related to treatment. Median disease-free survival for women with early breast cancer was 70·6 months (95% CI 62·1—105·5) in women starting chemotherapy during pregnancy and 94·4 months (lower 95% CI 64·4; upper 95% CI not yet reached) in women starting chemotherapy after delivery (unadjusted hazard ratio 1·13 [95% CI 0·76—1·69]; p=0·539).
The Lancet Oncology, September 2012, doi:10.1016/S1470-2045(12)70261-9
The authors hypothesised that radiofrequency ablation (eRFA) could reduce the need for further excision of close or positive margins after breast conserving surgery (BCS). The cohort included 73 patients with a tumour size<3 cm, age>50 years old, and those with clinically negative lymph nodes. A standard lumpectomy was performed and then the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity and maintained at 100 °C for 15 min. 19 patients had positive or close margins after the initial BCS and underwent repeat excision. There were 4 ipsilateral recurrences including 1 in-site recurrences at 55 months. There were no regional recurrences. Cosmetic score was rated as excellent or good by 90% of the patients.
Annals of Surgical Oncology 2012, DOI: 10.1245/s10434-012-2476-2
This is a retrospective cohort observational study to examine if there is a benefit of completion axillary lymph node dissection (cALND) in patients who have positive sentinel lymph nodes (SLN). 276 women who had positive sentinel lymph nodes were included. 206 patients underwent cALND and 70 patients did not receive any further axillary surgery. The former group was more likely to undergo mastectomy, receive chemotherapy and have macrometastatic SLN disease. On multivariate analysis, only oestrogen receptor negativity predicted for recurrence. Recurrence rate was 10% for the cALND group, compared to 14% in the no cALND group. There was no axillary recurrence in the latter group. Breast cancer specific death occurred in 2% of patients in the cALND group, compared to 4% in the no cALND group.
Annals of Surgical Oncology 2012, DOI: 10.1245/s10434-012-2547-4
This study describes safe conversion of axillary lymph node dissection (ALND) as a day-case procedure without compromising patient care - excluding patients who underwent concurrent mastectomy or reconstruction surgery. This was devised in the multidisciplinary setting (2009-2010) and involved better education to medical staff and patients, provision of post-operative drain-care instructions, and teaching of upper limb exercise techniques. All patients were called by a nurse within 24 hours of surgery, and any patients with concerning symptoms were called back to the clinic. Drains were removed when the output was less than 30ml in two consecutive days. All complications occurring within 30 days of surgery was recorded prospectively on to a hospital database. Out of 282 patients, 240 patients underwent day-case ALND (85.1%). The re-operation rate was 0.7%; both cases were due to haematomas identified in the post-operative recovery area. Therefore, they did not require re-admission. The re-admission rate was 0.8% in the day-case ALND group. The 30 day complication for the study period was 3.3%. This was comparable to 3.5% in the previous year.
The Breast 2012, DOI: 10.1016/j.breast.2011.10.002
High incidence of breast pain is reported after implant reconstruction and breast augmentation. However, there is a lack of information regarding intercostal neuroma, which occurs as a result of iatrogenic trauma during surgery. The trauma can be due to dissection or traction-related injury, as well as disproportionate implant size related to pocket size. The authors report three cases where patients presented with point tenderness in the intercostals regions. All were successfully treated with local anaesthetic block initially, followed by surgical exploration. During surgery, the identified intercostal nerve was clipped and divided, leading to resolution of pain in these patients. The proximal nerve stump was buried in the surrounding muscle to prevent further neuroma formation.
2012, DOI: 10.1016/j.bjps.2012.04.003
Achieving clear margin is important in breast conserving surgery (BCS) to reduce local and distant recurrence rates. BASO audit in 2008 reported a re-excision rate of 21% following BCS. Although advocated, the efficacy of IOSR is not proven. IOSR enables specimen radiograph to be taken without the need to transfer the specimen to a radiographic facility. The authors evaluated the effect of Faxtron IOSR system on re-excision rate following BCS of palpable lesions. Two surgeons were involved in two 18 months time periods. In the first 18 months, BCS was performed without IOSR (n=111). After a learning period of 1 year, BCS was performed with IOSR for 18 months (n=113). In the latter group, further cavity biopsies were performed when margin compromise was suspected after reviewing the IOSR images. There were no statistical difference between the two groups in terms of tumour size, histological subtypes, and proportion of operations performed by the two surgeons. Prior to IOSR, cavity shaves were performed in 8.4% of cases. After the introduction of IOSR, cavity shaves were performed in 30.8% of cases (p=0.001). Despite this increase, the average total weight of tissue removed was significantly less (p=0.001) in the IOSR group (70.3g) versus the non-IOSR group (110.2g). However, there were no differences in the re-excision rates between the two groups after histological analysis (p=0.65).
The Breast 2012, DOI: 10.1016/j.breast.2011.10.010
Lower pole breast cancers pose a problem in terms of cosmesis following breast conserving surgery (BCS) and radiotherapy. One solution to this is an oncoplastic technique that uses a de-epithelialized submammary fasciocutaneous flap to fill the lumpectomy cavity, called the ‘Crescent’ technique. The authors report the outcome of 54 patients who underwent BCS using this technique (mean follow-up of 45 months). Inclusion criteria included women with small (cup size A/B) or medium (cup size C) sized breasts, and lower pole tumour (invasive carcinoma or DCIS) close to the inframammary fold. All patients were followed up on a yearly basis with clinical examination and mammograms. Both patients and surgeons rated cosmetic outcome on a yearly basis. This was performed using a global scale from 5 to 1 (5= excellent, to 1= poor). Mean age of patients was 54.2 years old. 13% of patients had cup size A, 57% had cup size B, and 30% had cup size C. 83% of patients had T1c tumour, compared to 13% with T1a or b tumour, and 4% with T2 tumour. The mean pathological tumour size was 15.7mm (range 3-50). 5/54 patients were found to have involved lateral margins on histopathological examinations, and underwent completion mastectomy. The remaining 49 patients went on to receive radiotherapy to the breast. 6 patients required drainage of seroma, and 3 of these patients developed wound infection. Only one patient developed haematoma that required surgical evacuation. No local recurrence was detected during the follow-up period, but two patients developed contralateral cancer and one died from metastatic disease. 6/49 patients were found to have fat necrosis on subsequent mammograms. Cosmetic results were reported as excellent or good in 74% of patients, and only one patient requested contralateral surgery for symmetrisation.
The Breast 2012, DOI: 10.1016/j.breast.2011.11.004
Dissection with electrocautery has the advantage of reduced blood loss, but can result in longer operative time, and may increase the risk of flap necrosis due to elevated temperature in the surrounding tissues. Tumescence technique involves injection of local anaesthetic and crystalloid into subcutaneous tissue to enable bloodless sharp dissection. This may also result in faster operative time. The aim of study was to investigate patient outcome between the two techniques. The outcome measure involved wound infection, flap necrosis, and haematoma. This was a retrospective study involving 134 patients who underwent mastectomy (2007-2011): electrocautery technique was used exclusively from 2007 to 2009 (64 patients), and tumescence technique from 2009 to 2011 (70 patients). The rate of immediate breast reconstruction (IBR) was 57.8% in the electrocautery group, compared to 65.7% in the tumescence group (p=0.35). The overall complication rate was 21.6% (23.4% in the electrocautery group vs. 20% in the tumescence group, p=0.63). However, higher flap necrosis was seen with tumescence technique (8.6%) vs. electrocautery (1.6%). Although not statistically significant (p=0.07), this was deemed clinically significant. Moreover, all the patients who suffered from flap necrosis in the tumescence group underwent IBR. Logistic regression was performed to identify potential predictors for post-operative complication, and the following factors were found not to be significant: age, bilateral surgery, neoadjuvant therapy, lymph node status, co-morbidities, smoking status, BMI, and surgical technique (tumescence vs. electrocautery). Only IBR was significantly associated with post-operative complication (odds ratio 12.95, p<0.001).
