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Nipple-sparing mastectomy (NSM) is being performed increasingly for risk reduction in high-risk groups. There are limited data regarding complications and oncological outcomes in women undergoing bilateral prophylactic NSM. This study reviewed institutional experience with prophylactic NSM, and examined the indications, rates of postoperative complications, incidence of occult malignant disease and subsequent breast cancer diagnosis.Women who had bilateral prophylactic NSM between 2000 and 2016 were identified from a prospectively maintained database. Rates of postoperative complications, incidental breast cancer, recurrence and overall survival were evaluated.A total of 192 women underwent 384 prophylactic NSMs. Indications included BRCA1 or BRCA2 mutations in 117 patients (60·9 per cent), family history of breast cancer in 35 (18·2 per cent), lobular carcinoma in situ in 29 (15·1 per cent) and other reasons in 11 (5·7 per cent). Immediate breast reconstruction was performed in 191 patients. Of 384 NSMs, 116 breasts (30·2 per cent) had some evidence of skin necrosis at follow-up, which resolved spontaneously in most; only 24 breasts (6·3 per cent) required debridement. Overall, there was at least one complication in 129 breasts (33·6 per cent); 3·6 and 1·6 per cent had incidental findings of ductal carcinoma in situ and invasive breast cancer respectively. The nipple-areola complex was preserved entirely in 378 mastectomies. After a median follow-up of 36·8 months, there had been no deaths and no new breast cancer diagnoses.These findings support the use of prophylactic NSM in high-risk patients. The nipples could be preserved in the majority of patients, postoperative complication rates were low, and, with limited follow-up, there were no new breast cancers.La mastectomía con preservación del pezón (nipple-sparing mastectomy, NSM) se realiza cada vez más para reducir riesgos en los grupos de pacientes de alto riesgo. Se dispone de pocos datos sobre complicaciones y resultados oncológicos en mujeres sometidas a NSM bilateral profiláctica. Este estudio revisó la experiencia institucional de la NSM profiláctica, y analizó las indicaciones, tasas de complicaciones postoperatorias, incidencia de enfermedad maligna oculta y diagnóstico de subsiguiente cáncer de mama. MÉTODOS: Se identificaron mujeres sometidas a NSM bilateral profiláctica durante el periodo 2000-2016 a partir de una base de datos prospectiva. Se evaluaron tasas de complicaciones postoperatorias, cáncer de mama incidental, recidiva y supervivencia global.Un total de 192 mujeres fueron sometidas a 384 NSMs profilácticas. Las indicaciones incluyeron mutaciones BRCA1 o BRCA2 en 117 (61%) pacientes, historia familiar de cáncer de mama en 35 (18%), carcinoma lobulillar in situ en 29 (15%) y otros motivos en 11 (5,7%). La reconstrucción mamaria inmediata se realizó en 191 pacientes. De las 384 NSMs, 116 (30%) presentaron alguna evidencia de necrosis de la piel durante el seguimiento y la mayoría se resolvieron de forma espontánea, con solo 24 (6,2%) mamas que requirieron desbridamiento. Globalmente hubo al menos una complicación en 129 (34%) mamas; 3,6% y 1,6% tuvieron hallazgos incidentales de carcinoma ductal in situ o cáncer de mama invasivo, respectivamente. El complejo areola-pezón se preservó completamente en 378 mastectomías. Tras una mediana de seguimiento de 36,8 meses, no hubo fallecimientos ni ningún diagnóstico nuevo de cáncer de mama. CONCLUSIÓN: Estos hallazgos apoyan la utilización de la NSM profiláctica en pacientes de alto riesgo. En la mayoría pacientes fue posible la preservación del pezón, las tasas de complicaciones postoperatorias fueron bajas y, con un seguimiento limitado, no hubo nuevos casos de cáncer de mama.

Background Young age at breast cancer diagnosis is associated with negative prognostic outcomes, and breast cancer in black women often manifests at a young age. This study evaluated the effect of age on breast cancer management and outcomes in black women. Methods This was a retrospective cohort study of all black women treated for invasive breast cancer between 2005 and 2010 at a specialized tertiary-care cancer centre. Clinical and treatment characteristics were compared by age. Kaplan–Meier methodology was used to estimate overall survival (OS) and disease-free survival (DFS). Results A total of 666 black women were identified. Median BMI was 30 (range 17–56) kg/m2 and median tumour size was 16 (1–155) mm. Most tumours were oestrogen receptor-positive (66·4 per cent). Women were stratified by age: less than 40 years (74, 11·1 per cent) versus 40 years or more (592, 88·9 per cent). Younger women were significantly more likely to have a mastectomy, axillary lymph node dissection and to receive chemotherapy, and were more likely to have lymphovascular invasion and positive lymph nodes, than older women. The 5-year OS rate was 88·0 (95 per cent c.i. 86·0 to 91·0) per cent and the 5-year DFS rate was 82·0 (79·0 to 85·0) per cent. There was no statistically significant difference in OS by age (P = 0·236). Although DFS was inferior in younger women on univariable analysis (71 versus 88 per cent; P < 0·001), no association was found with age on multivariable analysis. Conclusion Young black women with breast cancer had more adverse pathological factors, received more aggressive treatment, and had worse DFS on univariable analysis. Young age at diagnosis was, however, not an independent predictor of outcome.

Nipple-sparing mastectomy (NSM) is increasingly performed for invasive breast cancer. Growing evidence supporting the oncologic safety of NSM has led to its widespread use and broadened indications. In this study, we examine the indications, complications, and long-term outcomes of therapeutic NSM. From 2003 to 2016, women undergoing NSM for invasive cancer or ductal carcinoma in situ (DCIS) were identified from a prospectively maintained database. Patient and disease characteristics were compared by procedure year, while complications were compared by procedure year using generalized mixed-effects models accounting for a random surgeon effect. Overall survival and time to recurrence were examined. Of the 467 therapeutic NSMs, 337 (72%) were invasive cancer, 126 (27%) were DCIS, and 4 (1%) were phyllodes tumors. Median age was 45 years (range 24–75) and median follow-up among survivors was 39.4 months. Three hundred and fifty-seven (76.4%) cases were performed in 2011 or after. When comparing NSMs performed before and after 2011, there was a significant increase in NSMs performed for invasive tumors (58% vs. 77%; p

Women with dense breasts may have less-accurate preoperative evaluation of extent of disease, potentially affecting the achievement of negative margins. The goal of this study is to examine the association between breast density and re-excision rates in women having breast-conserving surgery for invasive breast cancer. Women with stage I/II invasive breast cancer treated with breast-conserving surgery between 1/1/2014 and 10/31/2014 were included. Breast density was assessed by two radiologists. The association between breast density and re-excision was examined using logistic regression. Seven hundred and one women were included. Overall, 106 (15.1%) women had at least one re-excision. Younger age at diagnosis was associated with increased breast density (p

Among patients with a core biopsy diagnosis of ductal carcinoma in situ (DCIS), approximately 10% have microinvasion (DCISM), which, like DCIS, is subject to upstaging by surgical excision, but for which the rates of T and N upstaging are unknown, as is the role of sentinel lymph node biopsy (SLNB), since current studies of SLNB for DCISM are based on the final pathologic report, not the core needle biopsy. In this study, we identified the rates of T and N upstaging following surgical excision in patients with a suspected versus definite core needle biopsy diagnosis of DCISM. Overall, 369 consecutive patients (2007–2017) with a core biopsy diagnosis of suspected versus definite DCISM and surgical excision were stratified by extent of DCISM on core biopsy: suspicious focus, single focus, multiple foci/single biopsy, and multiple foci/multiple biopsies. Within strata, we identified clinicopathologic features associated with T and N upstaging. Across core biopsy strata, there were no clear differences in imaging characteristics or median invasive tumor size (0.2 cm). Among 105 patients with a core biopsy suspicious for DCISM versus 264 with definite DCISM, 28% and 37%, respectively, were upstaged to at least pT1a, but only 1% and 6%, respectively, to pN1. Although 28% of patients with suspected DCISM on core biopsy were surgically upstaged to invasive cancer, the frequency of pN1 SLN metastasis (1%) was comparable with that of DCIS, and was insufficient to recommend SLNB at initial surgery. SLNB remains reasonable for patients with definite DCISM on core biopsy.

