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The aims of the Oncoplastic Breast Consortium initiative were to identify important knowledge gaps in the field of oncoplastic breast-conserving surgery and nipple-sparing or skin-sparing mastectomy with immediate breast reconstruction, and to recommend appropriate research strategies to address these gaps. A total of 212 surgeons and 26 patient advocates from 55 countries prioritised the 15 most important knowledge gaps from a list of 38 in two electronic Delphi rounds. An interdisciplinary panel of the Oncoplastic Breast Consortium consisting of 63 stakeholders from 20 countries obtained consensus during an in-person meeting to select seven of these 15 knowledge gaps as research priorities. Three key recommendations emerged from the meeting. First, the effect of oncoplastic breast-conserving surgery on quality of life and the optimal type and timing of reconstruction after nipple-sparing or skin-sparing mastectomy with planned radiotherapy should be addressed by prospective cohort studies at an international level. Second, the role of adjunctive mesh and the positioning of implants during implant-based breast reconstruction should ideally be investigated by randomised controlled trials of pragmatic design. Finally, the BREAST-Q questionnaire is a suitable tool to assess primary outcomes in these studies, but other metrics to measure patient-reported outcomes should be systematically evaluated and quality indicators of surgical morbidity should be further assessed.

Objective This study sought to estimate the incidence and incidence rate of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) at a high-volume single institution, which enables vigorous long-term follow-up and implant tracking for more accurate estimates. Summary background data The reported incidence of BIA-ALCL is highly variable, ranging from 1 in 355 to 1 in 30,000 patients, demonstrating a need for more accurate estimates. Methods All patients who underwent implant-based breast reconstruction from 1991 to 2017 were retrospectively identified. The incidence and incidence rate of BIA-ALCL were estimated per patient and per implant. A time-to-event analysis was performed using the Kaplan-Meier estimator and life table. Results During the 26-year study period, 9373 patients underwent reconstruction with 16,065 implants, of which 9589 (59.7%) were textured. Eleven patients were diagnosed with BIA-ALCL, all of whom had a history of textured implants. The overall incidence of BIA-ALCL was 1.79 per 1000 patients (1 in 559) with textured implants and 1.15 per 1000 textured implants (1 in 871), with a median time to diagnosis of 10.3 years (range, 6.4-15.5 yrs). Time-to-event analysis demonstrated a BIA-ALCL cumulative incidence of 0 at up to 6 years, increasing to 4.4 per 1000 patients at 10 to 12 years and 9.4 per 1000 patients at 14 to 16 years, although a sensitivity analysis showed loss to follow-up may have skewed these estimates. Conclusions BIA-ALCL incidence and incidence rates may be higher than previous epidemiological estimates, with incidence increasing over time, particularly in patients exposed to textured implants for longer than 10 years.

Opioid analgesics are overprescribed after surgery. In August 2018, the authors replaced routine discharge opioid prescription with a nonsteroidal anti-inflammatory drug (NSAID) for patients who had a lumpectomy or excisional biopsy (lump/ex). This study compared patient-reported post-discharge pain scores for patients treated before and after the change in routine discharge medication. Patients were categorized based on treatment before and after a change in discharge medication as follows: study period 1 (routine opioids), study period 2 (routine NSAID). Pain severity was assessed with an electronic survey on postoperative days (PODs) 1 to 5. Multivariable generalized estimating equations tested the association between pain severity and discharge in the first versus the second study period. Lump/ex was performed for 1606 patients between December 2017 and June 2019. Of these patients, 789 (49%) reported pain scores and were analyzed (328 in study period 1, 461 in study period 2). Opioid prescription at discharge decreased from 96% in period 1 to 14% (95% confidence interval [CI], 11–18%) in period 2. Only 1% of the patients discharged with NSAID were later prescribed an opioid. The maximum reported pain score on any POD for all the patients was severe for 30 patients (3.8%), moderate for 217 patients (28%), mild for 430 patients (54%), and none for 112 patients (14%). The estimated risk for moderate or greater pain on POD 1 was 36% for period 1 and 34% for period 2. The proportion of patients reporting moderate or greater pain was nonsignificantly lower for the patients treated in period 2 (odds ratio [OR], 0.91; 95% CI 0.67–1.22; P = 0.5). For patients undergoing lump/ex, a clinically meaningful difference in reported post-discharge pain scores can be excluded with a change to routine NSAID at discharge. Patients undergoing lump/ex should not be routinely discharged with opioids.

Postmastectomy radiation (PMRT) and regional nodal irradiation (RNI) improve outcomes for patients at high risk of locoregional recurrence (LRR). Node-negative patients with the triple-negative (TN) subtype and those who do not have a pCR with neoadjuvant chemotherapy (NAC) are at increased risk for LRR, but whether the absolute risk for LRR is high enough to justify PMRT/RNI is uncertain. Patients with cT1-T3N0 and pN0 disease treated with NAC who had residual disease in the breast were identified from a prospective database. Patients were eligible for the study if they had mastectomy or breast-conserving therapy with negative margins and whole-breast radiation. Those receiving PMRT or RNI were excluded. Actuarial rates were estimated using the cumulative incidence function. The 227 patients in this study had a mean age was 51.4 ± 12.6 years, and 82 (36.1%) were TN. During a median follow-up period of 35 months, nine LRR events occurred. The overall crude and actuarial 3-year LRR rates were 4.4% and 5.9%, respectively. The crude LRR rate for the TN patients was 7.4%, and the 3-year actuarial rate was 10.1%. The hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) patients had a crude LRR rate of 2.8% and a 3-year actuarial rate of 3.2%. The HER2+ patients had a crude LRR rate of 2.7% and a 3-year actuarial rate of 3.3%. Locoregional recurrence is uncommon for patients with node-negative HR+/HER2− and HER2+ tumors who have residual disease in the breast; however, TN patients have LRR rates that approach 10% at 3 years, suggesting a possible role for PMRT/RNI for node-negative TN patients. Additional follow-up with more patients is needed for definitive conclusions.