Annals of Surgical Oncology 2012;DOI:10.1245/s10434-012-2304-8
There is increasing trend towards intra-operative diagnosis of sentinel lymph node (SLN) metastasis. Conventionally this involves H&E histopathological examination of frozen sections, and then the definitive diagnosis is made postoperatively by further histopathological examination. H&E examination of a single section has low sensitivity however, and although step sectioning can reduce the false negative rate, this is costly and time-consuming. Alternative approaches involve molecular detection of metastasis using quantitative reverse transcription PCR (QRT-PCR). Based on this technique the authors developed a novel rapid quantitative genetic assay, termed transcription-reverse transcription concerted reaction (TRC). This assay detects cytokeratin (CK19) and carcinoembryogenic antigen (CEA) mRNA level, which was used for intra-operative rapid (30-40 minutes) diagnosis of SLN metastasis. Sensitivity and specificity was determined against the gold-standard of post-operative histopathological diagnosis. The assay was also compared to the conventional intra-operative frozen section examinations. The study involved 131 patients with early stage breast cancer (264 SLNs). The study involved training and validation sets (2007-2010). There were no significant differences between the two groups in terms of the clinicopathological characteristics. The assay results from the first 50 patients were used to determine the cut-off value of CK19 mRNA to define metastasis. Then this value was used for the next 81 patients to evaluate the validity of the assay. Overall, there were 46 metastasis (36 macrometastasis and 10 micrometastasis). The metastasis-positive rate was 11% by intra-operative frozen section examination compared to 17.4% by postoperative histopathological examinations. The overall concordance rate between the two examinations was 93.6%. However, the sensitivity was only 63% for the frozen section examination, resulting in 17 false-negative intra-operative examinations. In comparison, CK19/CEA double markers achieved sensitivity of 97.1%, specificity of 99.2%, and concordance rate of 99.4% when used against the validation set. Moreover, mean copies of CK19 and CEA increased with the size of metastasis. Using combined cut-offs for CK19/CEA, accuracy of 91.3% was achieved in distinguishing micrometastasis against macrometastasis.
British Journal of Cancer 2012;DOI:10.1038/bjc.2012.300
A detailed understanding of the anatomy of pectoral nerves is important in axillary dissection and axillary breast augmentation amongst others. Its damage can lead to atrophy of the pectoral muscles. The aim of the study was to provide detailed anatomy of the pectoral nerves, and to allow easier intra-operative identifications of these nerves. The authors dissected 26 brachial plexuses from 15 fresh cadavers. Axillary dissection was performed to identify the superior, middle, and inferior branches of the pectoral nerves and its relationship to the pectoralis major muscle. In all dissections 3 constant branches were identified. In 77% of cases the superior and the middle branches arose separately at trunk level, but they arose from the same origin in the remaining 23% of cases. The anatomical relationships were further classified into A1, A2, and B. In A1 (62%), the superior and the middle branches arose separately from trunk but were connected by an ansa. In A2 (15%), the superior and middle branches arose separately and were not connected. In B (23%), the superior and middle branches arose from the same origin. These findings are against the classical anatomical description that states that pectoralis major muscle is innervated by two nerves: superior and middle branches as a single nerve (lateral pectoral nerve) and the inferior branch (medial pectoral nerve). Injury to the middle and the inferior branch can occur during surgical access to the pocket during axillary breast augmentation, and lead to atrophy of the pectoralis major muscle. These branches are also closely associated with axillary central and anterior lymph nodes, and can be damaged during axillary dissection. Injury to a single branch is almost undetectable functionally, but injury to both the branches can have serious functional consequences. The superior branch is generally not injured during the surgical procedures mentioned due to its anatomical location.
Routine hospital follow-up is recommended after primary treatment for breast cancer to enable early detection of new primary breast cancer. Current Dutch guideline involves 5 years of hospital follow-up with yearly mammogram. This workload can be reduced by less frequent follow-up, and follow-up of shorter duration. Follow-up can also be provided by general practitioners (GP) and nurses. The authors used a previously validated simulation model to evaluate the effectiveness in detecting early breast cancer and costs of the different follow-up strategies. The alternative strategies involved combinations of shift in care to GP after 2 years of hospital follow-up, lowering referral age to national screening programme (NSP), and by terminating yearly physical examination in general practice. The input population was based to Dutch women diagnosed with breast cancer from 1989 to 2003 (n=5073). This simulation was used due to lack of adequate trial data. The model included population death rates, risk of developing new primary breast cancer, sensitivity of breast examination, specificity of mammogram and clinical examination, and patient’s compliance. A total of 141 tumours were detected in simulation, compared to 136 tumours in the Dutch database. The current strategy showed no significant difference in tumour detection rate compared to the alternative strategies. The alternative strategies showed lower mean screening cost also (3.16 to 3.98 million euro) compared to 4.3 million euro for the current strategy.
British Journal of Surgery 2012;DOI: 10.1002/bjs.8850
Recent trials have shown that radiotherapy after breast conserving surgery (BCS) may be of minimal benefit for older patients who have lower baseline risk of local recurrence. The trial data led to change in National Comprehensive Cancer Network guideline in the to state that radiotherapy may be omitted in patients older than 70 years old who have stage I breast cancer and are receiving endocrine therapy. However, patients treated in trial may differ to patients in general population, and it is unknown whether radiotherapy may be omitted in the older patients who do not meet the guidelines. The authors used population-based data to determine the clinicopathological factors associated with failure to preserve the breast in the long-term. These factors were used to create a nomogram which predicted the likelihood of breast preservation with and without radiotherapy. The cohort was selected from a SEER database (1992 to 2002) with analysis limited to patients between 66 to 79 years old (n=16092) who received BCS with median follow-up of 7.2 years. In total 3.1% of patients underwent subsequent mastectomy, with overall 5- and 10-year mastectomy free survival of 98.1% and 95.4% respectively. Multivariate analysis showed that age less than 74 years old, black race, tumour size> 2cm, negative ER status, nodal status, and non-receipt of radiotherapy were predictive of time to mastectomy. These factors were incorporated into developing a nomogram to predict 5- and 10-year mastectomy free survival (MFS). The nomogram was internally validated using the bootstrap validation method, resulting in a concordance index of 0.66. This compares favourably to other well established breast cancer-specific risk predictors.
Journal of Clinical Oncology 2012;DOI: 10.1200/JCO.2011.41.0076
Sentinel lymph node biopsies (SLNB) are currently performed using dual technique of blue dye and radiocolloid. Disadvantages of the latter include cumulative exposure to radiation, and also some units use blue dye alone due to the lack of access to nuclear medicine. Therefore, this study investigates the role of ICG (a non-radioactive tracer), which sends out fluorescence signal to enable detection of the SLN. Fluorescence-based tracer also allows visualisation of the subcutaneous lymphatic. This has the advantage of providing a real time navigation, and hence assisting the surgeon with surgical localisation of the SLN. A total of 100 patients were recruited in non-randomised manner and underwent SLNB using combination of blue dye and radiocolloid, as well as ICG as a third tracer. In total 242 lymph nodes were removed, and out of these 201 were defined as true SLN (blue and/or hot). 100% of these nodes were ICG positive, 95% were both ICG positive and blue, 77.6% were both ICG positive and radioactive, and 73.1% were identified with all tracer methods. No serious adverse events were reported with the use of ICG.