The efficacy of chemoprevention for breast cancer risk reduction has been demonstrated in randomized controlled trials; however, use remains low. We sought to determine whether uptake differed by risk factors, and to identify reasons for refusal and termination. Women seen in a high-risk clinic from October 2014 to June 2017 considered eligible for chemoprevention (history of lobular carcinoma in situ, atypia, family history of breast/ovarian cancer, genetic mutation, or history of chest wall radiation) were retrospectively identified. Breast cancer risk factors were compared among those with and without chemoprevention use, and compliance was noted. Overall, 1506 women were identified, 24% with prior/current chemoprevention use. Women ≥ 50 years of age were more likely to use chemoprevention than women

BACKGROUND: BRCA mutation carriers have an elevated lifetime breast cancer risk and remain at risk for interval cancer development. We sought to compare BRCA mutation carriers with screen-detected versus interval breast cancers. METHODS: Women with a known BRCA mutation prior to a breast cancer diagnosis were identified. Clinical and pathologic factors, and imaging within 18 months of diagnosis were compared among screen-detected versus interval cancers. Interval cancers were those detected by physical exam among women undergoing regular screening. RESULTS: Of 124 breast cancers, 92 were screen and 22 clinically detected, of which 11 were interval cancers among regular screeners, and 10 were incidentally found on prophylactic mastectomy. Women with interval cancers were younger, had lower body mass indexes, and were more likely to be Black than those with screen-detected cancers (p

Background Both patients with inflammatory breast cancer (IFLBC) and patients with noninflammatory T4 breast cancer (non-IFLBC) have a heavy disease burden in the breast; whether the unique biology of IFLBC conveys a higher locoregional recurrence (LRR) risk and worse outcomes in comparison with other T4 lesions is uncertain. Here the outcomes of patients with IFLBC and patients with non-IFLBC treated with modern multimodality therapy are compared. Methods Patients with nonmetastatic T4 breast cancer treated with neoadjuvant chemotherapy, mastectomy, and radiation therapy between 2006 and 2016 were identified. Recurrences and survival were compared between patients with IFLBC and patients with non-IFLBC overall and stratified by receptor subtype. Results For 199 T4 patients, the median age was 52 years, and the median clinical tumor size was 7 cm. One hundred seventeen (59%) had IFLBC. With a median follow-up of 41 months, 4 patients had isolated LRR; all cases occurred in patients with IFLBC. The 5-year isolated LRR rate for patients with IFLBC was 4.8%. Overall, 14 patients had both LRR and distant recurrence (DR); 47 had DR only. The 5-year distant recurrence-free survival (DRFS) rates were similar for patients with IFLBC and patients with non-IFLBC (63% vs 71%; log-rank P = .14). The 5-year DRFS rate was lowest among triple-negative (TN) patients (43%) and was significantly lower for patients with TN IFLBC versus patients with non-IFLBC (28% vs 62%; log-rank P = .02). The 5-year overall survival rates (71% vs 74%; log-rank P = .4) and cancer-specific survival rates (74% vs 79%; log-rank P = .23) did not differ between IFLBC and non-IFLBC. Conclusions Although IFLBC is often considered a unique biologic subtype, patients with IFLBC and patients with non-IFLBC had similar outcomes with modern multimodality therapy; isolated LRR was uncommon. The TN subtype in patients with IFLBC is associated with poor outcomes, and this indicates the need for new treatment approaches in this group.

BACKGROUND. Low incidence of breast cancer in men (BCM) (65 years). Kaplan-Meier methods were used to compare overall survival (OS) and breast cancer-specific survival (BCSS). Competing-risk methods analyzed time to second primary cancers (SPCs), with any-cause death treated as a competing risk. RESULTS. The study identified 152 BCM patients with a median age of 64 years (range, 19–96 years). The median body mass index (BMI) was 28 kg/m(2). Men age 65 years or younger (n = 78, 51 %) were more overweight/obese than men older than 65 years (n = 74, 49 %) (89 % vs 74 %, respectively; P = 0.008). Both groups had similar nodal metastases rates (P = 0.4), estrogen receptor positivity (P = 1), and human epidermal growth factor receptor 2 (HER2)neu overexpression (P = 0.6). Men 65 years of age or younger were more likely to receive chemotherapy (P = 0.002). The median follow-up period was 5.8 years (range, 0.1–14.4 years). The 5-year OS was 86 % (95 % confidence interval [CI], 80–93 %), whereas the 5-year BCSS was 95 % (95 % CI, 91–99 %). The BCM patients 65 years of age and younger had better OS (P = 0.003) but not BCSS (P = 0.8). The 5-year cumulative incidence of SPC was 8.4 % (95 % CI, 3.4–13.4 %). The prior SPC rate was higher for men older than 65 years (n = 20, 31 %) than for those age 65 years or younger (n = 7, 11 %) (P = 0.008). This did not account for differences in life years at risk. No difference was observed in SPC cumulative incidence stratified by age (P = 0.3). CONCLUSIONS. Men 65 years of age or younger received more chemotherapy and had improved OS, but not BCSS compared with men older than 65 years. For all BCM, SPC is a risk, and appropriate screening may be warranted.

INTRODUCTION: Nipple-sparing mastectomy (NSM) is increasingly used for breast cancer risk reduction and treatment. Prior small studies with variable control for baseline characteristics suggest superior satisfaction with NSM. The aim of this study was to compare patient satisfaction following NSM and total mastectomy (TM) utilizing the BREAST-Q patient-reported outcome measure in a well-characterized patient population. METHODS: Patients at a single institution undergoing NSM or TM with immediate tissue expander/implant reconstruction who completed a follow-up BREAST-Q from 2007–2017 were identified by retrospective review of a prospective database. Baseline characteristics were compared, and linear mixed models were used to analyze associations with BREAST-Q scores over time. RESULTS: Of 1866 eligible patients, 219 (12%) underwent NSM, and 1647 (88%) underwent TM. Median time from baseline to BREAST-Q was 658 days. Patients having NSM were younger, more likely to be white, and had lower BMI. They more often had prophylactic surgery, bilateral mastectomies, lower-stage disease, and less often received chemotherapy/radiation than patients having TM. On multivariable analysis, after controlling for relevant clinical variables, there was no difference in satisfaction with breasts or satisfaction with outcome overall between NSM and TM patients. Psychosocial well-being and sexual well-being were significantly higher in the NSM group. After additionally controlling for pre-operative BREAST-Q score in a subset of patients (72 NSM; 443 TM), only psychosocial well-being remained significantly higher in NSM patients. CONCLUSION: Patient-reported outcomes should be discussed with women weighing the risks and benefits of NSM to provide a better understanding of expected quality of life.

Guidelines concur that postmastectomy radiation therapy (PMRT) in T1-2 tumors with one to three positive (+) lymph nodes (LNs) decreases locoregional recurrence (LRR) but advise limiting PMRT to patients at highest risk to balance against potential harms. In this study, we identify the risks of LRR after mastectomy in patients with T1-2N1 disease, treated with modern chemotherapy, and identify predictors of LRR when omitting PMRT. Patients with T1-2N1 breast cancer undergoing mastectomy between 1995 and 2006 were categorized by receipt of PMRT. The Chi square test compared the clinicopathologic features between both groups, and Kaplan–Meier and Cox regression analysis was used to determine the rates of LRR, recurrence-free survival (RFS), and overall survival (OS). Overall, 1087 patients (924 no PMRT, 163 PMRT) were included in the study, with a median follow-up of 10.8 years (range 0–21). We identified 63 LRRs (56 no PMRT, 7 PMRT), and 10-year rates of LRR with and without PMRT were 4.0% and 7.0%, respectively. Patients receiving PMRT were younger (p = 0.019), had larger tumors (p = 0.0013), higher histologic grade (p = 0.029), more positive LNs (p

Introduction Chemotherapy (CT) is the standard of care for most triple negative breast cancer (TNBC). Chemotherapy is less commonly recommended in older than younger patients. We aim to explore the frequency of CT delivered in elderly patients when compared to young patients. Methods Patients ≤50yrs and ≥70 yrs with stage I-III TNBC defined as ER Results We identified 901 pts with TNBC; 664 (73.7%) were ≤50yrs and 237 (26.3%) were ≥70 yrs. Median followup is 7 yrs (range, 0-16.8yrs). Younger women diagnosed with TNBC were more likely to have stronger family history of breast cancer (p The 5 year rates of DOD were similar between both groups at 10.6% (range, 8.3-13.2) for pts ≤50yrs and 10.8% (range, 7.0-15.4) (p=0.52) for the older group; meanwhile, the 5 year OS rates were significantly different between both groups at 87.5% (range, 84.7-90.0) for pts ≤50yrs and 74.3% (range, 68.2-80.0) (p CT was given to 115 (49%) patients of the ≥70 yrs cohort with a selection biased by larger tumors (p When categorized based on age and receipt of CT, in the 662 pts ≤ 50 yrs, 609 (92%) and 53 (8%) received CT vs no CT respectively; in the 233 pts ≥70 yrs, 115 (49%) and 118 (50%) received CT vs no CT; the cumulative incidence curves for DOD were not statistically different for the four groups (p=0.85) at 5 years. Conclusions In our series, CT was given to 92% of patients ≤ 50 yrs of age. In the elderly pts ≥ 70 yrs of age, CT was limited to 50% of patients, namely those with worse clinicopathologic features. Citation Format: Muhsen S, Dang C, Plitas G, Knezevic A, Stempel M, Patil S, Morrow M, El-Tamer M. Frequency of delivery of systemic chemotherapy in elderly versus younger patients with triple negative breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-13-05.