Breast cancer is still the most common cancer worldwide. But the way breast cancer is viewed has changed drastically since its molecular hallmarks were extensively characterised, now including immunohistochemical markers (eg, ER, PR, HER2 [ERBB2], and proliferation marker protein Ki-67 [MKI67]), genomic markers (eg, BRCA1, BRCA2, and PIK3CA), and immunomarkers (eg, tumour-infiltrating lymphocytes and PD-L1). New biomarker combinations are the basis for increasingly complex diagnostic algorithms. Neoadjuvant combination therapy, often including targeted agents, is a standard of care (especially in HER2-positive and triple-negative breast cancer), and the basis for de-escalation of surgery in the breast and axilla and for risk-adapted post-neoadjuvant strategies. Radiotherapy remains an important cornerstone of breast cancer therapy, but de-escalation schemes have become the standard of care. ER-positive tumours are treated with 5-10 years of endocrine therapy and chemotherapy, based on an individual risk assessment. For metastatic breast cancer, standard therapy options include targeted approaches such as CDK4 and CDK6 inhibitors, PI3K inhibitors, PARP inhibitors, and anti-PD-L1 immunotherapy, depending on tumour type and molecular profile. This range of treatment options reflects the complexity of breast cancer therapy today.

Background Within the multidisciplinary management of breast cancer, variations exist in the reconstructive options offered and care provided. The authors evaluated plastic surgeon perspectives on important issues related to breast cancer management and reconstruction and provide some insight into factors that influence these perspectives. Methods Women diagnosed with early-stage breast cancer (stages 0 to II) between July of 2013 and September of 2014 were identified through the Georgia and Los Angeles Surveillance, Epidemiology, and End Results registries. These women were surveyed and identified their treating plastic surgeons. Surveys were sent to the identified plastic surgeons to collect data on specific reconstruction practices. Results Responses from 134 plastic surgeons (74.4 percent response rate) were received. Immediate reconstruction (79.7 percent) was the most common approach to timing, and expander/implant reconstruction (72.6 percent) was the most common technique reported. Nearly one-third of respondents (32.1 percent) reported that reimbursement influenced the proportion of autologous reconstructions performed. Most (82.8 percent) reported that discussions about contralateral prophylactic mastectomy were initiated by patients. Most surgeons (81.3 to 84.3 percent) felt that good symmetry is achieved with unilateral autologous reconstruction with contralateral symmetry procedures in patients with small or large breasts; a less pronounced majority (62.7 percent) favored unilateral implant reconstructions in patients with large breasts. In patients requiring postmastectomy radiation therapy, one-fourth of the surgeons (27.6 percent) reported that they seldom recommend delayed reconstruction, and 64.9 percent reported recommending immediate expander/implant reconstruction. Conclusions Reconstructive practices in a modern cohort of plastic surgeons suggest that immediate and implant reconstructions are performed preferentially. Respondents perceived a number of factors, including surgeon training, time spent in the operating room, and insurance reimbursement, to negatively influence the performance of autologous reconstruction.

Neoadjuvant chemotherapy (NAC) has been proven to increase breast-conserving surgery (BCS) rates, but data are limited on conversion rates from BCS-ineligible (BCSi) to BCS-eligible (BCSe), specifically, in patients with large tumors. Consecutive patients with stage I–III breast cancer treated with NAC from November 2013 to March 2019 were identified. BCS eligibility before and after NAC was prospectively determined. Patients deemed BCSi before NAC due to large tumor size were studied. Statistical analyses were conducted using Student’s t-test, Wilcoxon rank sum test, Chi-square test, Fisher’s test, and logistic regression. In this study, 600 of 1353 cancers were BCSi with large tumors; 69% were non-BCS candidates, 31% were borderline-BCS (bBCS) candidates. Of non-BCS candidates, 69% became BCSe after NAC; 66% chose BCS, and 90% were successful. Among bBCS candidates, 87% were BCSe after NAC, 73% chose BCS, and 96% were successful. On univariate analysis, bBCS candidacy, lower cT stage, cN0 status, absence of calcifications, human epidermal growth factor receptor 2 positive (HER2+)/triple negative (TN) receptor status, poor differentiation, ductal histology, and breast pCR were associated with conversion to BCS eligibility. On multivariable analysis, receptor status (hormone receptor positive [HR+]/HER2– ref; odds ratio [OR] HER2+ 1.63, P = 0.047; HR–/HER2– OR, 2.26, P = 0.003) and breast pCR (OR 2.62, P

IMPORTANCE: The increasing use of germline genetic testing may have unintended consequences on treatment. Little is known about how women with pathogenic variants in cancer susceptibility genes are treated for breast cancer. OBJECTIVE: To determine the association of germline genetic testing results with locoregional and systemic therapy use in women diagnosed with breast cancer. DESIGN, SETTING, AND PARTICIPANTS: For this population-based cohort study, data from women aged 20 years or older who were diagnosed with stages 0 to III breast cancer between 2014 and 2016 were accrued from the Surveillance, Epidemiology and End Results (SEER) registries of Georgia and California. The women underwent genetic testing within 3 months after diagnosis and were reported to the Georgia and California SEER registries by December 1, 2017. EXPOSURES: Pathogenic variant status based on linked results of clinical germline genetic testing by 4 laboratories that did most such testing in the studied regions. MAIN OUTCOMES AND MEASURES: Potential deviation of treatment from practice guidelines was assessed in the following clinical scenarios: (1) surgery: receipt of bilateral mastectomy by women eligible for less extensive unilateral surgery (unilateral breast tumor); (2) radiotherapy: omission in women indicated for postlumpectomy radiotherapy (all lumpectomy recipients except age ≥70 with stage I, estrogen and/or progesterone receptor [ER/PR] positive, ERBB2 [formerly HER2]-negative disease); and (3) chemotherapy: receipt by women eligible to consider chemotherapy omission (stages I-II, ER/PR-positive, ERBB2-negative, and 21-gene recurrence score of 0-30, which was the upper limit of the intermediate risk range during the study years). The adjusted percentage treated and adjusted odds ratio (OR) are reported based on multivariable modeling for each treatment-eligible group. RESULTS: A total of 20 568 women (17.3%) of 119 198 were eligible (mean [SD] age, 51.4 [12.2]). Compared with women whose test results were negative, those with BRCA1/2 pathogenic variants were more likely to receive bilateral mastectomy for a unilateral tumor (61.7% vs 24.3%; OR, 5.52, 95% CI, 4.73-6.44), less likely to receive postlumpectomy radiotherapy (50.2% vs 81.5%; OR, 0.22, 95% CI, 0.15-0.32), and more likely to receive chemotherapy for early-stage, ER/PR-positive disease (38.0% vs 30.3%; OR, 1.76, 95% CI, 1.31-2.34). Similar patterns were seen with pathogenic variants in other breast cancer–associated genes (ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, and TP53) but not with variants of uncertain significance. CONCLUSIONS AND RELEVANCE: Women with pathogenic variants in BRCA1/2 and other breast cancer–associated genes were found to have distinct patterns of breast cancer treatment; these may be less concordant with practice guidelines, particularly for radiotherapy and chemotherapy.