European Journal of Surgical Oncology 2012;DOI:10.1016/j.ejso.2012.05.007
In patients who develop unilateral breast cancer, the risk of developing contralateral breast cancer is 0.3-1% per year. Despite this low risk, there is increasing trend for contralateral prophylactic mastectomy (CPM). The authors compared patients who chose CPM (n=177) versus those who had unilateral mastectomy (n=178) with the aim of determining patient characteristics and survival outcomes. The latter group was randomly selected to match for age and tumour stage. The data was collected retrospectively from a prospective database (1995-2008). Patient characteristics collected for included age, race, preoperative MRI, previous biopsies, family history, BRCA gene mutation, or past history of breast cancer. Tumour characteristics collected for included histology, size, grade, lymph node status, Multifocality/multicentricity, and hormonal status. Treatment characteristics included type of surgery, and modalities of adjuvant treatments. There was no statistical difference in the two groups regarding histology, grade, Multifocality, or hormone receptor status, and tumour size. CPM patients were more likely to undergo preoperative MRI (p<0.001). With respective to the MRI findings, additional suspicious foci were more often found in the CPM patients (p=0.038). More patients in the CPM group had family history (p<0.0001), BRCA gene mutation (p=0.043), and previous biopsies (p=0.001). There was no statistical difference in the two groups in terms of adjuvant treatment profile. More patients in the CPM group underwent nipple preserving surgery (p<0.0001) and immediate breast reconstruction (p<0.0001). 11/177 CPM patients (6.6%) were found to have occult breast cancer in the contralateral breast. 3/178 patients (1.7%) who only underwent unilateral mastectomy went onto develop contralateral breast cancer (median follow-up of 61 months). Uni- and multivariate analysis did not show that CPM patients had better survival or disease-free survival.
Annals of Surgical Oncology 2012;DOI: 10.1245/s10434-012-2299-1
Frequency of lymphoedema after axillary lymph node dissection (ALND) varies considerably, and although several risk factors have been identified, it is difficult to estimate the risk for the individual patient. The aim of the study was to create a validated nomogram to assess the risk of developing lymphodema after ALND. The study cohort involved patients (n=1054) who underwent level I, II, or III ALND (2001-2002). The patients were seen in clinic 30 days after surgery, and 6 monthly thereafter for total of 60 months. Each time patients were asked to complete a questionnaire assessing; arm volume measurements, demographic data, body mass index, level of ALND and number of days with drain, use of radiotherapy and endocrine therapy, ipsilateral arm chemotherapy infusions, tumour characteristics including number of involved nodes and the total number of removed nodes, and adverse events (infection, haematoma, and seroma). Lymphoedema was defined if the operated side had volume at least 200ml greater than the non-operated side after 6 months. Online tool (www.armvolume.com) was created to calculate this difference. The overall 5 year cumulative incidence of lymphoedema was 30.3%. 3 models were created for the nomogram; model 1 for preoperative use, model 2 for <6 months after surgery, and model 3 for >6months after surgery. Multivariate analysis showed that all factors were significantly associated with development of lymphodema for the 3 models, except level of ALND for model 1. When the nomograms were used for the validation set, the concordance indices were 0.706, 0.729, and 0.736 for model 1, 2, and 3, respectively. The concordance indices are identical to the area under the receiver operating characteristics (ROC) curve.
Annals of Surgical Oncology 2012;DOI: 10.1245/s10434-012-2290-x
The aromatase inhibitor anastrozole inhibits estrogen synthesis. Fulvestrant binds and accelerates degradation of estrogen receptors. Authors hypothesized that these two agents in combination might be more effective than anastrozole alone in patients with hormone-receptor (HR)–positive metastatic breast cancer. Postmenopausal women with previously untreated metastatic disease were randomly assigned, in a 1:1 ratio, to receive either 1 mg of anastrozole orally every day (group 1), with crossover to fulvestrant alone strongly encouraged if the disease progressed, or anastrozole and fulvestrant in combination (group 2). Patients were stratified according to prior or no prior receipt of adjuvant tamoxifen therapy. Fulvestrant was administered intramuscularly at a dose of 500 mg on day 1 and 250 mg on days 14 and 28 and monthly thereafter. The primary end point was progression-free survival, with overall survival designated as a prespecified secondary outcome. The median progression-free survival was 13.5 months in group 1 and 15.0 months in group 2 (hazard ratio for progression or death with combination therapy, 0.80; 95% confidence interval [CI], 0.68 to 0.94; P=0.007 by the log-rank test). The combination therapy was generally more effective than anastrozole alone in all subgroups, with no significant interactions. Overall survival was also longer with combination therapy (median, 41.3 months in group 1 and 47.7 months in group 2; hazard ratio for death, 0.81; 95% CI, 0.65 to 1.00; P=0.05 by the log-rank test), despite the fact that 41% of the patients in group 1 crossed over to fulvestrant after progression. Three deaths that were possibly associated with treatment occurred in group 2. The rates of grade 3 to 5 toxic effects did not differ significantly between the two groups.
N Engl J Med 2012; 367:435-444
Radiation therapy (RT) after lumpectomy for breast cancer can be delivered with several different regimens. We evaluated a cost-minimization strategy to select among RT options. An institutional review board (IRB)-approved retrospective review identified a sample of 100 women who underwent lumpectomy for invasive or in situ breast cancer during 2009. Post lumpectomy RT options included: no radiation in women ≥70 years [T1N0, estrogen receptor (ER)+] per Cancer and Leukemia Group B (CALGB) 9343 (no-RT), accelerated external-beam partial-breast irradiation (APBI), and Canadian fractionation (C-RT), as alternatives to standard whole-breast radiation therapy (WBRT). Eligibility for RT regimens was based on published criteria. RT costs were estimated using the 2011 US Medicare Physician Fee Schedule and average Current Procedural Terminology (CPT) codes billed per regimen at our institution. Costs were modeled in a 1,000-patient theoretical cohort. Median patient age was 56.5 years (range 32–93 years). Tumor histology included invasive ductal cancer (78 %), ductal carcinoma in situ (DCIS) (15 %), invasive lobular cancer (6 %), and mixed histology (1 %). Median tumor size was 1 cm (range 0.2–5 cm). Estimated per-patient cost of radiation was US$5,341.81 for APBI, US$9,121.98 for C-RT, and US$13,358.37 for WBRT. When patients received the least expensive radiation regimen for which they were eligible, 14 % received no-RT, 44 % received APBI, 7 % received C-RT, and 35 % defaulted to WBRT. Using a cost-minimization strategy, estimated RT costs were US$7.67 million, versus US$13.36 million had all patients received WBRT, representing cost savings of US$5.69 million per 1,000 patients treated.
Annals of Surgical Oncology 2012;DOI:10.1245/s10434-012-2546-5
Phyllodes tumors (PTs) are rare breast tumors that usually occur in middle-aged women. Here we discuss our recent experiences in the diagnosis, surgical management, and clinical follow-up of this disease. Authors retrospectively reviewed 164 patients with PTs who underwent surgical treatment at the Department of Surgery, Samsung Medical Center, Seoul, Korea, from January 1995 to July 2009. Clinical and histopathological data were analyzed. The median follow-up period was 33.6 months (range 2–179 months), and the median patient age was 43 years (range of 11–72 years). Tumor size ranged from 1 to 30 cm, with a median of 6.1 cm. A total of 148 patients (90.2 %) received local or wide excisions. Mastectomies were performed in 16 patients (9.8 %). The pathologic diagnoses included 82 benign (50.0 %), 42 borderline (25.6 %), and 40 malignant PTs (24.4 %). The tumor border was infiltrating in 43 patients (26.2 %) and pushing in 116 patients (70.7 %). The resection margin was divided by based on the width. Local recurrence was observed in 31 patients (18.9 %), and distant metastasis developed in four patients with malignant PTs. Risk factors for the local recurrence of a PT were a positive resection margin (P = .029) and tumor size (P = .001).