Introduction Trastuzumab with systemic chemotherapy has shown an improvement in outcomes for patients (pts) with HER2 amplified/overexpressed (HER2+) breast cancer. Pts enrolled onto trials were young with a minority of pts at ≥65 years (yrs) of age. Herein, we report the administration of systemic treatment (ST) (chemotherapy and/or trastuzumab) verus no treatment in elderly pts at a single center. Methods Patients ≥65 yrs with stage I-III HER2+ (defined as IHC 3+ or FISH >2.0) breast cancer, treated at Memorial Sloan Kettering Cancer Center between 2000-2012, were retrospectively identified from our database. Clinicopathologic features were retrieved and co-morbidity indexes (CI) were calculated. Pts were divided by hormone receptor (HR) (defined as ER >10% and/or PR >10%) status into HER2+HR- and HER2+HR+. Each group was further divided by use of ST into: chemotherapy and trastuzumab (CT+T), chemotherapy alone (CT) or no systemic treatment (No Rx). Patients receiving neoadjuvant ST or trastuzumab only as ST were excluded from the KM analysis. Primary objective was to identify patterns of treatment recommendation in the elderly population. We explored disease-free survival (DFS) as estimated using the Kaplan-Meier (KM) method. Results We identified 300 pts ≥65 yrs with HER2+ tumors. 128 (42.7%) were HER2+HR- and 172 (57.3%) were HER2+HR+. The median follow-up for all patients was 6.1 years (range, 0.07-16.7). In the HER2+HR- group, 63 (49.2%) patients received CT+T, 25 (19.5%) CT alone, and 40 (31.3%) had no Rx. Anthracycline based chemotherapy was administered to 57/88 (65%) of patients on CT. Women receiving chemotherapy with or without trastuzumab were younger (65-70 vs >70 years of age) (p=.002) and had more advanced tumor stages (p=.003). Their respective 5-yr DFS KM estimates were 0.84, 0.80, and 0.61 (logrank p=0.06). In the HER2+HR+ group, 77 (44.8%) patients received CT+T, 22 (12.8%) CT alone, and 73 (42.2%) had no Rx. Anthracycline based chemotherapy was administered to 51/99 (51%) of patients on CT. Endocrine therapy was given to 153/172 (89%) of the total cohort. Women receiving chemotherapy with or without trastuzumab were younger (p Conclusions At a single center, in the elderly populations at ≥65 years of age with HER2+ HR- and HER2+HR+ breast cancer, pts who received systemic treatment were younger and had higher stage of disease than those who received no treatment. In an exploratory analysis, there appeared to be a benefit of systemic treatment in pts in the HER+HR- group. Citation Format: Muhsen S, Dang C, Plitas G, Seier K, Stempel M, Patil S, Morrow M, El-Tamer M. Chemotherapy with and without trastuzumab or no treatment in elderly patients with HER2 amplified breast cancer at a single center [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-13-07.

Background The definition of an adequate surgical margin for breast cancer has been a hotly debated topic for over 20 years, with “no ink on tumor” now widely recognized as an adequate pathological margin for invasive carcinoma. Patients with dense breasts pose unique challenges in terms of accurate pre-operative evaluation of extent of disease and achieving adequate margins at initial surgery. The aim of this study therefore is to analyze re-excision rates and correlate with breast density and other clinical and pathological factors before and after the decision to accept 'no tumor at the inked margin” as an adequate margin. Methods Patients with stage I or II invasive breast cancer treated with breast conserving surgery between the 1st of June 2013 and the 31st of October 2014 were included. Patients who had surgery prior to January 1, 2014 comprise the pre-guideline group whereas those who had surgery on or after January 1, 2014 comprise the post-guideline group. Breast density was assessed by 2 independent radiologists. Inter-reader agreement was assessed using data on all study subjects and intra-reader agreement was assessed on a random sample of 121 study subjects; agreement was assessed using the kappa statistic with bootstrap confidence intervals. Logistic regression was used to model the association between breast density and re-excision, using the minimum value of breast density according to the two independent readers, within the 2 time periods. Multivariable logistic regression adjusted for patient and disease characteristics associated with re-excision on univariable analysis. Results The inter-reader agreement was 0.633 (95% confidence interval (CI): 0.604, 0.663) whereas the intra-reader agreement was 0.755 (95% CI: 0.663, 0.834). A total of 1205 patients were included, of whom 504 (41.8%) had surgery before the guideline change and 701 (58.2%) after. Overall 214 (17.8%) had at least one re-excision. The re-excision rate was significantly lower in the time period after the guideline change (15.1% verus 21.4%, p=0.006). There was no significant difference in tumor characteristics between the time periods. Younger age at diagnosis was the only clinicopathological factor that was significantly associated with increased breast density (p Conclusions Women who are of younger age at diagnosis are more likely to have increased breast density. Although, younger age was associated with higher rate of re-excision, we did not find breast density to be associated with a higher rate of re-excision on multivariable analysis. Citation Format: Walsh SM, Brennan SB, Zabor E, Rosenberger LH, Stempel M, Lebron-Zapata L, Gemignani ML. Does breast density increase the risk of re-excision for women with breast cancer having breast conservation therapy? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-12-10.

Neo-adjuvant chemotherapy (NAC) is administered in breast cancer treatment for downstaging of disease. Here, we determined the impact of response to NAC on breast reconstruction uptake. A prospective NAC and mastectomy database with or without reconstruction were reviewed with IRB approval. Univariable analyses were conducted using Kruskal-Wallis or Fisher's exact tests. Multivariable logistic regression was used to adjust for potential confounders. We identified 271 patients with unilateral breast cancer receiving NAC and either unilateral or bilateral mastectomy from 9/2013 to 5/2016. Seventy patients (25.8%) had a pCR to NAC. One hundred and seventy-five patients (64.6%) had immediate reconstruction (IR), and 96 had no IR. On univariable analysis, younger age (P < .001), lower T-stage at presentation (P < .001), bilateral versus unilateral mastectomy (P

Neoadjuvant chemotherapy (NAC) is used to convert patients with inoperable locally advanced breast cancer (LABC) to operability, but has not traditionally been used to avoid mastectomy or axillary dissection in this subset. The purpose of this study was to determine the rates of pathologic complete response (pCR) in LABC patients, and identify factors predictive of pCR to determine if responding patients might be suitable for limited surgery. From 2006 to 2016, 1522 patients received NAC followed by surgery; 321 had advanced disease in the breast (cT4) and/or in the nodes (cN2/N3). pCR rates were assessed by T and N stage, and receptor subtype. Of 321 LABC patients, 223 were cT4, 77 were cN2, and 82 were cN3. Forty-three percent were hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative (HR+/HER2−), 23% were triple negative, and 34% were HER2+. The overall pCR rate was 25% and differed by receptor subtype (HR+/HER2− 7%, triple negative 23%, HER2+ 48%; p

Women with a BRCA mutation have significantly elevated breast cancer risk, which can be reduced by >90% with bilateral prophylactic mastectomy (BPM). We sought to compare a cohort of BRCA mutation carriers choosing BPM versus breast surveillance to better elucidate factors that may impact decision making. Women with a BRCA mutation were retrospectively identified from a prospectively maintained database. The surveillance cohort (n = 313) consisted of women seen in a high-risk clinic between 2014 and 2016, while the surgery cohort (n = 142) consisted of women who underwent BPM between 2010 and 2016. Clinical and familial factors were compared between the groups. Women choosing BPM were more likely to have a BRCA1 than BRCA2 mutation compared with the surveillance group (57 vs. 45%, p = 0.02) and were less likely to have a personal history of ovarian cancer (10 vs. 20%, p = 0.01). Furthermore, women undergoing BPM were more likely to be married (78 vs. 62%, p = 0.01), to have more children (median 2 vs. 1, p

Randomized trials demonstrate equivalent locoregional control with sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) for T1–2 micrometastatic breast cancer, but include few mastectomy patients. Consensus is lacking on indications for post-mastectomy radiotherapy (PMRT) in this population. Herein, we evaluate locoregional recurrence (LRR) in an unselected, modern cohort of T1–2 breast cancer patients with micrometastases or isolated tumor cells (ITCs; N0i+/N1mi) having a mastectomy. We identified patients with T1–2N0i+/N1mi breast cancer treated with mastectomy from January 2006 to December 2011. Recurrent, bilateral, and neoadjuvant cases were excluded. The primary outcome of interest was LRR. Overall, 352 patients [211 (60%) with ITCs and 141 (40%) with micrometastases] were identified. 162 (46%) patients had SLNB alone and one node was positive in 295 (84%) cases; 31 (9%) patients had PMRT and 95% had systemic therapy. At a median 6 years of follow-up, the overall crude LRR rate was 2.8% (n = 9), with no axillary recurrences, and the crude LRR rate was 3.9% among those who had SNB alone. Those with LRR had a median age of 55 years, median tumor size of 1.7 cm, and ductal histology; the majority were high-grade (89%) and estrogen receptor positive (78%), with one positive node (89%). There was no association between LRR and receipt of PMRT (p = 0.4), SLNB versus ALND (p = 0.2), or number of positive nodes (p = 0.7) using the log-rank test. LRR was infrequent among T1–2N0i+/N1mi patients treated with mastectomy without PMRT, with no axillary failures, suggesting that PMRT or nodal radiotherapy are not routinely indicated in this population.