BACKGROUND: In breast cancer surgery, patient-reported outcome measures (PROMs) are needed to measure outcomes that are best reported by patients (e.g., psychosocial well-being). The purpose of this study was to develop and validate a new BREAST-Q module to address the unique concerns of patients undergoing breast-conserving therapy (BCT). METHODS: Phase I involved qualitative and cognitive interviews with women who had BCT and clinical expert input to establish content for the BCT module. A field-test (Phase II) was performed and Rasch Measurement Theory (RMT) analysis was used for item reduction and to examine reliability and validity. Validation of the item-reduced scales in a clinical sample (Phase III) was conducted to further assess their psychometric properties. RESULTS: Qualitative interviews with 24 women resulted in the addition of 15 new items across multiple existing BREAST-Q scales and the development of 2 new scales (adverse effects of radiation and satisfaction with information - radiation therapy). Feedback from patients (n=15) and clinical experts (n=5) were used to refine the instructions, response options, and item wording. RMT analysis of data from 3,497 women resulted in item reduction. The final set of scales evidenced ordered response option thresholds, good item fit, and good reliability, with the exception of the adverse effects of radiation scale. Validity and reliability were further supported by the Phase III data from 3,125 women. CONCLUSIONS: The BREAST-Q BCT module can be used in research and in clinical care to evaluate quality metrics and to compare surgical outcomes across all breast cancer surgery patients.

Background Epidemiological and self-reported data suggest that Black women may be at increased risk of developing breast cancer related lymphedema (BCRL) after axillary lymph node dissection (ALND), however prospective clinical data is lacking. BCRL risk for other racial minorities has not been well studied. We sought to evaluate the impact of race and ethnicity on BCRL incidence and severity in a prospective cohort of patients treated with ALND using defined measurement protocols. Methods Patients undergoing ALND were enrolled in a prospective BCRL screening study with arm volume (perometer) measurements and body mass index (BMI) evaluated at baseline, post-operatively, and at 6-month intervals. BCRL was defined as a relative volume change (RVC) ≥ 10% from baseline. Groups were compared using Wilcoxon rank-sum and Fischer’s exact tests. Univariate (UVA) and multivariable analysis (MVA) were used to calculate the odds ratio (OR) of developing BCRL and to compare severity of BCRL. Results From 11/2016-03/2020, 304 patients were enrolled; 268 had at least one longitudinal measurement after baseline and are included in the study. Sixty-two percent of patients were Caucasian, 21% were Black, 11% were Asian and 6% were Hispanic. Black women were older (p = 0.007), had higher baseline BMI (p < 0.001), and were more likely to be clinically node-positive (p = 0.016) compared to Caucasian, Asian and Hispanic women. Both Black and Hispanic women were more likely to undergo breast-conserving surgery (p = 0.037) and receive nodal RT (p = 0.02) (Table). At a median follow-up of 1.62 years, 50 women developed BCRL. The 18-month BCRL rate for the entire cohort was 15.9% (95%CI, 11.5% - 21.8%). Black and Hispanic women had a higher incidence of BCRL compared to Asian and Caucasian women (18-month-rate: 30.9 % [Black]; 20.2% [Hispanic] vs 10.6% [Asian]; 11.8% [Caucasian], p = 0.004). On MVA, Black race was the strongest predictor of BCRL development (Caucasian [referent]): OR 4.41, 95%CI 2.42-8.10; p < 0.001); Asian race and Hispanic ethnicity were not associated with BCRL. Other factors, including receipt of NAC (upfront surgery [referent]): OR 1.89, 95%CI 1.02-3.63; p = 0.043), older age (1.04, 95%CI 1.01-1.06; per 1-year increase), increasing number of lymph nodes removed (OR 1.05, 95%CI 1.01-1.09 per 1 additional lymph node; p = 0.007) and a longer follow-up interval (OR 1.60, 95%CI 1.31-1.96 per 6-month increase; p < 0.001) were also independently associated with BCRL development. When assessing BCRL severity, Black women were 3.85 times more likely to have a higher relative volume change compared to Caucasian women (p = 0.007), with no difference in BCRL severity identified in Hispanic and Asian women (p = NS). Conclusions In this prospective screening study, Black and Hispanic women had a higher incidence of BCRL development compared to Caucasian women, with Black race being the strongest predictor of BCRL development and of severe BCRL. Further work should address the biologic mechanisms behind racial disparities in the risk of BCRL and possible preventive strategies. Table: Clinical Characteristics of study cohort stratified by race/ethnicityOverall#(n = 268)Caucasian(n = 161)Black (n = 54)Asian(n = 29)Hispanic (n = 16)P-valueAge (years)48. (40,57)49. (40,59)50. (42,55)44. (35,52)44. (33,49)0.007Baseline BMI (kg/m2)26.2. (22.5,31.1)25.2. (22.4,30.4)29.9. (25.9,34.0)22.1. (20.6,29.1)28.1. (23.5, 32.9)< 0.001cT. 1/2. 3/4180 (67%). 88 (33%)103 (64%). 58 (36%)36 (67%). 18 (33%)25 (86%). 4 (14%)12 (75%). 4 (25%)0.5cN. 0. 1. 2/372 (27%). 173 (65%). 23 (9%)46 (29%). 102 (63%). 13 (8%)8 (15%). 45 (83%). 1 (2%)12 (41%). 14 (48%). 3 (11%)3 (19%). 9 (56%). 4 (25%)0.016Histology. Ductal. Lobular or mixed. Other220 (82%). 36 (13%). 12(4.5%)128 (80%). 25 (16%). 8 (5.0%)47 (87%). 5 (9.3%). 2 (3.7%)25 (86%). 2 (6.9%). 2 (6.9%)12 (75%). 4 (25%). 0 (0%)0.5Subtype. HR+/HER2-. HER2+. HR-/HER2-181 (68%). 51 (19%). 36 (13%)111 (69%). 34 (21%). 16 (10%)31 (57%). 9 (17%). 14 (26%)23 (79%). 4 (14%). 2 (7%)10 (62%). 4 (25%). 2 (12%)0.1Chemotherapy. Neoadjuvant. Adjuvant190 (71%). 78(29%)111 (69%). 50 (31%)42(78%). 12(22%)17(59%). 12(41%)14(88%). 2(12%)0.12Type of Surgery. BCS. Mastectomy67 (25%). 201 (75%)36 (22%). 125 (78%)19 (35%). 35 (65%)3(10%). 26 (90%)6(38%). 10 (62%)0.037Type of Reconstruction†. None. Autologous/flap. TE/implant55 (27%). 23 (11%). 123 (61%)36 (29%). 11(9%). 78 (63%)9 (26%). 8 (23%). 18 (51%)8 (31%). 2(7%). 16 (62%)1(10%). 1 (10%). 8 (80%)0.083Total number of lymph nodes removed18 (14,23)19 (14,24)17 (13,22)15 (12,23)22 (18,24)0.059Total number of positive nodes2 (1, 5)3 (1, 6)2 (1, 3)2 (1, 4)2 (1, 3)0.073Radiation therapy††252 (94%)149 (93%)54 (100%)26 (90%)16 (100%)0.070Nodal RT244 (91%)145 (90%)53 (98%)23 (79%)16 (100%)0.020BCS, breast conserving surgery; TE, tissue expander Frequency (column percent) reported for categorical variables and median (IQR) reported for continuous variables #Race/ethnicity was unknown in 8 cases †Applies to mastectomy only ††Includes any type of radiation Citation Format: Andrea V. Barrio, Giacomo Montagna, Varadan Sevilimedu, Ethan A. Gomez, Babak Mehrara, Monica Morrow. Impact of race and ethnicity on incidence and severity of breast cancer related lymphedema after axillary lymph node dissection: Results of a prospective screening study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS4-01.

