PURPOSE: To develop recommendations for germline mutation testing for patients with breast cancer. METHODS: An ASCO–Society of Surgical Oncology (SSO) panel convened to develop recommendations based on a systematic review and formal consensus process. RESULTS: Forty-seven articles met eligibility criteria for the germline mutation testing recommendations; 18 for the genetic counseling recommendations. RECOMMENDATIONS: BRCA1/ 2 mutation testing should be offered to all newly diagnosed patients with breast cancer ≤65 years and select patients >65 years based on personal history, family history, ancestry, or eligibility for poly(ADP-ribose) polymerase (PARP) inhibitor therapy. All patients with recurrent breast cancer who are candidates for PARP inhibitor therapy should be offered BRCA1/ 2 testing, regardless of family history. BRCA1/ 2 testing should be offered to women who develop a second primary cancer in the ipsilateral or contralateral breast. For patients with prior history of breast cancer and without active disease, testing should be offered to patients diagnosed ≤65 years and selectively in patients diagnosed after 65 years, if it will inform personal and family risk. Testing for high-penetrance cancer susceptibility genes beyond BRCA1/ 2 should be offered to those with supportive family histories; testing for moderate-penetrance genes may be offered if necessary to inform personal and family cancer risk. Patients should be provided enough pretest information for informed consent; those with pathogenic variants should receive individualized post-test counseling. Variants of uncertain significance should not impact management, and patients with such variants should be followed for reclassification. Referral to providers experienced in clinical cancer genetics may help facilitate patient selection and interpretation of expanded testing, and provide counseling of individuals without pathogenic germline variants but with significant family history. Additional information is available at www.asco.org/breast-cancer-guidelines .

Despite increased demand for contralateral prophylactic mastectomy (CPM), the survival benefit of this procedure remains uncertain. We used the Surveillance, Epidemiology, and End Results database to identify 107 106 women with breast cancer who had undergone mastectomy for treatment between 1998 and 2003 and a subset of 8902 women who also underwent CPM during the same period. Associations between predictor variables and the likelihood of undergoing CPM were evaluated by use of χ ² analyses. Risk-stratified (estrogen receptor [ER] status, stage, and age) adjusted survival analyses were performed by using Cox regression. Statistical tests were two-sided. In a univariate analysis, CPM was associated with improved disease-specific survival (hazard ratio [HR] of death = 0.63, 95% confidence interval [CI] = 0.57 to 0.69; P < .001). Risk-stratified analysis showed that this association was because of a reduction in breast cancer–specific mortality in women aged 18–49 years with stages I–II ER-negative cancer (HR of death = 0.68, 95% CI = 0.53 to 0.88; P = .004). Five year–adjusted breast cancer survival for this group was improved with CPM vs without (88.5% vs 83.7%, difference = 4.8%). Although rates of contralateral breast cancer among young women with stages I–II disease undergoing CPM were independent of ER status, women with ER-positive tumors in the absence of prophylactic mastectomy also had a lower overall risk for contralateral breast cancer than women with ER-negative tumors (0.46% vs 0.90%, difference = 0.44%; P < .001). CPM is associated with a small improvement in 5-year breast cancer–specific survival mainly in young women with early-stage ER-negative breast cancer. This effect is related to a higher baseline risk of contralateral breast cancer.

Introduction: Breast cancers of different molecular subtypes have different survival rates. The goal of this study was to identify patients at high risk for local-regional recurrence according to response to neoadjuvant chemotherapy and surrogate markers of molecular subtypes in patients undergoing breast conserving therapy (BCT). Methods: Clinicopathologic data from 595 breast cancer patients who received neoadjuvant chemotherapy and BCT from 1997 to 2005 were identified. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression determined by immunohistochemistry were used to construct the following subtypes: ER+ or PR+ and HER2- (hormone receptor (HR)+/HER2-; 52%), ER+ or PR+ and HER2+ (HR+/HER2+; 9%), ER- and PR- and HER2+ (HR-/HER2+; 7%) and ER- and PR- and HER2- (HR-/HER2-; 32%). Actuarial rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards models were used for multivariate analysis (MVA). Results: After a median follow-up of 64 months, the five-year local-regional recurrence (LRR)-free survival rate for all patients was 93.8%. The five-year LRR-free survival rates varied by subtype: HR+/HER2- 97.0%, HR+/HER2+ 95.9%, HR-/HER2+ 86.5% and HR-/HER2- 89.5% (P = 0.001). In addition to subtype, clinical stage III disease (90% vs. 95% for I/II, P = 0.05), high nuclear grade (92% vs. 97% with low/intermediate grade, P = 0.03), presence of lymphovascular invasion (LVI) (89% vs. 95% in those without LVI, P = 0.02) and four or more positive lymph nodes on pathologic examination (87% vs. 95% with zero to three positive lymph nodes, P = 0.03) were associated with lower five-year LRR-free survival on univariate analysis. On MVA, HR-/HER2+ and HR-/HER2- subtypes and disease in four or more lymph nodes were associated with decreased LRR-free survival. A pathologic complete response (pCR) was associated with improved LRR-free survival. Conclusions: Patients with HR+/HER2- and HR+/HER2+ subtypes had excellent LRR-free survival regardless of tumor response to neoadjuvant chemotherapy. Patients with HR-/HER2+ and HR-/HER2- subtypes with poor response to neoadjuvant chemotherapy had worse LRR-free survival after BCT. Additional study is needed to determine the impact of trastuzumab on local-regional control in HER2+ tumors. Our data suggest that patients with HR-/HER2- subtype tumors not achieving pCR may benefit from novel strategies to improve local-regional control.