BACKGROUND Indications for postmastectomy radiotherapy (PMRT) in patients with T1 to T2, lymph node-negative (N0) breast cancer with “high-risk” features are controversial. The European Organization for Research and Treatment of Cancer (EORTC) 22922 and National Cancer Institute of Canada Clinical Trials Group MA20 trials reporting improved 10-year disease-free survival with lymph node irradiation included patients with high-risk N0 disease, but, to the authors’ knowledge, benefits in patients receiving modern systemic therapy are uncertain. METHODS The authors retrospectively identified patients with T1 to T2N0 disease who were treated with mastectomy from January 2006 through December 2011. High-risk features included age .05). Receipt of systemic therapy decreased the LRR rate (hazard ratio, 0.40; P = .03). Although crude LRR rates increased from 3.8% to 9.4% with 1 versus ≥ 4 high-risk features, the number of risk factors was not found to be significantly associated with LRR (P = .54). CONCLUSIONS In the current study, a low crude LRR rate (4.7%) was observed in a large unselected cohort of patients with T1 to T2N0 breast cancer with high-risk features who were treated with mastectomy and systemic therapy without PMRT. Although increasing tumor size and the omission of systemic therapy were found to be predictive, other features did not confer a higher LRR risk either independently or together, and do not by themselves mandate the use of PMRT in this patient population. Cancer 2017;123:2626-33. © 2017 American Cancer Society.

PURPOSE: Axillary treatment strategies for the young woman with early-stage, clinically node-negative breast cancer undergoing upfront surgery found to have 1–3 positive sentinel lymph nodes (SLNs) differ significantly after BCT and mastectomy. Here we compare axillary lymph node dissection (ALND) and regional nodal irradiation (NRI) rates between women electing breast-conservation therapy (BCT) versus mastectomy. METHODS: From 2010–2016, women, age

BACKGROUND: Many factors influence decisions regarding choice of breast-conserving surgery (BCS) versus mastectomy with reconstruction for early invasive breast cancer. The purpose of this study was to compare patient satisfaction following BCS and mastectomy with implant reconstruction (M-iR) utilizing the BREAST-Q patient-reported outcome measure. METHODS: Women with stage I or II breast cancer undergoing BCS or M-iR who completed a BREAST-Q from 2010 to 2016 were identified by retrospective review of a prospective database. Baseline characteristics were compared, and linear mixed models were used to analyze associations with BREAST-Q scores over time. RESULTS: Our study group was composed of 3233 women; 2026 (63%) had BCS, 123 (3.8%) had nipple-sparing mastectomy, and 1084 (34%) had skin-sparing or total mastectomy. Median time from surgery to BREAST-Q was 205 days for BCS and 639 days for M-iR (p

The National Comprehensive Cancer Network (NCCN) endorses sentinel lymph node biopsy (SLNB) in patients with clinically positive axillary nodes who downstage after neoadjuvant chemotherapy (NAC). In this study, we compared the accuracy of post-NAC MRI to clinical exam alone in predicting pathologic status of sentinel lymph nodes in cN1 patients. We identified patients with T0-3, N1 breast cancer who underwent NAC and subsequent SLNB from March 2014 to July 2017. Patients were grouped based on whether a post-NAC MRI was done. MRI accuracy in predicting SLN status was assessed versus clinical exam alone. A total of 450 patients met initial study criteria; 269 were analyzed after excluding patients without biopsy-confirmed nodal disease, palpable disease after NAC, and failed SLN mapping. Median age was 49 years. Post-NAC MRI was done in 68% (182/269). Patients undergoing lumpectomy vs mastectomy more frequently received a post-NAC MRI (88 vs 54%, p

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that axillary lymph node dissection (ALND) may be omitted for women with two or fewer positive sentinel nodes (SLNs) undergoing breast-conservation therapy (BCT). Lobular histology comprises a minority of patients, and applicability to these discohesive cancers has been questioned. From August 2010 to March 2017, patients undergoing BCT for cT1-2N0 cancer with positive SLNs were prospectively managed with ALND for three or more positive SLNs or gross extracapsular extension (ECE). In this study, clinicopathologic characteristics and nodal burden were compared between pure/mixed invasive lobular cancer (ILC) and invasive ductal cancer (IDC) patients. Among 813 consecutive patients, 104 (12.8%) had ILC and 709 (87.2%) had IDC. ILC was more often multifocal and low grade, and less frequently had lymphovascular invasion (all p

Background: Indications for post-mastectomy radiotherapy (PMRT) in T1-T2, node negative (N0) breast cancer patients with “high-risk” features are controversial based on lack of consensus as to what constitutes “high-risk”, and variable results of small retrospective studies. The EORTC 22922 and MA20 trials reporting improved 10-year disease-free survival with nodal irradiation included high-risk N0 patients but these patients were not analyzed separately and did not receive modern systemic therapy. We sought to evaluate long-term locoregional control in T1-T2N0 patients with high-risk features undergoing mastectomy in the contemporary era. Methods: We retrospectively identified patients with T1-T2N0 breast cancer with ≥1 high-risk feature treated with mastectomy from 1/2006-12/2011. High-risk features were defined as age Results: Among 672 patients meeting inclusion criteria, 187 (28%) had 1 risk factor: 21 (3%) were age Table 1: Clinicopathologic characteristics, n = 657 Median (Range)Age, years49 (24-89)Tumor size, cm1.4 ( Sentinel node biopsy alone was performed in 98% of these patients. A median of 4 lymph nodes were retrieved (range 1-15). Adjuvant systemic therapy was received by 86% of patients. At median 5.6 years of follow-up, overall LRR rate was 4.7% (n = 31), with the majority (55%) of events involving the chest wall. Increasing tumor size was associated with LRR (HR 1.70, 95% CI 1.26–2.29, p = 0.006), while age, histology, grade, subtype, LVI, multifocality/multicentricity, and tumor location were not (all p > 0.05). Although rate of LRR increased from 3.8% to 9.4% with 1 vs. ≥4 high-risk features, a comparison of 1 vs. 2 vs. 3 vs. ≥4 risk factors was not significant by Kaplan-Meier estimation (p = 0.54). Conclusions: A low LRR rate of 4.7% was seen in this large unselected cohort of T1-T2N0 cancers with "high-risk" features treated by mastectomy and systemic therapy without PMRT. While increasing tumor size was predictive, other features did not confer a higher risk of LRR either independently or together, and do not by themselves mandate the use of PMRT in this population. Citation Format: Mamtani A, Patil S, Stempel M, Morrow M. Are there patients with T1-T2, node-negative breast cancer who are high-risk for locoregional recurrence? [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-13-07.

This study aimed to determine the relationship between mammographic calcifications and magnetic resonance imaging (MRI) tumoral enhancement before and after neoadjuvant chemotherapy (NAC) and to assess the impact of these findings on surgical management. This Institutional Review Board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study involved breast cancer patients who underwent NAC between 2009 and 2015. The study cohort comprised 90 patients with pre- and posttreatment MRI and mammograms demonstrating calcifications within the tumor bed either at presentation or after treatment. The data gathered included pre- and post-NAC imaging findings and post-NAC histopathology, particularly findings associated with calcifications. Comparisons were made using Fisher’s exact test, with p values lower than 0.05 considered significant. Complete resolution of MRI enhancement occurred for 44% of the patients, and a pathologic complete response (pCR) was achieved for 32% of the patients. No statistically significant correlation between changes in mammographic calcifications and MRI enhancement was found (p = 0.12). Resolution of enhancement was strongly correlated with pCR (p < 0.0001). The majority of the patients with pCR demonstrated complete resolution of enhancement (79%, 23/29). No statistically significant relationship was found between changes in calcifications and rates of pCR (p = 0.06). A pCR was achieved most frequently for patients with resolution of enhancement and new, increasing, or unchanged calcifications (p < 0.0001). Although calcifications seen on post-NAC mammography may be associated with benign disease, loss of MRI enhancement does not predict the absence of residual tumor with sufficient accuracy to leave calcifications in place. Complete excision of tumor bed calcifications remains standard practice and a substantial limitation to NAC use for downstaging patients to be eligible for breast conservation treatment.