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.

Breast cancer treatment is multidisciplinary. The majority of women with early-stage breast cancer are candidates for breast-conserving surgery with radiotherapy or mastectomy. The risk of local recurrence and the chance of survival does not differ with these approaches. Sentinel node biopsy is used for axillary staging, and individualized approaches are minimizing the need for axillary dissection in sentinel node-positive women. Adjuvant systemic therapy is used in the majority of women based on proven survival benefit, and molecular profiling to individualize treatment based on risk is now a clinical reality for patients with hormone receptor-positive cancers. Follow-up surveillance consists of a history, physical examination, and annual mammography. Following adjuvant systemic treatment, there is currently no evidence that routine imaging improves outcomes in the absence of symptoms. Novel modalities for early tumor detection are welcomed, but will need to demonstrate clinical utility in prospective trials.

Purpose Little is known about the extent to which genetic counseling is integrated into community practices for patients newly diagnosed with breast cancer. We examined the receipt of clinically indicated genetic counseling in these patients. Patients and Methods We surveyed 5,080 patients between the ages of 20 and 79 years, diagnosed from July 2013 to August 2015 with early-stage breast cancer and reported to the SEER registries of Georgia and Los Angeles County. Surveys were linked to SEER clinical data and genetic test results. The study sample (N = 1,711) comprised patients with indications for formal genetic risk evaluation. Results Overall, 47.4% did not get tested, 40.7% tested negative, 7.4% had a variant of uncertain significance only, and 4.5% had a pathogenic mutation. Three quarters (74.6%) received some form of genetic counseling (43.5%, formal counseling and 31.1%, physician-directed discussion). Virtually all tested patients (96.1%) reported some form of genetic discussion (62.2%, formal counseling and 33.9%, physician-directed discussion). However, only one half (50.6%) of those not tested received any discussion about genetics. Younger women were more likely to report some type of counseling, controlling for other factors: odds ratio, 4.5 (95% CI, 2.6 to 8.0); 1.9 (95% CI, 1.1 to 3.3); and 1.5 (95% CI, 1.0 to 2.3) for women younger than 50 years of age, 50 to 59 years of age, and 60 to 69 years of age versus those 70 years of age and older. Patients’ assessments of the amount of information they received about whether to get tested were similarly high whether they were counseled by a genetics expert or by a physician only (80.8% v 79.4% stated information was just right, P = .59). Conclusion Less than one half (43.5%) of patients with clinical indications received formal genetic counseling. There is a large gap between mandates for timely pretest formal genetic counseling in higher-risk patients and the reality of practice today.

BACKGROUND The omission of radiotherapy (RT) after lumpectomy is a reasonable option for many older women with favorable-prognosis breast cancer. In the current study, we sought to evaluate patient perspectives regarding decision making about RT. METHODS Women aged 65 to 79 years with AJCC 7th edition stage I and II breast cancer who were reported to the Georgia and Los Angeles County Surveillance, Epidemiology, and End Results registries were surveyed (response rate, 70%) regarding RT decisions, the rationale for omitting RT, decision-making values, and understanding of disease recurrence risk. We also surveyed their corresponding surgeons (response rate, 77%). Patient characteristics associated with the omission of RT were evaluated using multilevel, multivariable logistic regression, accounting for patient clustering within surgeons. RESULTS Of 999 patients, 135 omitted RT (14%). Older age, lower tumor grade, and having estrogen receptor-positive disease each were found to be strongly associated with omission of RT in multivariable analyses, whereas the number of comorbidities was not. Non-English speakers were more likely to omit RT (adjusted odds ratio, 5.9; 95% confidence interval, 1.4-24.5). The most commonly reported reasons for RT omission were that a physician advised the patient that it was not needed (54% of patients who omitted RT) and patient choice (41%). Risk of local disease recurrence was overestimated by all patients: by approximately 2-fold among those who omitted RT and by approximately 8-fold among those who received RT. The risk of distant disease recurrence was overestimated by approximately 3-fold on average. CONCLUSIONS To some extent, decisions regarding RT omission are appropriately influenced by patient age, tumor grade, and estrogen receptor status, but do not appear to be optimally tailored according to competing comorbidities. Many women who are candidates for RT omission overestimate their risk of disease recurrence. Cancer 2018;124:2714-2723. © 2018 American Cancer Society.