Annals of Surgical Oncology 2012;DOI:10.1245/s10434-012-2307-5
The authors compared the outcomes of two-stage, acellular dermal matrix (AlloDerm)-assisted prosthetic breast reconstruction including different timings of radiotherapy. A review of two-stage, AlloDerm-assisted, prosthetic breast reconstructions from 2004 to 2010 was performed. All data were recorded prospectively and the study population was stratified by the timing of radiotherapy. Complications were analyzed following first- and second-stage reconstruction. The Spear-Baker classification of capsular contracture was modified for irradiated devices. Reconstructive failure was defined as nonelective removal of a breast prosthesis. AlloDerm-assisted prosthetic reconstruction was performed in 289 women (428 breasts). After first-stage reconstruction, clinically significant capsular contracture rates (grade III/IV) were higher in the radiation therapy during expansion group and in the radiation therapy before mastectomy group compared with the no–radiation therapy group. Three hundred fifty-three breasts (85.9 percent) successfully underwent second-stage reconstruction, with a median follow-up of 15.2 months. Of those 353 breasts, clinically significant capsular contracture (grade III/IV) was highest in the radiation therapy during expansion group. More often than in the other groups, the radiation therapy during expansion group failed two-stage reconstruction and required flaps in addition or as replacement.
Plastic & Reconstructive Surgery, July 2012, doi: 10.1097/PRS.0b013e3182547a45
The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated no difference in overall survival or local–regional recurrence rates between patients planned for breast conservation therapy including whole breast irradiation (WBI) with one or two positive sentinel lymph nodes (SLNs) randomly selected to undergo axillary lymph node dissection (ALND) versus no further surgery. The current study was undertaken to evaluate the impact of Z0011 on surgical practice nationally. A survey was sent by e-mail to 2,759 members of the American Society of Breast Surgeons (ASBrS). Questions assessed the respondents’ practice, familiarity with Z0011, and preferences for treating patients with one or two positive SLNs. Of those surveyed, 849 (30.8 %) responded. The majority (97 %) indicated familiarity with the data. Of those respondents, 468 (56.9 %) would not routinely perform ALND in patients planned to receive WBI, while 279 (36.0 %) would consider omission of completion ALND in patients planned to receive accelerated partial breast irradiation (APBI), and 218 (26.6 %) would consider omission of ALND in patients not planned to receive radiation. Academic and private practice surgeons were equally likely to incorporate Z0011 into practice.
Annals of Surgical Oncology 2012; DOI: 10.1245/s10434-012-2523-z
Authors aim was to compare the accuracy of magnetic resonance imaging (MRI) and ultrasonography (US) in measuring the size of invasive breast cancer (IBC) and carcinoma in situ (CIS). They examined the utility of routinely performing MRI in addition to US before breast-conserving surgery (BCS). Data from 1558 consecutive patients diagnosed with IBC and/or CIS between 2003 and 2005 were reviewed. For comparing the accuracy of US and MRI, paired t test was done comparing pathologic and imaging (US and MRI) tumor size in 821 patients who received both breast US and MRI. In instance of attempted BCS (n = 794), operative approach, resection margins, and clinical outcomes of non-MRI and MRI groups were compared. For CIS, IBC without CIS, and IBC with CIS, MRI was more accurate in estimating tumor size than US. When BCS was attempted (n = 794), the rate of tumor involvement in initial resection margins did not differ between non-MRI and MRI groups (23.0% and 23.4%, P = .926). Similarly, rates of re-excision (13.1% vs 17.5%, P = .130) and conversion to mastectomy (2.3% vs 2.1%, P = .893) were comparable, as were ipsilateral breast tumor recurrence, locoregional recurrence, and disease-free survival (log rank P = .284, .950, and .955, respectively).
Annals of Surgical Oncology 2012; DOI: 10.1245/s10434-012-2289-3
Surgical site infections (SSI) are a source of significant postoperative morbidity and cost. Although immediate breast reconstruction after mastectomy has become routine, the data regarding the incidence of SSI in immediate breast reconstruction is highly variable and series dependent. This study used the National Surgical Quality Improvement Program database to identify all female patients undergoing mastectomy, with or without immediate reconstruction, from 2005 to 2009. Only “clean” procedures were included. The primary outcome was incidence of SSI within 30 days of operation. Stepwise logistic regression analysis was used to identify risk factors associated with SSI. A total of nearly fifty thousand mastectomies were performed during the study period, of which 20% had immediate breast reconstruction. The incidence of SSI was 3.5% in patients undergoing mastectomy with reconstruction and 2.5% in patients undergoing mastectomy without reconstruction (P < 0.001). Independent risk factors for SSI include increased preoperative body mass index (BMI), heavy alcohol use, ASA (American Society of Anesthesiologists) score greater than 2, flap failure, and operative time of 6 hours or longer.
Annals of Surgery 2012;doi: 10.1097/SLA.0b013e3182602bb7
The aim of this study was to predict presence of invasive component and nodal involvement in women diagnosed preoperatively with ductal carcinoma in situ (DCIS) by vacuum-assisted breast biopsy (VABB). Retrospective analysis of 733 patients with preoperatively diagnosed DCIS, investigating the association of clinical–radiological variables with invasive component and nodal involvement. Mammographic size >20 mm and residual lesion on post-VABB mammogram were related to invasive component (both p < 0.0001) and nodal involvement (p = 0.001, p = 0.03). Age <40 years was associated with presence of invasive component (p = 0.003). By multivariate analysis residual disease was associated with invasive component, and mammographic tumor size >20 mm with nodal involvement, both highly significant.
The Breast 2012;doi:10.1016/j.breast.2012.06.009
Bilateral breast reduction is an established procedure performed to relieve the physical pain and psychological discomfort associated with heavy, pendulous breasts. Numerous techniques have been developed over the years with several refinements to obtain safe nipple-areola complex transposition and harmonious breast shape. Based on the experience of the senior author (M.P.), the three dermoglandular flap technique is proposed to achieve a safe and aesthetically pleasing breast reduction through the surgical concept of dermal support. The authors analyzed the benefits of the three dermoglandular flap technique performed in a selected group of smoking patients with a potentially high risk of postoperative complications and high probability of breast ptosis recurrence (each patient had breast volume >1000 cc, breast nipple ptosis grade 3 on Regnault's scale, and body mass index >27). Blood supply to the nipple-areola complex was based on an inferior-central pedicle. Between 1995 and 2007, 47 smokers underwent bilateral breast reduction using the three dermoglandular flap technique. Their ages ranged from 37 to 63 years (mean, 49 years), and their average body mass index was 31.2 kg/m2 (range, 27 to 38). The overall complications rate was 14.9 percent. No wound breakdowns and no complete or partial necrosis of the nipple-areola complex was observed. Follow-up ranged from 18 to 48 months (mean, 32 months).