More than one-third of American adults are obese, and an elevated body mass index (BMI) is postulated to reduce the sensitivity of the clinical evaluation of the axilla. Clinical nodal examination is important in allocating breast cancer patients to appropriate axillary management. This study sought to determine whether BMI influences the rate of nodal positivity in women designated clinically as node-negative (cN0) by physical examination. Breast cancer patients deemed cN0 who underwent sentinel lymph node biopsy (SLNB) from February 2006 to December 2011 were identified from a prospectively maintained database. Clinicopathologic features including BMI and axillary surgery results were recorded and compared among pathologically node-negative and node-positive patients. Overall, 5142 cN0 patients underwent 5262 SLNB procedures during the study period. Nearly one-third of the patients (28 %) were obese (BMI, >30 kg/m2). A positive SLN was identified in 25 % of the patients, and 84 % proceeded to axillary lymph node dissection. Predictors of SLN positivity included younger age, larger tumor size, high nuclear grade, multifocality, and lymphovascular invasion. An increased BMI did not correlate with a higher likelihood of SLN positivity (p = 0.6). The likelihood of cN0 patients having a high burden of axillary metastases (>3 positive nodes) was 4 % overall and, similarly, did not differ according to BMI (p = 0.4). Elevated BMI was not associated with a higher likelihood of SLN positivity or heavy nodal disease burden among women staged as cN0 by physical exam. These findings indicate that physical examination is appropriate and sufficient for preoperative axillary evaluation of women undergoing initial surgery regardless of patient BMI.

The Surgery Versus Active Monitoring for Low-Risk DCIS (LORIS) trial is studying the safety of monitoring core-biopsy diagnosed low-risk ductal carcinoma in situ (DCIS) without excision. We sought to determine the incidence and characteristics of synchronous invasive carcinoma found in LORIS-eligible women who underwent excision, as this knowledge is essential in assessing the safety of observation alone. Women meeting LORIS eligibility criteria (age ≥46 years, screen-detected calcifications, non-high-grade DCIS diagnosed by core biopsy, absence of nipple discharge, or strong family history of breast cancer) who underwent surgical excision from 2009 to 2012 were identified. Histologic findings of excision specimens were reviewed. Overall, 296 LORIS-eligible cases were identified; 58 (20 %) had invasive carcinoma on final pathology (90 % invasive ductal, 78 % >1 mm in size, 21 % high grade, 3 % triple negative, 9 % HER2 amplified). Of these, 18 (31 %) were pT1b or larger and 3 (5 %) were pN1. Among eligible upgraded cases, 90 % received radiation, 89 % received endocrine therapy, and 18 % were recommended chemotherapy. Women upgraded to invasive carcinoma were more likely to have intermediate-grade DCIS on core biopsy and to have undergone mastectomy. Among LORIS-eligible women, 20 % had invasive carcinoma at surgical excision that was heterogeneous in grade, size, and receptor status. Information gained from surgical excision influenced receipt of adjuvant radiation and endocrine therapy in most patients, and indicated benefit from chemotherapy in 18 % of patients. Surgical excision is warranted until additional risk stratification is available to identify a cohort of DCIS patients at lower risk for clinically significant synchronous invasive carcinoma.

BACKGROUND Black women with breast cancer have lower survival rates and higher recurrence rates in comparison with white women. This study compared treatment and survival outcomes for black and white women at a highly specialized tertiary care cancer center. METHODS An institutional review board-approved, retrospective institutional database review was performed to identify all black women treated for invasive breast cancer between 2005 and 2010. Women with a prior history of breast cancer, stage IV cancer, or bilateral breast cancer were excluded. White women had similar exclusion criteria applied and were then matched to black women 1:1 by age and diagnosis year. Clinicopathologic and treatment variables were compared by race. Kaplan-Meier methodology was used to estimate overall survival (OS) and disease-free survival (DFS); a multivariable analysis was conducted with Cox regression models. RESULTS The study group consisted of 1332 women (666 black). The median tumor size was larger in black women (1.6 vs 1.3 cm; P

BACKGROUND/OBJECTIVE. Recent prospective trials support the use of sentinel lymph node biopsy (SLNB) in breast cancer patients after neoadjuvant chemotherapy (NAC) with a lower false negative rate if three or more sentinel lymph nodes (SLNs) are identified. In this study, we investigated whether the pre-NAC axillary lymph node status influences the number of SLNs identified. METHODS. Stage I–III breast cancer patients who received NAC and underwent SLNB from May 2014 to April 2016 were identified from an institutional prospective database. Clinical and pathological factors among clinically node-negative (cN−) and clinically node-positive (cN+) patients who converted to cN− post-NAC were compared. Generalized linear mixed models analyzed factors associated with the number of SLNs removed. RESULTS. Among 343 patients who underwent SLNB during the study period, 335 (98%) had at least one SLN identified, and subsequently comprised the study population. The median number of SLNs identified was 4 (range 1–14), which did not differ according to pre-NAC nodal status (p = 0.15). Overall, 85% of patients had three or more SLNs identified (80% cN− group vs. 89% cN+ group; p = 0.02). On univariable analysis, age

Both patients with inflammatory breast cancer (IFLBC) and patients with noninflammatory T4 breast cancer (non-IFLBC) have a heavy disease burden in the breast; whether the unique biology of IFLBC conveys a higher locoregional recurrence (LRR) risk and worse outcomes in comparison with other T4 lesions is uncertain. Here the outcomes of patients with IFLBC and patients with non-IFLBC treated with modern multimodality therapy are compared.Patients with nonmetastatic T4 breast cancer treated with neoadjuvant chemotherapy, mastectomy, and radiation therapy between 2006 and 2016 were identified. Recurrences and survival were compared between patients with IFLBC and patients with non-IFLBC overall and stratified by receptor subtype.For 199 T4 patients, the median age was 52 years, and the median clinical tumor size was 7 cm. One hundred seventeen (59%) had IFLBC. With a median follow-up of 41 months, 4 patients had isolated LRR; all cases occurred in patients with IFLBC. The 5-year isolated LRR rate for patients with IFLBC was 4.8%. Overall, 14 patients had both LRR and distant recurrence (DR); 47 had DR only. The 5-year distant recurrence-free survival (DRFS) rates were similar for patients with IFLBC and patients with non-IFLBC (63% vs 71%; log-rank P = .14). The 5-year DRFS rate was lowest among triple-negative (TN) patients (43%) and was significantly lower for patients with TN IFLBC versus patients with non-IFLBC (28% vs 62%; log-rank P = .02). The 5-year overall survival rates (71% vs 74%; log-rank P = .4) and cancer-specific survival rates (74% vs 79%; log-rank P = .23) did not differ between IFLBC and non-IFLBC.Although IFLBC is often considered a unique biologic subtype, patients with IFLBC and patients with non-IFLBC had similar outcomes with modern multimodality therapy; isolated LRR was uncommon. The TN subtype in patients with IFLBC is associated with poor outcomes, and this indicates the need for new treatment approaches in this group.