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

Purpose This study was conducted to determine the effect of iCanDecide, an interactive and tailored breast cancer treatment decision tool, on the rate of high-quality patient decisions—both informed and values concordant—regarding locoregional breast cancer treatment and on patient appraisal of decision making. Methods We conducted a randomized clinical trial of newly diagnosed patients with early-stage breast cancer making locoregional treatment decisions. From 22 surgical practices, 537 patients were recruited and randomly assigned online to the iCanDecide interactive and tailored Web site (intervention) or the iCanDecide static Web site (control). Participants completed a baseline survey and were mailed a follow-up survey 4 to 5 weeks after enrollment to assess the primary outcome of a high-quality decision, which consisted of two components, high knowledge and values-concordant treatment, and secondary outcomes (decision preparation, deliberation, and subjective decision quality). Results Patients in the intervention arm had higher odds of making a high-quality decision than did those in the control arm (odds ratio, 2.00; 95% CI, 1.37 to 2.92; P = .0004), which was driven primarily by differences in the rates of high knowledge between groups. The majority of patients in both arms made values-concordant treatment decisions (78.6% in the intervention arm and 81.4% in the control arm). More patients in the intervention arm had high decision preparation (estimate, 0.18; 95% CI, 0.02 to 0.34; P = .027), but there were no significant differences in the other decision appraisal outcomes. The effect of the intervention was similar for women who were leaning strongly toward a treatment option at enrollment compared with those who were not. Conclusion The tailored and interactive iCanDecide Web site, which focused on knowledge building and values clarification, positively affected high-quality decisions largely by improving knowledge compared with static online information. To be effective, future patient-facing decision tools should be integrated into the clinical workflow to improve decision making.

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.

The appropriate negative margin width for women undergoing breast-conserving surgery for both ductal carcinoma in situ (DCIS) and invasive carcinoma is controversial. This review examines the available data on the margin status for invasive breast cancer and DCIS, and highlights the similarities and differences in tumor biology and standard treatments that affect the local recurrence (LR) risk and, therefore, the optimal surgical margin. Consensus guidelines support a negative margin, defined as no ink on tumor, for invasive carcinoma treated with breast-conserving therapy. Because of differences in the growth pattern and utilization of systemic therapy, a margin of 2 mm has been found to minimize the LR risk for women with DCIS undergoing lumpectomy and radiation therapy (RT). Wider negative margins do not improve local control for DCIS or invasive carcinoma when they are treated with lumpectomy and RT. Re-excision for negative margins should be individualized, and the routine practice of performing additional surgery to obtain a wider negative margin is not supported by the literature. Cancer 2018;124:1335-41. © 2018 American Cancer Society.

Background The 21-gene recurrence score (RS) assay determines the benefit of adding chemotherapy to endocrine therapy for patients with early stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. The RS risk groups predict the likelihood of distant recurrence and have recently been associated with an increased risk of locoregional recurrence (LRR). This study analyzed clinicopathologic features of patients with low RS and LRR. Methods In our institutional database, we identified 1396 consecutive female patients with lymph node negative, ER+/HER2- invasive breast carcinoma and low RS (

Background: Four prospective multi-institutional trials have demonstrated that clinically node-positive patients (cN1) who receive neoadjuvant therapy (NAC) and convert to cN0 can be reliably staged with sentinel lymph node biopsy (SLNB) with false-negative rates (FNRs) of < 10%, when ≥ 3 SLNs are retrieved. Since study patients all had axillary lymph node dissection (ALND), the rate of axillary recurrence after SLNB alone is unknown. Of concern is the possibility that residual chemotherapy-resistant axillary disease could lead to higher recurrence rates than seen in the primary surgery setting for cN0 patients where SLN FNRs of 5-10% result in axillary recurrence in < 1% of cases. Here we report regional recurrence rates in a prospectively defined cohort of cN1 patients receiving NAC, followed by a negative SLNB using a standardized technique, and no further axillary surgery. Methods: From 06/2014 to 02/2019, patients with cT1-3 biopsy-proven cN1 breast cancer who received NAC and converted to cN0 by physical exam were prospectively managed with SLNB with dual tracer mapping and omission of ALND if ≥ 3 SLNs were pathologically negative. Nodes were not routinely clipped, and retrieval of clipped metastatic nodes was not required. Pathologically negative SLNs were defined as the absence of any metastases including isolated tumor cells. Results: Of 610 cN1 patients treated with NAC, 555 (91%) converted to cN0 and had SLNB; 234 (42%) had ≥ 3 negative SLNs and were treated with SLNB alone. Median patient age was 49 years and median tumor size at presentation was 3 cm; 61% were HER2+ and 18% triple negative. Most (91%) received doxorubicin-based NAC and 88% received adjuvant radiotherapy (RT), with 80% (n = 164) of RT patients receiving nodal RT (Table). At a median follow-up of 35 months, there was only 1 (0.4%) axillary recurrence for the entire cohort, synchronous with a breast recurrence, in a patient who refused RT. Among patients who received RT (n = 205), there were no axillary recurrences. The 4-year rate of distant recurrence for all patients was 6.1% (95% CI, 3.4-10.7%) and 4-year overall survival was 93.9% (95% CI, 87.6-97.1%). Conclusion: In cN1 patients treated with NAC, rates of axillary recurrence in patients with ≥ 3 pathologically negative SLNs treated with SLNB alone were low, without routine nodal clipping. Although further follow-up is needed, multiple studies have shown that nodal recurrence is an early event, particularly in HER2+ and triple negative patients, who comprised the majority of the population. Our findings support omitting ALND in cN1 patients after NAC when the SLNs are negative using an optimal SLNB technique. Table. Patient PopulationOverall cohort (n = 234)Age, years (median, IQR)49 (40, 58)Tumor size at presentation, cm (median, IQR)3.0 (2.2, 5.0)Number SLNs retrieved (median, IQR)4 (3, 5)Palpable nodes at presentation (n, %)179 (76%)HistologyDuctal211 (90%)Lobular and mixed7 (3%)Micropapillary and mixed10 (4%)Other3 (1%)Occult3 (1%)DifferentiationWell1 (0.5%)Moderate36 (15%)Poor196 (84%)Unknown1 (0.5%)Receptor StatusHR+/HER2-47 (20%)HR+/HER2+80 (34%)HR-/HER2+64 (27%)HR-/HER2-43 (18%)Breast SurgeryBCS118 (50%)Mastectomy116 (50%)Breast pCR¥Yes161 (70%)No70 (30%)NAC regimenAC-T197 (84%)AC-T + carbo15 (6.4%)TC8 (3.4%)Other14 (6%)Neoadjuvant anti-HER2 treatmentHP (dual-therapy)144 (100%)Adjuvant RTYes205 (88%)No*29 (12%)¥3 patients had occult primary breast cancer and were not included in breast pCR calculation; *6/29 patients who did not receive RT enrolled in NSABP B-51 Citation Format: Andrea V Barrio, Giacomo Montagna, Anita Mamtani, Varadan Sevilimedu, Hiram S Cody, III, Mahmoud El-Tamer, Mary L Gemignani, Alexandra S Heerdt, Tracy-Ann Moo, Melissa Pilewskie, George Plitas, Lisa Sclafani, Kimberly J Van Zee, Monica Morrow. Axillary recurrence is a rare event in node-positive patients. treated with sentinel node biopsy alone after neoadjuvant chemotherapy: Results of a prospective study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-05.