With several randomized prospective trials^1,2confirming the efficacy of breast-conserving therapy (BCT), the National Institutes of Health (NIH)³ issued a consensus statement in 1990 in support of this treatment modality. These trials and the NIH consensus statement led to a substantial decline in the rates of mastectomy and the widespread acceptance of BCT as an appropriate treatment modality for early-stage breast cancer.⁴ However, during the past decade, technical advances and changes in societal norms may have created new incentives other than BCT, even among patients who remain good candidates for this treatment. These incentives include genetic testing for BRCA1 and BRCA2 mutation, advances in reconstruction techniques, breast magnetic resonance imaging, and increased patient interest in contralateral prophylactic mastectomy.

BACKGROUND: The 2015 National Comprehensive Cancer Network guidelines recommend that genetic counseling and germline BRCA mutation testing be offered to women under age 60 with triple‐negative breast cancer (TNBC). As a result of the 2010 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for breast cancer, patients with breast cancers that are estrogen receptor (ER) or progesterone receptor (PR) low‐positive (1%‐9% on immunohistochemistry) are no longer strictly considered to have TNBC and may not be referred for genetic counseling. However, the incidence of BRCA mutation in patients with hormone receptor (HR) low‐positive breast cancers remains unknown, and current ASCO/CAP guidelines may result in undertesting for BRCA mutations.METHODS: A prospectively maintained research database of breast cancer patients evaluated at The University of Texas MD Anderson Cancer Center between 2004 and 2014 was reviewed; 314 patients were identified with HER2/neu–negative breast cancers expressing ER and PR <10% with known BRCA mutation status.RESULTS: Three hundred fourteen patients had breast cancers expressing ER and PR <10%; 238 (75.8%) had HR‐negative cancers (<1% ER and PR), and 76 (24.2%) had HR–low‐positive cancers (1%‐9% ER and/or PR). Among patients with HR‐negative tumors, 86 of 238 (36.1%) had a BRCA1/2 mutation, whereas in the HR–low‐positive group, 30 of 76 (39.5%) had a BRCA1/2 mutation. In multivariate analysis, HR status (<1% vs 1%‐9%) was not significantly associated with BRCA1/2 mutations.CONCLUSIONS: The incidence of BRCA1/2 mutations is similar in patients with HR–low‐positive breast cancer and patients with HR‐negative breast cancer. Genetic counseling and BRCA testing should be offered to patients under age 60 who have HR–low‐positive breast cancers. Cancer 2015;121:3435–43. © 2015 American Cancer Society.

Purpose: Screening mammography guidelines for patients age 80 years and older are variable. We determined the effect of mammography use on stage at breast cancer diagnosis and survival among women of this age range. Patients and Methods: We used the linked Surveillance, Epidemiology, and End Results–Medicare database to evaluate 12,358 women ≥ 80 years of age diagnosed with breast cancer between 1996 and 2002. Patients were grouped according to number of mammograms during the 60 months before diagnosis: nonusers (0 mammograms), irregular users (one to two mammograms), and regular users (three or more mammograms). Effects of mammography on disease stage (I to IIa v IIb to IV) and survival were determined by logistic regression and Cox proportional hazards analyses. Results: Percentages of women with nonuse, irregular use, and regular use of mammography during the 5 years preceding diagnosis were 49%, 29%, and 22%, respectively. On multivariate analysis, patients were 0.37 times less likely to present with late-stage cancer for each mammogram obtained (odds ratio, 0.63; 95% CI, 0.63 to 0.67). Breast cancer–specific 5-year survival among nonusers was 82%, that among irregular users was 88%, and that among regular users was 94%. However, survival from causes other than breast cancer was also associated with mammography use, suggesting a bias for healthier patients to undergo mammography. Conclusion: Regular mammography among women ≥ 80 years of age was associated with earlier disease stage, although improved survival remains difficult to demonstrate. Health care providers should consider discussing the potential benefits of screening mammography with their older patients, particularly for those without significant comorbidity.