Reoperative sentinel lymph node biopsy (SLNB) is feasible in patients with local recurrence (LR) of invasive breast cancer but it remains unclear if this procedure affects either treatment or outcome. In this study, we ask whether axillary restaging (vs. none) at the time of LR affects the rate of subsequent events: axillary failure (AF), non-axillary recurrence (NAR), distant metastasis, or death. We queried our institutional database to identify patients treated surgically for invasive breast cancer with a negative SLNB (1997–2000) who developed ipsilateral breast or chest wall recurrence as a first event. We excluded those with gross nodal disease at the time of LR. The cumulative incidence of subsequent events was estimated using competing risks methodology. Of 1527 patients with negative SLN at initial surgery, 83 had an ipsilateral breast (79) or chest wall recurrence (4) with clinically negative regional nodes; 47 (57 %) were treated with and 36 (43 %) without axillary surgery. Primary tumor characteristics were similar between groups, although time to LR was shorter in the no axillary surgery group (median 3.4 vs. 6.5 years; p

Background Nipple-sparing mastectomy (NSM) is associated with improved cosmesis and is being performed increasingly. Its role in BRCA mutation carriers has not been well described. This was a study of the indications for, and outcomes of, NSM in BRCA mutation carriers. Methods BRCA mutation carriers who underwent NSM were identified. Details of patient demographics, surgical procedures, complications, and relevant disease stage and follow-up were recorded. Results A total of 177 NSMs were performed in 89 BRCA mutation carriers between September 2005 and December 2013. Twenty-six patients of median age 41 years had NSM for early-stage breast cancer and a contralateral prophylactic mastectomy. Mean tumour size was 1·4 (range 0·1–3·5) cm. Sixty-three patients of median age 39 years had prophylactic NSM, eight of whom had an incidental diagnosis of ductal carcinoma in situ. There were no local or regional recurrences in the 26 patients with breast cancer at a median follow-up of 28 (i.q.r. 15–43) months. There were no newly diagnosed breast cancers in the 63 patients undergoing prophylactic NSM at a median follow-up of 26 (11–42) months. All patients had immediate breast reconstruction. Five patients (6 per cent) required subsequent excision of the nipple–areola complex for oncological or other reasons. Skin desquamation occurred in 68 (38·4 per cent) of the 177 breasts, and most resolved without intervention. Debridement was required in 13 (7·3 per cent) of the 177 breasts, and tissue-expander or implant removal was necessary in six instances (3·4 per cent). Conclusion NSM is an acceptable choice for patients with BRCA mutations, with no evidence of compromise to oncological safety at short-term follow-up. Complication rates were acceptable, and subsequent excision of the nipple–areola complex was rarely required.

Bilateral breast cancer (BBC) may present as synchronous (SBC) or metachronous breast cancer (MBC). Optimal surgical management of BBC patients is not well-defined. In this study, we report on histopathology, treatment, and outcomes in BBC patients. Upon Institutional Review Board approval, we identified BBC patients diagnosed and treated for invasive breast cancer between 1999 and 2007. Retrospective chart review for demographics, histopathology, treatment, and outcomes was performed, and factors associated with BCS choice were collected. Contraindication to BCS was defined as any of the following one-breast findings: multicentric disease, tumor considered too large for BCS, and a patient without a nominal breast size for acceptable cosmetic results. McNemar’s test for matched pairs (binary variables) or the paired t test (continuous variables) were used to examine if a pathologic characteristic differed within a cancer pair. Kaplan–Meier methods estimated overall survival (OS). A total of 203 BBC patients (119 SBC, 84 MBC) comprised our study group. Histopathologic characteristics of the first and second cancers diagnosed in both the SBC and MBC patients were very similar in histologic type and molecular profiles. Overall, 57 % of MBC patients underwent breast-conserving surgery (BCS) at initial diagnosis versus 34 % of patients with SBC. BCS contraindications were similar in both groups: 16 (34 %) MBC patients and 28 (36 %) SBC patients. Kaplan–Meier OS estimates at 5 and 10 years were 86 and 78 % for MBC, and 87 and 77 % for SBC patients, respectively. OS was excellent for both the MBC and SBC groups. Contraindications to BCS did not differ between groups. However, patients with SBC were less likely to undergo BCS compared with patients with MBC at the time of initial diagnosis.

Introduction: Nipple sparing mastectomy (NSM) is now performed with increasing frequency in both therapeutic and prophylactic breast surgery. The role of NSM in BRCA1 and BRCA2 mutation carriers has not been well described. The aim of this study was to review our experience with NSM in this high-risk population. Methods: A review of the breast database was performed to identify all patients with documented BRCA mutations who underwent NSM at Memorial Sloan Kettering Cancer Center. Data extracted from the database included patient demographics, type of mutation, indication for surgery, type of reconstruction, and complications. For patients undergoing therapeutic mastectomy, data on disease stage, axillary procedures, and follow-up were also extracted. Results: 177 NSMs (88 bilateral, 1 unilateral) were performed in 89 female patients with a documented BRCA mutation between September 2005 and December 2013. There were 56 patients with BRCA1 mutation, 26 with BRCA2 mutation, and 7 with genetic variants of uncertain significance. 26 patients had a therapeutic NSM for breast cancer (stage 0: n=6; stage 1: n=15; stage 2: n=5) and concurrent contralateral prophylactic mastectomy (CPM). The mean tumor size was 1.46cm (range, 0.1-3.5cm), and all were node negative following sentinel lymph node biopsy. 63 patients had NSM for prophylaxis. The mean age of patients undergoing therapeutic NSM was 41 years (range, 26-59) and prophylactic NSM was 39 years (25-59). There was an incidental diagnosis of ductal carcinoma in situ (DCIS) in 4 women undergoing CPM and 4 patients undergoing prophylactic NSM, including 1 patient diagnosed with bilateral DCIS, and an incidental diagnosis of atypia in 8 patients undergoing prophylactic NSM. In 26 patients undergoing therapeutic NSM, at median follow-up of 2.34 years (range, 0.45-6.06) there were no local or regional recurrences. One patient developed distant metastases and subsequently died from her disease, and 1 other patient died from metastatic ovarian cancer. In 63 patients undergoing prophylactic NSM, at median follow-up of 2.15 years (range, 0.11-8.14) there were no newly diagnosed breast cancers or deaths. Following NSM, 5 patients (5.6%) required subsequent excision of the nipple-areolar complex (3 cases for close or positive DCIS on final histology, 1 case for infection with necrosis, and 1 case for ongoing nipple discharge). All 89 patients had immediate breast reconstruction (tissue expander: n=80; permanent implant: n=8; autologous (DIEP) flap: n=1). Postoperative complications are shown in Table 1. Postoperative complications following 177 nipple sparing mastectomies performed in 89 patients with BRCA mutations No. of Breasts; n (%)No. of Patients; n (%)Skin desquamation68 (38.4)40 (44.9)Necrosis requiring debridement18 (10.2)13 (14.6)Infection7 (4.0)7 (7.9)Hematoma3 (1.69)3 (3.4)Complication requiring implant or tissue expander removal6 (3.4)6 (6.7) Conclusion: NSM is an acceptable choice for patients with BRCA gene mutations undergoing therapeutic or prophylactic mastectomy with no evidence of compromise to oncological safety. This report shows an acceptable complication rate, and patients rarely required subsequent excision of the nipple-areolar complex. Citation Format: Aidan T Manning, Andrea Pusic, Caitlin Wood, Anne Eaton, Michelle Stempel, Deborah Capko, Virgilio Sacchini. Nipple sparing mastectomy in patients with BRCA1 and BRCA2 mutations [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-13-02.

Strategies to reduce the likelihood of axillary lymph node dissection (ALND) include application of Z0011 or use of neoadjuvant chemotherapy (NAC). Indications for ALND differ by treatment plan, and nodal pathologic complete response rates after NAC vary by tumor subtype. This study compared ALND rates for cT1-2N0 tumors treated with upfront surgery versus those treated with NAC. The ALND rates for cT1-2N0 breast cancer patients were compared by tumor subtype among women undergoing upfront surgery to NAC. Multivariable analysis with control for age, cT stage, and lymphovascular invasion, and stratification by subtype was performed. The study identified 1944 cancers in 1907 women who underwent sentinel lymph node (SLN) biopsy with or without ALND (669 upfront breast-conserving surgeries [BCSs], 1004 upfront mastectomies, 271 NACs). Compared with the NAC group, the ALND rates in the BCS group were lower for estrogen receptor (ER), progesterone receptor-positive (PR+), human epidermal growth factor 2-negative (HER2−) tumors (15 vs 34%; p

The benefit of neoadjuvant chemotherapy (NAC) in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancers and in invasive lobular carcinoma (ILC) is uncertain due to the low rates of pathologic complete response (pCR). The aim of this study was to determine if pathologic features can identify subsets likely to benefit from NAC. Patients with stage I–III ER+, HER2− breast cancer receiving NAC were retrospectively reviewed. Endpoints were downstaging to breast-conserving surgery (BCS) and nodal pCR after NAC. Patients were grouped by progesterone receptor (PR) status and grade/differentiation (high grade or poor [HP] vs. non-HP). From 2007 to 2016, 402 ER+/HER2− cancers in patients receiving NAC were identified. Median age was 50 years, 98% were clinical stage II–III, and 75% were cN+. Overall pCR rate was 5%; breast pCR in 7% and nodal pCR in 15% of cN+ patients (p

Observational data suggest that metformin use decreases breast cancer (BC) incidence in women with diabetes; the impact of metformin on BC outcomes in this population is less clear. The purpose of this analysis was to explore whether metformin use influences BC outcomes in women with type 2 diabetes. Prospective institutional databases were reviewed to identify patients with diabetes who received chemotherapy for stages I–III BC from 2000 to 2005. Patients diagnosed with diabetes before or within 6 months of BC diagnosis were included. Males and those with type I, gestational, or steroid-induced diabetes were excluded. Patients were stratified based on metformin use, at baseline, defined as use at time of BC diagnosis or at diabetes diagnosis if within 6 months of BC diagnosis. Kaplan–Meier methods were used to estimate rates of recurrence-free survival (RFS), overall survival (OS), and contralateral breast cancer (CBC). We identified 313 patients with diabetes who received chemotherapy for BC, 141 (45%) fulfilled inclusion criteria and 76 (54%) used metformin at baseline. There were no differences in clinical presentation or tumor characteristics between metformin users and nonusers. At a median follow-up of 87 months (range, 6.9–140.4 months), there was no difference in RFS (P = 0.61), OS (P = 0.462), or CBC (P = 0.156) based on metformin use. Five-year RFS was 90.4% (95% CI, 84–97) in metformin users and 85.4% (95% CI, 78–94) in nonusers. In this cohort of patients with type 2 diabetes receiving systemic chemotherapy for invasive BC, the use of metformin was not associated with improved outcomes.