Background: Genetic testing is increasingly important for breast and ovarian cancer risk reduction and treatment. However, little is known about trends and disparities in receipt of testing in the community and test results after diagnosis. Methods: We linked records of all women with breast cancer or ovarian cancer diagnosed from 2013-2017 in Georgia and California and reported to Surveillance, Epidemiology and End Results (SEER) registries to genetic testing results from four laboratories that did most clinical testing in the studied regions (Ambry Genetics, GeneDx, Invitae, Myriad Genetics). We combined test results performed by all laboratories over 2012-2019 with SEER data. We measured use of any test, median number of genes tested, rates of variants of uncertain significance (VUS) and pathogenic variants (PVs). Results: A total of 25.2% of 187,535 breast cancer patients, and 34.3% of 14,689 ovarian cancer patients, had genetic testing. Testing increased annually by 2% while the median number of genes tested increased annually by 28%. Among tested patients diagnosed with breast cancer in 2017, 5.2% had BRCA1/2 PVs while 4.9% had PVs in genes associated with a recognized cancer syndrome (APC, CDH1, MLH1, MSH2, MSH6, NF1, PMS2, PTEN, RET and TP53) or with emerging evidence for an increased risk of breast cancer and/or ovarian cancer (ATM, BARD1, BRIP1, CHEK2, NBN, PALB2, RAD51C and RAD51D). Among tested patients diagnosed with ovarian cancer in 2017, 11.0% had BRCA1/2 PVs while 2.3% had PVs in a syndromic gene (APC, MLH1, MSH2, MSH6, NF1, PMS2, and TP53) or an emerging breast/ovarian cancer gene (ATM, BARD1, BRIP1, CHEK2, NBN, PALB2, RAD51C and RAD51D). PVs in other tested genes were rare (generally Citation Format: Allison W Kurian, Monica Morrow, Steven Katz. Trends in genetic testing and results for women diagnosed with breast cancer or ovarian cancer, 2013-2017 [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD10-01.

Obesity (body mass index (BMI)⩾30 kg m−2) is associated with an increased risk of estrogen-dependent breast cancer after menopause. Levels of aromatase, the rate-limiting enzyme in estrogen biosynthesis, are elevated in breast tissue of obese women. Recently, the regulation of aromatase by the p53-hypoxia-inducible factor-1α (HIF1α)/pyruvate kinase M2 (PKM2) axis was characterized in adipose stromal cells (ASCs) of women with Li–Fraumeni Syndrome, a hereditary cancer syndrome that predisposes to estrogen-dependent breast cancer. The current study aimed to determine whether stimulation of aromatase by obesity-associated adipokine leptin involves the regulation of the p53-HIF1α/PKM2 axis. Human breast ASCs were used to characterize the p53-HIF1α/PKM2-aromatase axis in response to leptin. The effect of pharmacological or genetic modulation of protein kinase C (PKC), mitogen-activated protein kinase (MAPK), p53, Aha1, Hsp90, HIF1α and PKM2 on aromatase promoter activity, expression and enzyme activity was examined. Semiquantitative immunofluorescence and confocal imaging were used to assess ASC-specific protein expression in formalin-fixed paraffin-embedded tissue sections of breast of women and mammary tissue of mice following a low-fat (LF) or high-fat (HF) diet for 17 weeks. Leptin-mediated induction of aromatase was dependent on PKC/MAPK signaling and the suppression of p53. This, in turn, was associated with an increase in Aha1 protein expression, activation of Hsp90 and the stabilization of HIF1α and PKM2, known stimulators of aromatase expression. Consistent with these findings, ASC-specific immunoreactivity for p53 was inversely associated with BMI in breast tissue, while HIF1α, PKM2 and aromatase were positively correlated with BMI. In mice, HF feeding was associated with significantly lower p53 ASC-specific immunoreactivity compared with LF feeding, while immunoreactivity for HIF1α, PKM2 and aromatase were significantly higher. Overall, findings demonstrate a novel mechanism for the obesity-associated increase in aromatase in ASCs of the breast and support the study of lifestyle interventions, including weight management, which may reduce breast cancer risk via effects on this pathway.

BACKGROUND Many patients with breast cancer work for pay at the time of their diagnosis, and the treatment plan may threaten their livelihood. Understanding work experiences in a contemporary population-based sample is necessary to inform initiatives to reduce the burden of cancer care. METHODS Women who were 20 to 79 years old and had been diagnosed with stage 0 to II breast cancer, as reported to the Georgia and Los Angeles Surveillance, Epidemiology, and End Results registries in 2014-2015, were surveyed. Of the 3672 eligible women, 2502 responded (68%); 1006 who reported working before their diagnosis were analyzed. Multivariate models evaluated correlates of missing work for >1 month and stopping work altogether versus missing work for ≤1 month. RESULTS In this diverse sample, most patients (62%) underwent lumpectomy; 16% underwent unilateral mastectomy (8% with reconstruction); and 23% underwent bilateral mastectomy (19% with reconstruction). One-third (33%) received chemotherapy. Most (84%) worked full-time before their diagnosis; however, only 50% had paid sick leave, 39% had disability benefits, and 38% had flexible work schedules. Surgical treatment was strongly correlated with missing >1 month of work (odds ratio [OR] for bilateral mastectomy with reconstruction vs lumpectomy, 7.8) and with stopping work altogether (OR for bilateral mastectomy with reconstruction vs lumpectomy, 3.1). Chemotherapy receipt (OR for missing >1 month, 1.3; OR for stopping work altogether, 3.9) and race (OR for missing >1 month for blacks vs whites, 2.0; OR for stopping work altogether for blacks vs whites, 1.7) also correlated. Those with paid sick leave were less likely to stop working (OR, 0.5), as were those with flexible schedules (OR, 0.3). CONCLUSIONS Working patients who received more aggressive treatments were more likely to experience substantial employment disruptions. Cancer 2017. © 2017 American Cancer Society.