Plastic and Reconstructive Surgery 2012;doi:10.1097/PRS.0b013e31823ae90c
The purpose of this study was to evaluate the accuracy of axillary ultrasound and ultrasound-guided fine needle aspiration cytology (FNAC) in the preoperative diagnosis of axillary metastases. Between 2004 and 2009, 1132 female patients were evaluated and treated for histologically proven breast carcinoma. Preoperative axillary ultrasound with subsequent FNAC in case of suspicious lymph nodes was performed in 1150 axillae (18 bilateral breast carcinomas). The results of axillary ultrasound and FNAC were analysed retrospectively. Pathological node status was used as the reference standard (based on axillary dissection or sentinel node biopsy). Axillary ultrasound showed suspicious lymph nodes in 327 axillae (28.4%). FNAC showed axillary metastases in 107 of these 327 axillae. Final histological analysis confirmed 106 metastases (one false positive). Histological analysis showed metastatic disease in 429 of 1150 axillae (37.3%). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of axillary ultrasound alone were 43.8% (188/429), 80.7% (582/721), 57.5% (188/327) and 70.7% (582/823), respectively. When combining axillary ultrasound with FNAC of suspicious lymph nodes, sensitivity was 24.7% (106/429), specificity was 99.9% (720/721), PPV was 99.1% (106/107) and NPV was 69.0% (720/1043).
The Breast 2012;21(4):578-583
First-line surgical options for early stage breast cancer and ductal carcinoma in situ include breast conserving surgery or mastectomy. In this study factors were analyzed that influence the receipt of mastectomy and resultant trends over time. Registry analysis was carried out for 21,869 women who underwent up-front surgical treatment for stage 0, I or II breast cancer between 1998 and 2007 using data from the Kentucky Cancer Registry. The trend of treatment over time was examined and assessed the probability of receiving mastectomy using multivariate logistic regression. Overall, 54.5% of women received breast conservation and 45.5% received mastectomy over a 10-year period (annual BCS rate range: 46.9–61.2%). The overall mastectomy rate substantially decreased from 53.1% in 1998 to 38.8% in 2005 (p < 0.0001), but then increased to 45% in 2007 (p < 0.001). Between 2005 and 2007, the increase in mastectomies in the age groups of <50 years, 50–69 years, and ≥70 years was 7.5% (p = 0.0351), 4.9% (p = 0.0132) and, 8.0% (p = 0.0283), respectively. On multivariate analysis, the rate of receiving mastectomy was drastically higher for women with stage I or II (versus in situ) disease and moderate or poorly differentiated (versus well differentiated) histology. The rate was modestly higher for uninsured and government-insured (versus privately insured) patients, patients older than 70 years (versus younger), rural (versus urban) location, receptor negative (versus receptor positive) disease, and unusual histologies (versus ductal and lobular histology). There was no statistically significant difference in surgical choice with regard to race.
The Breast Journal 2012;18:318–325
Lymphoedema of the upper limb is a well-recognised complication of axillary surgery for breast cancer. Effective long-term treatment of lymphoedema by liposuction has previously been demonstrated. In this study authors present first five years of experience using this technique in treatment of upper limb lymphoedema. A prospective analysis of the results of 12 patients who underwent liposuction followed by compression therapy for chronic unilateral upper limb oedema with up to five years of follow-up was carried out. Hospital Anxiety and Depression Score questionnaires and a Visual Analogue Score for overall well-being were also completed pre- and post-operatively. The mean duration of lymphoedema was seven years (range, 1–14), commencing at a mean of one year (range, 0–5) after axillary surgery. The mean excess arm volume at admission was 1391 ml and the ratio of the lymphoedematous to the unaffected arm was 1·48. The mean total aspirate volume was 1713 ml, of which 87 percent was fat. At one year the mean percentage volume reduction compared with the normal arm was 101 percent, meaning that the volume of both of patients’ arms was virtually equivalent, and this reduction was stable with up to 5 years of follow-up. Postoperatively there were reductions in anxiety (p < 0.05) and depression scores, and an improvement in overall well-being.
Journal of Plastic, Reconstructive & Aesthetic Surgery 2012;65(7);935-942
Cutaneous recurrences of breast cancer may cause considerable discomfort due to ulceration, oozing, and pain and can also be difficult to treat. Electrochemotherapy is a localised anticancer treatment using electric pulses to make cell membranes permeable, augmenting uptake of chemotherapeutic drugs, and thus enabling highly efficient tumour cell kill. This is the first systematic investigation of electrochemotherapy for larger cutaneous recurrences of breast cancer. This is a phase II trial for patients with cutaneous recurrences where no further treatment options were available. Primary endpoint was objective response evaluated by clinical examination. Secondary endpoints included response evaluated by PET/CT, change in lung diffusion capacity, patient reported symptoms, and distress related to bodily appearance. Treatment consisted of bleomycin injection followed by application of electric pulses. Seventeen heavily pre-treated patients received electrochemotherapy. Twelve patients were evaluable (follow-up > 8 weeks). CT showed four (33%) patients achieving over 50% tumour volume reduction, clinical examination showed one CR and one PR (OR 17%). Symptomatic relief included decreasing exudates, odour, and bleeding. Treatment was well tolerated; the main side effect was post-treatment pain.
Acta Oncologica 2012; doi:10.3109/0284186X.2012.685524
Fertility preservation is an important survivorship issue for women treated for breast cancer. The aim of this work was to examine the referral practices of health care professionals who treat women with breast cancer in the United Kingdom, and to investigate their understanding and knowledge of the fertility preservation options available. In this study an invitation to participate in a confidential, online questionnaire was e-mailed to surgeons, oncologists, and clinical nurse specialists who manage patients with breast cancer in the United Kingdom. There were 306 respondents. Factors which influenced whether fertility preservation options were discussed with a patient included the following: patient's age (78%), final tumor/nodes/metastasis (TNM) status (37.9%); concern that fertility preservation would delay chemotherapy (37.3%); whether the patient had children (33.5%) or a partner (24.7%); estrogen receptor expression (22.6%), lack of knowledge regarding the available options (20.9%); and concern that fertility preservation would compromise the success of cancer treatment (19.8%). Twenty-seven percent did not know whether fertility preservation was available for their patients on the National Health Service. Nearly half (49.4%) of respondents said that gonadotropin-releasing hormone agonists were used for fertility preservation outside the setting of a clinical trial. Knowledge regarding the available options varied according to different members of the multidisciplinary team, with consultant oncologists better informed than consultant surgeons or clinical nurse specialists (p < .05).
The Oncologist 2012; doi:
There are two main surgical techniques for managing the tumour bed after breast cancer excision. Firstly, closing the defect by suturing the cavity walls together and secondly leaving the tumour bed open thus allowing seroma fluid to collect. There is debate regarding which technique is preferable, as it has been reported that a post-operative seroma increase post-operative infection rates and late normal tissue side effects. Data from 648 patients who participated in the Cambridge Breast IMRT trial were used. Seromas were identified on axial CT images at the time of radiotherapy planning and graded as not visible/subtle or easily visible. An association was sought between the presence of seroma and the development of post-operative infection, post-operative haematoma and 2 and 5 years normal tissue toxicity (assessed using serial photographs, clinical assessment and self assessment questionnaire). The presence of easily visible seroma was associated with increased risk of post-operative infection (OR = 1.80; p = 0.004) and post-operative haematoma (OR = 2.1; p = 0.02). Breast seroma was an independent risk factor for whole breast induration and tumour bed induration at 2 and 5 years. The presence of breast seroma was also associated with inferior overall cosmesis at 5 years. There was no significant association between the presence of seroma and the development of either breast shrinkage or breast pain.