Whether extracapsular extension (ECE) of tumor in the sentinel lymph node (SLN) is an indication for axillary lymph node dissection (ALND) in patients managed by American College of Surgeons Oncology Group Z0011 criteria is controversial. Here we examine the correlation between ECE in the SLN and disease burden in the axilla.Patients meeting Z0011 clinicopathologic criteria (pT1-2, cN0 with3 positive SLNs) were selected from a prospectively maintained database (2006-2013). Chart review documented the presence and extent of ECE. Neoadjuvant chemotherapy patients were excluded. Comparisons were made by presence and extent (≤2 vs.2 mm) of ECE.Of 11,730 patients, 778 were pT1-2, cN0 with3 positive SLNs without ECE, and 331 (2.8 %) had ECE. Of these, 180 had ≤2 mm and 151 had2 mm of ECE. Patients with ECE were older (57 vs. 54 years; p = 0.001) and had larger (2.0 vs. 1.7 cm; p0.0001), multifocal (p = 0.006), hormone receptor-positive tumors (p = 0.0164) with lymphovascular invasion (p0.0001). Presence and extent of ECE were associated with greater axillary disease burden; 20 and 3 % of patients with and without ECE, respectively, had ≥4 additional positive nodes at completion ALND (p0.0001), and 33 % of patients with2 mm ECE had ≥4 additional positive nodes at completion ALND, compared with 9 % in the2 mm group (p0.0001). On multivariate analysis,2 mm of ECE was the strongest predictor of ≥4 positive nodes at completion ALND (odds ratio 14.2).Presence and extent of ECE were significantly correlated with nodal tumor burden at completion ALND, thus suggesting that2 mm of ECE may be an indication for ALND or radiotherapy when applying Z0011 criteria to patients with metastases in3 SLNs. ECE reporting should be standardized to facilitate future studies.

Postmastectomy radiation (PMRT) in T1–T2 tumors with 1–3 positive axillary lymph nodes (ALNs) is controversial. Impact of molecular subtype (MST) on locoregional recurrence (LRR) and PMRT benefit is uncertain. We examined the association between MST and LRR, recurrence-free survival (RFS), and overall survival (OS), in T1–T2 tumors with 1–3 positive ALNs. From an institutional database, we identified mastectomy patients with 1–3 positive ALNs between 1995 and 2006. Patients who received neoadjuvant chemotherapy, had T3–T4 tumors, or ≥4 positive ALNs were excluded. MST was defined as: hormone receptor (HR)+/HER2−(luminal A/B), HR+/HER2+(luminal HER2), HR−/HER2+(HER2), and HR−/HER2−(basal). Kaplan–Meier method and Cox regression analysis were used to examine association between MST and LRR, RFS, and OS. This study included 884 patients (700 no PMRT, 141 PMRT): 72.8 % luminal A/B, 7.8 % luminal HER2, 6.8 % HER2, and 12.6 % basal. Median follow-up was 6.3 years; 39 LRRs occurred. Luminal A/B subtype had the smallest tumors (p = 0.03), lowest intraductal component (p = 0.01), histologic grade (p

The effect of increasing negative margin width after breast-conserving therapy (BCT) on local recurrence (LR) is controversial. LR rates vary by subtype, with the highest rates seen in triple-negative breast cancer (TNBC). This study examined LR rates in relationship to margin width in TNBC treated with BCT.Women with TNBC who underwent BCT between 1999 and 2009 were identified. Margins were defined as positive (ink on tumor), 0.1-2.0, and 2 mm. Patients with positive margins were excluded. Statistical comparisons were by t test, Fisher's exact test, and Wilcoxon rank sum test. Cumulative incidence of LR was compared by competing-risks methodology.Of 535 cancers, 71 had margins ≤2 mm and 464 had margins2 mm. At a median follow-up of 84 months (range 8-165 months), there were 37 local, 18 regional, and 77 distant recurrences or deaths as first events. Ten patients had a locoregional recurrence before planned radiotherapy and were excluded from cumulative incidence analyses. The cumulative incidence of LR at 60 months for margins ≤2 mm was 4.7 % (95 % confidence interval 0-10.0) and for2 mm was 3.7 % (1.8, 5.5) (p = 0.11). After controlling for chemotherapy and tumor size, there was no difference in LR between the two margin groups (p = 0.06). A difference in the risk of distant recurrence or death was not observed (p = 0.53).Margin width of2 mm was not associated with reduced LR rates. These data support a negative margin definition of no ink on tumor, even in this high-risk TNBC cohort.

Postmastectomy radiotherapy (PMRT) is well established in patients with ≥4 positive axillary lymph nodes (ALN); indications in 1 to 3 positive ALN remains controversial. We examined clinicopathologic criteria used for PMRT selection and compared locoregional recurrence (LRR), recurrence-free survival (RFS), and overall survival (OS) among patients with and without PMRT.Between 1995 and 2006, a total of 1,331 patients with T1-T2 tumors and 1 to 3 positive ALN underwent mastectomy. We excluded T3/T4 tumors and neoadjuvant chemotherapy; we analyzed 1,087 patients (924 without PMRT, 163 with PMRT). Chi square testing compared clinicopathologic features between groups. The Kaplan-Meier method and Cox regression analysis examined the association between PMRT and LRR, RFS, and OS.PMRT patients were more likely to be ≤50 years old (p = 0.001) and to have larger tumors (p = 0.01), disease of a higher histologic grade (p = 0.03), lymphovascular invasion (LVI) (p0.0001), a greater number of positive ALN (p0.0001), extranodal invasion (p0.0001), and macroscopic ALN metastases (p0.0001). With a median follow-up of 7 years, PMRT and no-PMRT groups were similar in LRR (p = 0.57), RFS (p = 0.70), and OS (p = 0.28). On multivariate analysis of the no-PMRT group, age ≤50 years (p = 0.002) and presence of LVI (p0.0001) were associated with LRR. Stratified by age and LVI, patients ≤50 years old and with LVI had the highest 5-year LRR, 10.1 versus 1.1 %, than in patients50 years old without LVI (p0.001).By using clinicopathologic features, clinicians delivered PMRT to a select group of patients with T1-T2 tumors and 1 to 3 positive ALN, resulting in similarly low rates of 5-year LRR. Among patients not receiving PMRT, age ≤50 years and LVI were associated with increased LRR rates and warrant PMRT consideration.

Wire localization (WL) of nonpalpable breast cancers on the day of surgery is uncomfortable for patients and impacts operating room efficiency. Radioactive seed localization (RSL) before the day of surgery avoids these disadvantages. In this study we compare outcomes of our initial 6-month experience with RSL to those with WL in the preceding 6 months.Lumpectomies for invasive or intraductal cancers localized with a single (125)iodine seed (January-June 2012) were compared with those using 1 wire (July-December 2011). Surgeons and radiologists did not change. Positive and close margins were defined as tumor on ink and tumor ≤1 mm from ink, respectively. Demographic and clinical characteristics and outcomes were compared between RSL and WL patients.There were 431 RSL and 256 WL lumpectomies performed. Clinicopathologic characteristics did not differ between groups. Most seeds (90 %) were placed before the day of surgery. Positive margins were present in 7.7 % of RSL versus 5.5 % of WL patients, and 16.9 % of RSL versus 19.9 % of WL had close margins (p = 0.38). The median operative time was longer for lumpectomy and sentinel lymph node biopsy (SLNB) in the RSL group (55 vs. 48 min, p0.0001). There was no significant difference in the volume of tissue excised between groups.In the first 6 months of RSL, operative scheduling was simplified, while rates of positive and close margins were similar to those seen after many years of experience with WL. Operative time was slightly longer for RSL lumpectomy and SLNB; we anticipate this will decrease with experience.