A cancer in the contralateral breast in a woman with a previous or synchronous breast cancer is typically considered to be an independent primary tumor. Emerging evidence suggests that in a small subset of these cases the second tumor represents a metastasis. We sought to investigate the issue using massively parallel sequencing targeting 254 genes recurrently mutated in breast cancer. We examined the tumor archives at Memorial Sloan Kettering Cancer Center for the period 1995-2006 to identify cases of contralateral breast cancer where surgery for both tumors was performed at the Center. We report results from 49 patients successfully analyzed by a targeted massively parallel sequencing assay. Somatic mutations and copy number alterations were defined by state-of-the-art algorithms. Clonal relatedness was evaluated by statistical tests specifically designed for this purpose. We found evidence that the tumors in contralateral breasts were clonally related in three cases (6%) on the basis of matching mutations at codons where somatic mutations are rare. Clinical data and the presence of similar patterns of gene copy number alterations were consistent with metastasis for all three cases. In three additional cases, there was a solitary matching mutation at a common PIK3CA locus. The results suggest that a subset of contralateral breast cancers represent metastases rather than independent primary tumors. Massively parallel sequencing analysis can provide important evidence to clarify the diagnosis. However, given the inter-tumor mutational heterogeneity in breast cancer, sufficiently large gene panels need to be employed to define clonality convincingly in all cases.

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

BACKGROUND Little is known about how the individual decision styles and values of breast cancer patients at the time of treatment decision making are associated with the consideration of different treatment options and specifically with the consideration of contralateral prophylactic mastectomy (CPM). METHODS Newly diagnosed patients with early-stage breast cancer who were treated in 2013-2014 were identified through the Surveillance, Epidemiology, and End Results registries of Los Angeles and Georgia and were surveyed approximately 7 months after surgery (n = 2578; response rate, 71%). The primary outcome was the consideration of CPM (strong vs less strong). The association between patients' values and decision styles and strong consideration was assessed with multivariate logistic regression. RESULTS Approximately one-quarter of women (25%) reported strong/very strong consideration of CPM, and another 29% considered it moderately/weakly. Decision styles, including a rational-intuitive approach to decision making, varied. The factors most valued by women at the time of treatment decision making were as follows: avoiding worry about recurrence (82%) and reducing the need for more surgery (73%). In a multivariate analysis, patients who preferred to make their own decisions, those who valued avoiding worry about recurrence, and those who valued avoiding radiation significantly more often strongly considered CPM (P < .05), whereas those who reported being more logical and those who valued keeping their breast did so less often. CONCLUSIONS Many patients considered CPM, and the consideration was associated with both decision styles and values. The variability in decision styles and values observed in this study suggests that formally evaluating these characteristics at or before the initial treatment encounter could provide an opportunity for improving patient clinician discussions. Cancer 2017;123:4547-4555. © 2017 American Cancer Society.

In the setting of increased awareness regarding the need to address potential overtreatment in the management of breast cancer patients with favorable-prognosis disease, this article reviews three relevant instances in which the extent of surgery has been safely decreased: margin width in patients with ductal carcinoma in situ; axillary management in clinically node-negative women undergoing primary breast-conserving surgery; and the use of neoadjuvant chemotherapy followed by sentinel node biopsy for patients presenting with node-positive breast cancer. The management of the axillary nodes over the past decade highlights the potential to de-escalate surgery in the era of multimodality therapy. Similar opportunities exist for the use of radiotherapy. To fully realize the potential of de-escalating surgery, new communication strategies must be developed to convince patients that bigger is not necessarily better.

Women with ductal carcinoma in situ (DCIS) are increasingly choosing bilateral mastectomy. We sought to quantify rates of contralateral breast cancer (CBC) and ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) for DCIS, and to compare risk factors for CBC and IBTR. From 1978 to 2011, DCIS patients undergoing BCS with a contralateral breast at risk were identified from a prospectively maintained database. The association of clinicopathologic and treatment factors with CBC and IBTR were evaluated using Kaplan–Meier analysis, multivariable Cox regression, and competing risk regression (CRR). Of 2759 patients identified, 151 developed CBC and 344 developed IBTR. Five- and 10-year Kaplan–Meier CBC rates were 3.2 and 6.4%. Overall, 10-year IBTR rates were 2.5-fold higher than CBC rates, and, without radiation, 4-fold higher. On CRR, 5- and 10-year rates were 2.9 and 5.8% for CBC, and 7.8 and 14.5% for IBTR. CBC risk and invasive CBC risk were not significantly associated with age, family history, presentation, nuclear grade, year of surgery, or radiation. By multivariable Cox regression, endocrine therapy was associated with lower CBC risk (hazard ratio 0.57, p = 0.03). Ten-year risk of subsequent CBC in the subset of patients who developed IBTR was similar to the cohort as a whole (8.1 vs. 6.4%). CBC rates were low across all groups, including those who experienced IBTR. CBC was not associated with factors that increase IBTR risk. While factors associated with IBTR risk are important in decision making regarding management of the index DCIS, they are not an indication for contralateral prophylactic mastectomy.

Studies assessing outcomes in occult breast cancer have often included women treated before the routine use of magnetic resonance imaging (MRI). This study examined outcomes for patients presenting with axillary adenopathy and no primary breast tumor detectable by MRI or other imaging methods. All patients with axillary nodal metastases consistent with breast carcinoma and no breast primary tumor detectable by physical exam, mammography, or MRI treated between 1 January 1996 and 30 June 2011 were identified from an institutional database. Data were collected on local, regional, and distant recurrences. For the study, 38 patients were identified. Modified radical mastectomy (MRM) was performed for 13 of the patients, whereas 25 of the patients underwent axillary dissection (ALND) and whole-breast radiotherapy (WBRT). Most of the women had pathologic N1 disease [median number of positive nodes, 2 (MRM cohort) and 3 (ALND + WBRT cohort); p = 0.38]. All the patients received chemotherapy, and 30 (79%) of the 38 patients received an anthracycline and taxane. Regional nodal radiation was used for 60% of those with ALND + WBRT and for all 46% of the MRM patients who received chest wall radiotherapy. During a median follow-up period of 7 years, there were no nodal recurrences. Two patients treated with ALND + WBRT had in-breast recurrences, whereas none in the MRM group experienced a local recurrence. The proportion that experienced distant disease was similar between the MRM cohort (1 of 13) and the ALND + WBRT cohort (2 of 25). Breast cancer presenting as axillary adenopathy with no detectable primary tumor is rare. Breast conservation with WBRT is a viable option for patients with a diagnosis of occult breast cancer and a negative preoperative MRI.

