PURPOSE To develop recommendations for management of patients with breast cancer (BC) with germline mutations in BC susceptibility genes. METHODS The American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology convened an Expert Panel to develop recommendations based on a systematic review of the literature and a formal consensus process. RESULTS Fifty-eight articles met eligibility criteria and formed the evidentiary basis for the local therapy recommendations; six randomized controlled trials of systemic therapy met eligibility criteria. RECOMMENDATIONS Patients with newly diagnosed BC and BRCA1/ 2 mutations may be considered for breast-conserving therapy (BCT), with local control of the index cancer similar to that of noncarriers. The significant risk of a contralateral BC (CBC), especially in young women, and the higher risk of new cancers in the ipsilateral breast warrant discussion of bilateral mastectomy. Patients with mutations in moderate-risk genes should be offered BCT. For women with mutations in BRCA1/ 2 or moderate-penetrance genes who are eligible for mastectomy, nipple-sparing mastectomy is a reasonable approach. There is no evidence of increased toxicity or CBC events from radiation exposure in BRCA1/ 2 carriers. Radiation therapy should not be withheld in ATM carriers. For patients with germline TP53 mutations, mastectomy is advised; radiation therapy is contraindicated except in those with significant risk of locoregional recurrence. Platinum agents are recommended versus taxanes to treat advanced BC in BRCA carriers. In the adjuvant/neoadjuvant setting, data do not support the routine addition of platinum to anthracycline- and taxane-based chemotherapy. Poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and talazoparib) are preferable to nonplatinum single-agent chemotherapy for treatment of advanced BC in BRCA1/ 2 carriers. Data are insufficient to recommend PARP inhibitor use in the early setting or in moderate-penetrance carriers. Additional information available at www.asco.org/breast-cancer-guidelines .

BACKGROUND: Definitive local therapy of early stage breast cancer includes adjuvant radiotherapy after breast-conserving surgery (BCS). The authors analyzed factors that influence the receipt of radiotherapy therapy and their resultant impact on outcome. METHODS: Using data from the Kentucky Cancer Registry, the authors analyzed the rate of adjuvant radiotherapy for 11,914 women who underwent BCS as a primary surgical treatment for stage 0, I, or II breast cancer between 1998 and 2007. The authors assessed the probability of receiving radiotherapy by using multivariate logistic regression and measured impact on outcome by using Cox survival analysis. RESULTS: Overall, 66.2% of women received adjuvant radiotherapy for BCS over a 10-year period (annual rate range, 60.9%-70.1%). On multivariate analysis, the rate of receiving radiotherapy was drastically lower for women aged older than 70 years (vs younger) and rural Appalachian (vs non-Appalachian) populations. The rate was modestly lower for African American (vs white) women, those with in situ (vs invasive) disease, and uninsured (vs insured) patients. Lack of radiotherapy was associated with an increased hazard ratio for death of 1.67 (95% CI, 1.508-1.851) on Cox survival analysis when age, stage, tumor size, grade, hormone receptors, smoking, and insurance were factored into the analysis. The 10-year overall survival for patients who received adjuvant radiotherapy versus BCS alone was 79.7% versus 67.6% (P < .0001). CONCLUSIONS: Despite widespread knowledge of the benefit of RT after BCS, the rate of undertreatment remains high, with significant disparities for elderly, rural, minority, and uninsured women. Multidisciplinary management strategies, including accelerated and hypofractionated radiation regimens, are needed to eliminate disparities and improve outcomes.

First-line surgical options for early stage breast cancer and ductal carcinoma in situ include breast conserving surgery or mastectomy. We analyzed factors that influence the receipt of mastectomy and resultant trends over time. Registry analysis was carried out for 21,869 women who underwent up-front surgical treatment for stage 0, I or II breast cancer between 1998 and 2007 using data from the Kentucky Cancer Registry. We examined the trend of treatment over time and assessed the probability of receiving mastectomy using multivariate logistic regression. Overall, 54.5% of women received breast conservation and 45.5% received mastectomy over a 10-year period (annual BCS rate range: 46.9-61.2%). The overall mastectomy rate substantially decreased from 53.1% in 1998 to 38.8% in 2005 (p < 0.0001), but then increased to 45% in 2007 (p < 0.001). Between 2005 and 2007, the increase in mastectomies in the age groups of <50 years, 50-69 years, and ≥ 70 years was 7.5% (p = 0.0351), 4.9% (p = 0.0132) and, 8.0% (p = 0.0283), respectively. On multivariate analysis, the rate of receiving mastectomy was drastically higher for women with stage I or II (versus in situ) disease and moderate or poorly differentiated (versus well differentiated) histology. The rate was modestly higher for uninsured and government-insured (versus privately insured) patients, patients older than 70 years (versus younger), rural (versus urban) location, receptor negative (versus receptor positive) disease, and unusual histologies (versus ductal and lobular histology). There was no statistically significant difference in surgical choice with regard to race. Determinants of mastectomy for in situ and early stage breast cancer include stage, histology, age, insurance status, county of residence, receptor status. The rate of mastectomy declined until 2005 and is now increasing across all age groups, especially for women < 50 years and ≥ 70 years.

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In this longitudinal registry study, major independent determinants of mastectomy for early-stage breast cancer include year of diagnosis, insurance status, and stage. Mastectomy rates declined until 2004, but have since increased in conjunction with immediate reconstruction and contralateral prophylactic mastectomy. Additional study is needed to identify the underlying reasons for and unintended consequences of the reemergence of radical surgery for early-stage breast cancer in the era of multidisciplinary care.