Eur J Surg Oncol. 2012 Jun 13. [Epub ahead of print]
This is a retrospective study investigating 18 F-FDG uptake by the primary tumour as a predictor for relapse and survival. Two hundred and three patients with cT1-T3N0 breast cancer were analysed. Standardised Uptake Value (SUVmax) was measured on the primary tumour. After a median follow up of 68months ( range 22-80), the relation between SUVmax and tumour factors, disease free survival (DFS) and overall survival (OS) was investigated. In PET positive patients, the median FDG uptake by the tumour was 4.7. FDG uptake was significantly related to tumour size, number of involved axillary lymph nodes, grade, negative ER, high Ki-67 and HER2 over expression. No distant metastases or deaths occurred in the PET-negative group. Five-year DFS was 97% and 83%, respectively in the PET-negative and PET-positive groups (P=0.096). At univariate analysis, DFS was siginificantly lower in patients with SUVmax > 4.7 compared to the patients with negative PET(P=0.042),but not to the patients with SUVmax ≤4.7(P=0.106). At multivariate analysis, among PET-positive patients, SUVmax was not an independent prognostic factor for DFS[HR>4.7vs≤4.7:1.02(95%CI0.45-2.31)]. Five-year OS was 100% and 93%, respectively in the PET-negative and PET-positive groups( P=0.126).
The Breast 2012; doi:10.1016/j.breast.2012.05.009
The identification of circulating tumour cells correlate with poor prognosis in metastatic breast cancer, but there are few data describing the importance of circulating tumour cells in patients with non-metastatic disease. Our aim was to establish if circulating tumour cells predicted worse outcome in patients with non-metastatic breast cancer. In this study, data on circulating tumour cells at the time of definitive surgery from chemonaive patients with stage 1—3 breast cancer was collected prospectively from February, 2005, to December, 2010. All patients with operable breast cancer presenting at The University of Texas MD Anderson Cancer Center (Houston, TX, USA) were eligible. Patients were ineligible if they had bilateral breast cancer or any other malignancy within 5 years of the diagnosis of the present cancer. Circulating tumour cells were measured with the CellSearch System (Veridex, Raritan, NJ) and correlated findings of circulating tumour cells with standard tumour characteristics, including tumour size and grade; oestrogen and progesterone receptor and human epidural growth factor receptor 2 (HER2) status; and axillary lymph node status with χ2 or Fisher exact tests. Outcomes were assessed at a median follow-up of 35 months. In 73 (24%) of 302 patients, one or more circulating tumour cells were identified and detection of one or more circulating tumour cells predicted both decreased progression-free survival (log rank p=0.005;hazard ratio 4.62;95% CI 1.79-11.9) and overall survival (log rank p=0.01;HR 4.04, CI 1.28-12.8).
Lancet Oncology 2012; doi:10.1016/S1470-2045(12)70209-7
Reduction mammoplasty (RM) continues to be popular. The reported incidence of occult breast carcinoma in these specimens varies between 0.05 and 1.8 %. Literature review reveals a wide discrepancy in study methodology, outcome measures, and even what is constituted as a “significant” result. In this study authors try to identify RM patients at increased risk of occult significant pathological findings to engender a systematic improvement in efficiency of those specimens sent for histopathological examination. A single-centre retrospective study of the pathology results for 1,388 consecutive RM patients was undertaken. Patients were divided into three groups according to indication for surgery: group 1, macromastia; group 2, developmental asymmetry; and group 3, symmetrising surgery after breast cancer reconstructive surgery. Nine cases of occult carcinoma were found among the 1,388 women (0.65 %), all in patients over 35 years of age. Forty percent of all patients were under 35 years old. Histopathological analysis of 59 % of patients revealed nonsignificant findings. Patients with a breast cancer history were 4.3 times more likely to have occult breast cancer. Patients under 30 years of age had a significantly higher chance of nonsignificant findings than those over 30 (relative risk = 2.5).
Aesthetic Plastic Surgery 2012;DOI: 10.1007/s00266-012-9919-9
More than half the patients who undergo axillary node dissection (AND) due to positive sentinel lymph nodes (SLN) do not reveal any further positive nodes when histological examination is carried out. Various predictors are available to assist clinical decision making in these patients with aim to spare unnecessary AND. The aim of this study was to compare the predictive models and assess their variability. The study cohort involved 120 patients who went on to have completion AND. In total 9 predictive models were evaluated including: MSKCC, Cambridge, Stanford, Mayo, MOU, Gur, MDA, Tenon, and Saidi. For nomograms <10% was chosen as the threshold for low risk for additional non-SLN metastasis. In this cohort 68% of patients were found to have no further positive nodes at completion AND. Overall, 64.2% of the cohort was considered low risk by at least one of the nine prediction models. However, box plot for the nomograms showed that distribution of the predicted probabilities vary greatly. Even at individual level great variability existed between the predictive models. Furthermore, the use of the predictive models may alter with findings from the AMAROS trial, and Z0011 trial from ACOSOG.
Annals of Surgical Oncology 20120; DOI:10.1245/s10434-011-2169-2
There is a rising incidence of breast cancer in women under the age of 45 years old. Preservation of fertility in these women may represent a dilemma since hyperestrogenic effect of pregnancy may negatively affect the prognosis. The aim of the study was to investigate whether pregnancy after breast cancer worsens prognosis. All women under the age of 36 years old who were diagnosed with breast cancer were included (n=115 with mean follow-up of 44.5 months). 18/115 patients became pregnant during the follow-up period. 8/18 patients decided to terminate pregnancy and the remaining 10 gave birth successfully. The clinical and histological characteristics were not statistically significant between the pregnant and the non-pregnant group. Adjuvant treatment were similar in the two groups, but hormonal treatment was significantly more frequent in the non-pregnant group (p=0.01).
At 5 year follow-up 100% of the pregnant group was alive, compared to 80% in the non-pregnant group. The percentage of disease-free patients were 94% for the pregnant group, compared to 64% in the non-pregnant group (p=0.009).
The Breast 2012; DOI:10.1016/j.breast.2011.10.001
This study measures the impact of the addition of full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) on the accuracy of mammography in a population of women recalled following film-screening mammography alone. Women recalled for assessment following routine screening with screen-film mammography participated in the study. Participants underwent bilateral two view FFDM and two view DBT. Readers scored each lesion separately for probability of malignancy on screen-film mammography, FFDM and DBT. These scores were compared with the presence or absence of malignancy based on the final histopathological outcome.
738 women participated in the study. following assessment 204 (26.8%) were diagnosed as malignant (147 invasive and 57 in situ cancers), 286(37.8%) as benign and 269(35.4%) as normal. The diagnostic accuracy was evaluated by using receiver operating characteristic (ROC) and measurement of area under curve (AUC). This demonstrated a significant (p=0.0001) in the diagnostic accuracy with addition of DBT combined with FFDM and film-screen mammography (AUC =0.9671) when compared to FFDM plus screen film mammography (AUC=0.8949) and screen film mammography alone (AUC=0.7882). The effect was significantly greater for soft tissue lesions [(AUC=0.9905 with addition of DBT and AUC was 0.9201 for FFDM with screen-film mammography combined ( p=0.0001)] compared to microcalcification [ with addition of DBT (AUC=0.7920) and form FFDM with screen film mammography combined (AUC=0.7843;p=0.3182)]
Clinical Radiology 2012, DOI;10.1016/j.crad.2012.03.009
This study evaluates the use of 3-D surface imaging to evaluate breast symmetry in an objective manner. 3-D surface scanner (Konica-Minolta Vivid 910) was used, and captured images were converted in to a single virtual 3-D model using appropriate software. Standardisation and precision analysis of the breast symmetry evaluation across different observers were carried out on 2 dummy models of differing breast volume. 3 observers independently carried out 3-D evaluation 10 times on both dummies (n=60). Then the same 3 observers carried out 3-D evaluation 10 times on 10 test volunteers (n=300). No significant intra- or inter-observer difference was detected for both dummies and for test volunteers (p>0.05 for all pairwise comparisons). Finally 3-D evaluation was performed on 15 patients who had breast augmentation and on 15 who had breast reduction. This was performed pre- and post-operatively. The 3 observers carried out 5 evaluations per patient (n=900). This result was compared to the 2-D BCCT.core software by analysing breast area difference (BAD) between the left and right breast. 3-D evaluation enabled more precise anatomical landmark setting than 2-D, and enabled more accurate assessment of BAD.