The National Comprehensive Cancer Network guidelines recommend axillary imaging prior to neoadjuvant chemotherapy (NAC) in breast cancer patients who are clinically node negative (cN0) by physical examination. However, the benefit of this approach remains uncertain. The purpose of this study was to determine whether abnormal axillary imaging pre-NAC predicts nodal metastases post-NAC (ypN+) in cN0 patients. cN0 patients undergoing NAC followed by axillary surgery were identified. Rates of ypN+ were compared among patients with abnormal pre-treatment axillary imaging vs. normal or no pre-treatment imaging using Fisher’s exact test. From May 2008 to March 2016, 402 eligible cN0 patients were identified. The median age of the patients was 49.5 years, and the median tumor size was 4 cm. Of these patients, 38% were estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2−), 30% were HER2+ , and 32% were triple negative. All had pre-NAC mammograms, 40% axillary ultrasound, 83% MRI, and 51% PET. Abnormal nodes on imaging were seen in 208 patients (52%); 128 had pre-NAC node biopsy, and 75 were positive. Overall, 28% of the patients (n = 111) were ypN+ post-NAC. Although the incidence of ypN+ was significantly higher in patients with abnormal nodes on pre-NAC imaging (p = 0.001), 54% did not require axillary lymph node dissection (ALND) post-NAC. Among the patients with normal nodes on pre-NAC imaging, 20% were ypN+ post-NAC. Half of patients with abnormal nodes on pre-NAC imaging did not require ALND post-NAC, while 20% of those with normal pre-NAC nodes had disease post-NAC, indicating that in cN0 patients already selected for NAC, axillary imaging pre-NAC does not predict the need for axillary surgery post-NAC with sufficient accuracy to be clinically useful.

OncotypeDX, a multi-gene expression assay, has been incorporated into clinical practice as a prognostic and predictive tool. However, its use in resource-constrained international healthcare systems is limited. Here we develop and validate a simplified model using clinicopathologic criteria to predict OncotypeDX score.Patients with estrogen receptor (ER) and/or progesterone receptor (PR)-positive and HER2-negative invasive ductal carcinoma for whom the OncotypeDX test was successfully performed between 09/2008 and 12/2011 were retrospectively identified. Tumor size, nuclear and histologic grade, lymphovascular invasion, and ER and PR status were extracted from pathology reports. Data were split into a training dataset comprising women tested 09/2008-04/2011, and a validation dataset comprising women tested 04/2011-12/2011. Using the training dataset, linear regression analysis was used to identify factors associated with OncotypeDX score, and to create a simplified risk score and identify risk cutoffs.Estrogen and progesterone receptors, tumor size, nuclear and histologic grades, and lymphovascular involvement were independently associated with OncotypeDX. The full model explained 39% of the variation in the test data, and the simplified risk score and cutoffs assigned 57% of patients in the test data to the correct risk category (OncotypeDX score 18, 18-30,30). 41% of patients were predicted to have OncotypeDX score 18, of these 83, 16, and 2% had true scores of 18, 18-30, and 30, respectively.Awaiting an inexpensive test that is prognostic and predictive, our simplified tool allows clinicians to identify a fairly large group of patients (41%) with very low chance of having high-risk disease (2%).

Triple-negative breast cancer (TNBC) subtype and young patient age are both associated with an increased risk of local recurrence (LR) and distant recurrence (DR). In young women with TNBC, it is unclear whether subtype or patient age is driving prognosis. Patients treated for primary TNBC from 1998 to 2011 were identified from the breast surgery database. Clinicopathologic characteristics, treatment, and outcomes were compared between patients

False-negative rates (FNR) of sentinel node biopsy (SNB) after neoadjuvant chemotherapy (NAC) in node-positive (N+) breast cancer patients are10 % when ≥3 negative SNs are obtained. Marking positive nodes has been suggested to reduce FNR. Identification of treatment effect in the nodes post-NAC is an alternative to decrease FNR. We evaluated the frequency of treatment effect in N+ patients after a pathologic complete response (pCR) with NAC.Biopsy-proven N+ patients receiving NAC were identified. Patients with nodal pCR after axillary lymph node dissection (ALND) or SNB with dual mapping and ≥3 SNs removed were evaluated for treatment effect; ALND and SNB patients were compared.From January 2009 to December 2015, 528 N+ patients received NAC. Of these, 204 had a nodal pCR, 135 had an ALND, and 69 had SNB. Median age was 49 years, 15 % were hormone receptor positive (HR+)/HER2-, 27 % triple negative, and 58 % HER2+. The median number of nodes removed in ALND patients was 17 versus 4 in SNB patients. Treatment effect in nodes was identified in 192 patients (94 %) and was more common in ALND versus SNB patients (97 vs 88 %; p = .02). HR+ patients and patients without a breast pCR were less likely to have treatment effect in the nodes (p = .05). Other characteristics did not differ.Following NAC, SNs with treatment effect were retrieved in 88 % of patients without marking nodes, suggesting that nodal clipping may not be necessary to achieve an acceptable FNR. Longer follow-up is needed to determine regional recurrence rates in the SN-only cohort.

Reexcision rates in patients undergoing breast-conserving surgery (BCS) for early-stage invasive breast cancer are highly variable. The Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) published consensus guidelines to help standardize practice. We sought to determine reexcision rates before and after guideline adoption at our institution. We identified patients with stage I or II invasive breast cancer initially treated with BCS between June 1, 2013, and October 31, 2014. Margins were defined as positive (tumor on ink), close (≤1 mm), or negative (>1 mm), and were recorded for both invasive cancer and ductal carcinoma-in situ (DCIS) components. Reexcision rates were quantified, characteristics were compared between groups, and multivariable logistic regression was performed. A total of 1205 patients were identified, 504 before and 701 after the guideline adoption (January 1, 2014). Clinical and pathologic characteristics were similar between time periods. Reexcision rates significantly declined from 21.4 to 15.1 % (p = 0.006) after guideline adoption. A multivariable model identified extensive intraductal component (odds ratio [OR] 2.5, 95 % confidence interval [CI] 1.2–5.2), multifocality (OR 2.0, 95 % CI 1.2–3.6), positive (OR 844.4, 95 % CI 226.3–5562.5) and close (OR 38.3, 95 % CI 21.5–71.8) ductal carcinoma-in situ margin, positive (OR 174.2, 95 % CI 66.2–530.0) and close (OR 6.4, 95 % CI 3.0–13.6) invasive margin, and time period (OR 0.5, 95 % CI 0.3–0.9 for post vs. pre) as independently associated with reexcision. Overall reexcision rates declined significantly after guideline adoption. Close invasive margins were associated with higher rates of reexcision than negative invasive margins in both time periods; however, the effect diminished in the postguideline adoption period. Thus, we expect continued decline in reexcision rates as adherence to guidelines becomes more uniform.

This study was designed to determine the incidence of late axillary recurrence (AR) in patients with negative sentinel lymph node biopsy (SLNB) and provide a comparison with SLNB positive patients who underwent axillary lymph node dissection (ALND). Retrospective analysis of prospectively collected data on all breast cancer patients with negative SLNB from January 1997 to December 2000 was performed on a large, institutional database. Primary outcome was cumulative incidence of AR as a first event with/without concurrent local recurrence. SLNB positive patients who went on to ALND during the same timeframe were comparatively analyzed. A total of 1529 eligible patients were identified (median age 58 years, median tumor size 1.0 cm): 1297 (85 %) underwent lumpectomy; 1099 (75 %) received adjuvant radiation; and 874 (80 %) were estrogen receptor-positive. At 10.8 (range 0–16) years median follow-up, overall incidence of AR as a first event was low (n = 13). Cumulative incidence was 0.6 % [95 % confidence interval (CI) 0.2–0.9] 5 years after SLNB, and 0.9 % (95 % CI 0.4–1.4, 95 % CI 0.5–1.6) at 10 and 15 years. Late AR (>5 years after surgery) occurred in five patients. Median overall survival after AR was 4.6 years; median distant disease-free survival after AR was 3.8 years. Late AR was also low in a contemporaneous group of SLNB positive patients undergoing ALND. In this group, cumulative incidence of AR was 0.7 % (95 % CI 0.1–1.3) 5 years after surgery, and 0.8 % (95 % CI 0.2–1.5) at 10 and 15 years. Late AR after negative SLNB is rare; the majority of ARs are in the first 5 years after surgery. Prognosis after these events is poor. SLNB remains a safe and effective procedure for axillary evaluation in breast cancer.