Although there is no consensus on whether pre-operative MRI in women with breast cancer (BC) benefits surgical treatment, MRI continues to be used pre-operatively in practice. This meta-analysis examines the association between pre-operative MRI and surgical outcomes in BC. A systematic review was performed to identify studies reporting quantitative data on pre-operative MRI and surgical outcomes (without restriction by type of surgery received or type of BC) and using a controlled design. Random-effects logistic regression calculated the pooled odds ratio (OR) for each surgical outcome (MRI vs. no-MRI groups), and estimated ORs stratified by study-level age. Subgroup analysis was performed for invasive lobular cancer (ILC). Nineteen studies met eligibility criteria: 3 RCTs and 16 comparative studies that included newly diagnosed BC of any type except for three studies restricted to ILC. Primary analysis (85,975 subjects) showed that pre-operative MRI was associated with increased odds of receiving mastectomy [OR 1.39 (1.23, 1.57); p

The 21-gene recurrence score (RS) assay predicts the likelihood of distant recurrence and chemotherapy benefit in early-stage, estrogen receptor (ER)-positive, HER2-negative breast cancer. Data on the RS of special histologic subtypes of invasive breast carcinoma with favorable prognosis are limited. We reviewed our institutional database to identify patients with special histologic subtypes of breast cancer associated with favorable prognosis and available RS results. Our cohort consists of fifty-seven women: thirty-three patients with pure mucinous carcinoma (MC), ten with tubular carcinoma (TC), nine with encapsulated papillary carcinoma (EPC), and five with solid papillary carcinoma (SPC). Most (44/57, 77.2%) carcinomas had low RS (≤17), and none had high RS (≥31). All EPCs had low RS, but other subtypes had RS 18–30. Higher RS was associated with lower progesterone receptor (PR) expression by immunohistochemistry and lower PR mRNA scores (P ≤ 0.007). No morphologic feature (tumor grade, biopsy site changes, cellular stroma, inflammatory cells) was associated with RS ≥ 18. At a median follow-up of 40 months, the distant recurrence-free survival was 100%. One patient with SPC developed locoregional recurrence at 22 months. As the largest series to date, our study raises the question of whether the RS assay is necessary for breast cancers with favorable histology. Reflex testing of node-negative, ER+/HER2− breast cancers may be deferred for these special histologic subtypes, emphasizing the need for multidisciplinary discussions between breast pathologists and other members of the breast cancer team.

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.

Purpose of Review Ductal carcinoma in situ (DCIS) can be successfully treated with breast-conserving surgery (BCS); however, there is little consensus regarding what negative margin width minimizes the risk of local recurrence, and as many as one third of patients undergo additional surgery after initial lumpectomy.

Obesity is associated with breast white adipose tissue (WAT) inflammation, elevated levels of the estrogen biosynthetic enzyme, aromatase, and systemic changes that have been linked to the pathogenesis of breast cancer. Here, we determined whether metabolic obesity, including changes in breast biology and systemic effects, occurs in a subset of women with normal body mass index (BMI). Breast WAT and fasting blood were collected from 72 women with normal BMI ( See related article by Berger, p. 223–25.

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.

Usage of magnetic resonance imaging (MRI) in newly diagnosed breast cancer patients is increasing, despite scant evidence that it improves outcomes. Little is known about the knowledge, perspectives, and clinical characteristics of surgeons associated with MRI use. Women with early-stage breast cancer undergoing definitive surgery between July 2013 and August 2015 were identified from the Los Angeles and Georgia Surveillance, Epidemiology and End Results (SEER) registries and were asked to name their attending surgeons. The 489 surgeons were sent a questionnaire; 77% (n = 377) responded. Questions that addressed the likelihood of ordering an MRI in different scenarios were used to create a scale to measure surgeon propensity for MRI use. Knowledge and practice characteristics also were assessed. Mean surgeon age was 54 years, 25% were female, and median number of years in practice was 21. Wide MRI use variation was observed, with 26% obtaining MRI for a clinical stage I screen-detected breast cancer and 72% for infiltrating lobular cancer. High users of MRI were significantly more likely to be higher-volume surgeons (p

Background: The 21-gene recurrence score (RS) estimates the likelihood of distant recurrence and the benefit from chemotherapy in patients with early-stage node-negative, estrogen receptor (ER)-positive, HER2-negative breast carcinoma. The use of the assay resulted in a substantial reduction in adjuvant chemotherapy usage. In this study, we reviewed the outcome of patients with node-negative, ER+/HER2- breast cancer and low recurrence score treated at our center to further verify the prognostic value of the assay. Design: We identified breast cancer patients treated at our center between 09/2008 and 08/2013 with ER-positive, HER2-negative breast cancer and known RS. We reviewed clinicopathological characteristics, RS, treatment and outcome data. The Institutional Review Board approved the study. Results: We identified 1406 consecutive patients with early stage node negative ER+/HER2- breast cancer and low RS [RS 0-10: 510 (36%), RS 11-17: 896 (64%)] in the study period. The median age at breast cancer diagnosis was 56 years (range 22-90). Sixty-three (4%) patients were Conclusion: Our results suggest that young age ( Table 1. Clinicopathologic characteristics of the 6 patients with ER-positive, HER2-negative, node-negative breast carcinoma of recurrence score Citation Format: Wen HY, Krystel-¬Whittemore M, Patil S, Pareja F, Bowser ZL, Dickler M, Norton L, Morrow M, Hudis C, Brogi E. Breast carcinoma with 21-gene recurrence score lower than 18: Rate of distant metastases in a large series with clinical follow-up [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 P1-09-14.

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.