The Breast 2012; DOI; 10.1016/j.breast.2011.07.016
Acellular dermal matrix (ADM) provides lower pole support in patients undergoing implant based reconstruction. This retrospective study compares outcome in patients undergoing reconstructions using Alloderm (n=126) versus Strattice (n=144). The latter is a porcine based product, and is less expensive. All operations were performed by a single surgeon. With the mean follow-up of 18.2 months, total complication rate in the Alloderm group was 21.4%. This included seroma rate of 12.7%, explantation rate of 2.4%, and infection rate of 2.4%. With the mean follow-up of 14.4 months, total complication rate in the Strattice group was 6.3%; with seroma rate of 1.4%, explantation rate of 1.4%, and infection rate of 2.1%. The overall complication rate was significantly lower in the Strattice group (p=0.0003). However, when seroma was excluded the overall complication rate was not significantly different between the two groups.
Plastic and Reconstructive Surgery 2012; DOI; 10.1097/PRS.0b013e31824ec429
This retrospective study compares the percentages and mammographic features of cancers missed at full-field digital mammography (FFDM) and screen-film mammography (SFM) in women who participated in the Norwegian Breast Cancer Screening Program in 2002-2008. Cases selected were all the interval and screening detected cancers from 35127 FFDM and 52444 SFM examinations in two Norwegian Counties. Prior Diagnostic FFDM examinations of 49 interval and 86 screening detected breast cancers were reviewed by four breast radiologists and compared with a review of SFM examinations of 81 interval and 123 screening detected cancers. Cancers were classified as true or missed, mammographic features were described and percentages were compared. The percentages of interval and screening detected cancers missing at FFDM and SFM did not differ significantly. Interval cancers missed were 33% (16 of 49) at FFDM vs 30% (24 of 81) at SFM with a P value of 0.868. Screening cancers missed 20% (17 of 86) at FFDM vs 21% (26 of 123) at SFM (P-value 0.946). Asymmetry was present in 27% of prior mammograms of cancers missed at FFDM and 10% of those missed at SFM ( P value=0.070). Calcifications were observed in 18% of cancers missed at FFDM and 34% of those missed at SFM (p-value = 0.185). Average mammographic tumour size of missed cancers manifesting as masses was 10.4mm at FFDM and 13.6mm at SFM (p-value=0.036).
Radiology 2012; d10.1148/radiol.12112074
This paper in the Annals of Surgical Oncology reviews the training experience of Society of Surgical Oncology (SSO)-approved fellowship in breast oncology (2005-2009) via an electronic survey. The fellowship arose to meet the need for advanced subspecialty training in breast surgery. This included exposure to training in breast imaging, breast surgery, genetics, medical and radiation oncology, pathology, plastic and reconstructive surgery, and research. 85/142 (60%) graduates from the fellowship responded to the survey. 98% felt well prepared for performing breast cancer surgery. 53% felt well prepared to perform oncoplastic techniques, and 39% felt well prepared to perform ultrasound (28% for ultrasound guided biopsies). 76% of the graduates dealt exclusively with breast disease. 14% were director of breast centre, with only 29% in private practice. 67% had received at least three job offers and 82% were satisfied or very satisfied in their current jobs.
Annals of Surgical Oncology 2012; DOI; 10.1245/s10434-011-2164-7
This prospective cohort study in Plastic & Reconstructive Surgery examines the rate of post-operative complications in patients who underwent nipple sparing mastectomy (NSM) followed by expander-implant based immediate breast reconstruction (IBR) with or without acellular dermal matrix (ADM) at a single centre. Alloderm was the chosen ADM. The first cohort involved 90 consecutive cases where ADM was not used (2006-2007). The second cohort involved 100 cases where ADM was used for all cases consecutively (2007-2008). The last cohort involved 260 cases where ADM was used selectively for thinner mastectomy skin flaps (2008-2010). There were no significant differences in the risk factors between the three cohorts, and the mean follow-up was 25.5 months. Infection rate was 27.8% in the consecutive non-ADM group, 20% in the consecutive ADM group, and 15.8% in the selective ADM group (p=0.04). Unplanned return to theatre was 23.3% in the consecutive non-ADM group, 11% in the consecutive ADM group, and 10% in the selective ADM group (p=0.004). Expander-implant loss was 17.8% in the consecutive non-ADM group, 7% in the consecutive ADM group, and 5% in the selective ADM group (p=0.001).
Plastic & Reconstructive Surgery 2012; DOI; 10.1097/PRS.0b013e31824ec447
In this randomised, double blind, parallel group, multicentre, phase 3 trial published in the Lancet,oestrogen receptor positive, Her-2 negative premenopausal breast cancer patients were randomised to receive 3.6mg/month plus either anastrozole 1mg per day and tamoxifen placebo or tamoxifen 20mg per day and anastrozole placebo for 24 weeks before surgery. The primar endpoint was overall tumour response assessed by callipers. Between 2007 and 2009, 204 patients were enrolled. More patients in the anastrozole group had complete or partial response than did in those in the tamoxifen group during 24 weeks of neoadjuvant treatment ( Anastozole 70.5% vs Tamoxifen 50.5%, with an estimated difference between groups 19.9% , 95% CI 6.5-33.3;p=0.004) Two patients in anastrozole group reported grade 3 adverse events( arthralgia and syncope) and so did one patient in tamoxifen group( depression).
The Lancet Oncology, 2012; doi:10.1016/S1470-2045(11)70373-4
Prognostic Value of Number of Removed Lymph Nodes, Number of Involved Lymph Nodes, and Lymph Node Ratio in 7502 Breast Cancer Patients Enrolled onto Trials of the Austrian Breast and Colorectal Cancer Study Group (ABCSG)
Based on a large cohort of patients from four prospective clinical trials of the Austrian Breast and Colorectal Cancer Study Group (ABCSG), this study investigates the potential prognostic value of number of involved nodes (NIN), number of removed nodes (NRN), and ratio of involved to removed nodes (lymph node ratio, LNR) in breast cancer. Total of 7052 patients underwent axillary lymph node dissection (ALND); 4334 patients (61.5%) were node negative, compared to 2718 patients who were node positive (38.5%). Analysis was performed in the latter group. No correlation was found between NRN and prognosis. Univariate and Multivariate analysis showed that increasing LNR and NIN were significantly associated with worse recurrence-free survival and overall survival (p<0.001).
Annals of Surgical Oncology 2012; DOI; 10.1245/s10434-011-2189-y
Increasingly numbers of Nipple-Sparing Mastectomy (NSM) are being performed. However, this gives rise to the possibility of local recurrence in the form of Paget’s disease, but this incidence remains unknown. The authors report 7 cases of Paget’s disease local recurrence after 861 NSM (2002-2008). The median follow-up time was 50 months. All patients underwent intraoperative frozen section examination to confirm the absence of malignancy in the retroareolar margins, and all received electron beam intraoperative radiotherapy (ELIOT). Primary carcinoma with ductal intraepithelial neoplasia or invasive ductal carcinoma with extensive in situ component, negative hormone receptor status, high pathological grade, and HER2 overexpression were significantly associated with increasing Paget’s disease local recurrence. Paget’s disease local recurrence rate was 0.8% (7/861 cases). However, among the recurrence on the NAC, Paget’s disease local recurrence represented 63.8% (7/11 cases)
Annals of Surgical Oncology 2012; DOI; 10.1245/s10434-012-2226-5
Elderly patients with breast cancer differ in terms of tumour biology, co-morbidities, and are underrepresented in clinical trials. The aim of the study was to assess adherence to national breast cancer treatment guidelines according to age, and examine age-specific survival in relation to adherence to treatment guidelines. The study is based on Netherlands Cancer Registry database (2005-2008), and examines patients with early breast cancer (T0-2 N0-1 M0). Two age groups were examined; those <65 years old (n-24959) vs those>75 years old (n=6561). Median follow-up for all patients was 2.8 years. Compared to those <65 years old, greater proportion of patients >75 years old did not undergo surgery, and were less likely to receive chemotherapy or radiotherapy. However, endocrine treatment was more likely to be administered in these >75 years old. 62% of patients <65 years old adhered to treatment guidelines, as opposed to 55.6% of patients >75 years old (p<0.001). 5 treatment modalities were investigated for; breast surgery, axillary surgery, endocrine treatment, chemotherapy, and radiotherapy. Majority of patients in both groups received at least three modalities of treatment in accordance to the guidelines: 93.8% for those >75 years old vs 98.8% for those <65 years old. However, survival analysis using the instrumental variable showed that adherence to guidelines was not significantly associated with overall survival in both groups.
British Journal of Surgery 2012; DOI; 10.1002/bjs.8743
Current National Comprehensive Cancer Network (NCCN) recommendations suggest that minimum 10 axillary lymph nodes should be collected via level I or II axillary nodal dissection (AND) to accurately stage the axilla. However, there are evidences to suggest that axillary lymph node yield is reduced for patients undergoing neoadjuvant chemotherapy (NAC) compared to those who undergo primary surgery only. The aim of the study was to evaluate whether NAC reduces total lymph node yield after AND. Retrospective analysis was performed on patients who underwent AND from 2000 to 2008. 240 patients underwent AND after NAC, compared to 903 patients who underwent primary AND. In the NAC group median of 15 lymph nodes were removed (range 1-46), compared to median of 17 lymph nodes in the control group (range 2-64). There was a statistically significant difference between the 2 groups (p=0.0003). The authors attribute this reduction to fibrosis in the axillary nodes after NAC. Extensive fibrosis can increase the difficulty of AND, and may no longer be identifiable in the surgical specimen.
Annals of Surgical Oncology 2012; DOI; 10.1245/s10434-011-2199-9
Predict (www.predict.nhs.uk) is an online tool that gives indications to breast cancer prognosis and treatment benefit for individual patients. Predict+ includes prognostic effect of HER2 status. The aim of the study was to compare 10 year survival estimates from Predict+ to the original Predict model and Adjuvant!, as well as comparing it to the observed 10 year outcome from British Columbia dataset (n=1653). The latter was used previously to validate Predict and Adjuvant! Estimates for the prognostic effect of HER2 were based on 14017 breast cancer patients from 15 studies in the Breast Cancer Association Consortium. 10 year predicted Overall Survival (OS) and Breast Cancer Specific Survival (BCSS) were calculated for Predict+, Predict, and Adjuvant! by investigators blinded to actual patient outcome. Predicted outcome from the 3 models were compared to the observed outcome from the British Columbia dataset. OS predicted by Adjuvant! was within 6.1% of the observed compared to 8.8% for Predict, and 8.4% for Predict+. BCSS predicted by Adjuvant! was within 14% of the observed compared to 3.6% for Predict, and 2.5% for Predict+. In patients with HER2 positive tumours, BCSS predicted by Predict+ was within 4% of the observed compared to 20% for Predict, and 29% for Adjuvant!
The Breast 2012;21:151
Implant rupture is a well recognised complication, and investigations range from clinical examination to the use of USS and MRI. The aim of the study was to establish sensitivity and specificity for the three modalities, and delineate relative/respective roles for each investigation. This is a retrospective study based on patients who underwent investigations by all three modalities from 2005 to 2007 (n=60). 12 implants were found to be ruptured at surgery, giving rupture rate of 20% in the study period. Clinical examination had a sensitivity of 42% and specificity of 50%. USS had a sensitivity of 50% and specificity of 90%. MRI had a sensitivity of 83% and specificity of 90%. Concordance rate between USS and MRI was 87%, coming to the same diagnostic conclusion in 52/60 implants.
The Breast Journal; DOI; 10.1111/j.1524-4741.2012.01226.x
This study examines the progression of arm lymphoedema (ALE) in patients treated with breast conserving surgery (BCS) for early stage breast cancer, and aimed to identify potential risk factors for progression of ALE. The study sample consisted of 266 patients (stage I and II) who received BCS and Axillary nodal dissection followed by radiotherapy. Lymphoedema was classed into mild, moderate, or severe category according to the differences in arm circumference between the treated and untreated sides; 0.5-2cm (mild), 2.1-3cm (moderate), and >3cm (severe) respectively. On initial presentation 41% had mild, 47% had moderate, and 12% had severe lymphoedema. However, after median follow-up of 56 months, 34% of the cohort had upgraded to a more severe grade of lymphoedema. Univariate and multivariate analysis showed that risk factors for progression included age older than 65 years old at presentation (p=0.04) and regional lymph node irradiation (p=0.001). Progression was not influenced by BMI, number of lymph nodes removed, or time from treatment of breast cancer to the development of initial lymphoedema.
The Breast Journal 2012; DOI; 10.1111/j.1524-4741.2012.01229.x
Skin sparing mastectomy (SSM) allows preservation of skin envelope and improves cosmesis in immediate breast reconstruction. Large series has not revealed higher local recurrence rates following SSM. There is limited data regarding residual breast tissue (RBT) after SSM however. This study examines the rate of RBT after SSM, its oncological implications, and investigates for potential contributing factors. Out of 92 patients who had SSM, 66 had skin specimens removed subsequently for non-oncological reasons. Mean volume of excised skin was 93.9cm3. Pathological analysis of the removed skin specimen showed that 6% had RBT (4/66). No recurrences have been detected in this group after median follow up of 33.5 months. Age, BMI, tumour size, and oestrogen receptor status did not contribute to increased risk of RBT.
The Breast Journal 2012; DOI; 10.1111/j.1524-4741.2012.01234.x
The presence of variant anatomy in the axilla can increase the risk of iatrogenic injury. This study examines the frequency and nature of this variance based on in vivo preoperative surgical observations. Prospective recording was made during consecutive axillary dissections. Variance in the anatomy of thoracodorsal (TD) pedicle, lateral thoracic vein (LTV), latissimus dorsi muscle slips, axillary and angular vein, and of the intercostobrachial nerve (ICBN) were recorded. Total of 73 axillary dissections were observed, and in 59% at least one anatomical variation was observed. Notable variation included aberrant course of the TD nerve (14%); LTV (16%); bifid axillary veins (14%); and variations in ICBN origins and branching was seen in 36%.
British Journal of Surgery 2012; DOI; 10.1002/bjs.8737
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