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.

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遗传性乳腺癌的管理：美国临床肿瘤学会、美国放射肿瘤学会和外科肿瘤学会指南

目的 为具有 BC 易感基因种系突变的乳腺癌 (BC) 患者的管理制定建议。方法 美国临床肿瘤学会、美国放射肿瘤学会和外科肿瘤学会召集了一个专家小组，根据对文献的系统回顾和正式的共识过程制定建议。结果 58 篇文章符合纳入标准，构成了当地治疗推荐的证据基础；六项全身治疗的随机对照试验符合资格标准。建议 新诊断的 BC 和 BRCA1/2 突变患者可以考虑进行保乳治疗 (BCT)，对指示癌症的局部控制与非携带者相似。对侧 BC (CBC) 的重大风险，特别是在年轻女性中，同侧乳房新发癌症的风险较高，值得讨论双侧乳房切除术。中危基因突变的患者应接受 BCT。对于符合乳房切除术条件的 BRCA1/2 或中等外显基因突变的女性，保留乳头的乳房切除术是一种合理的方法。没有证据表明 BRCA1/2 携带者的辐射暴露会增加毒性或 CBC 事件。ATM 携带者不应拒绝接受放射治疗。对于生殖系 TP53 突变的患者，建议进行乳房切除术；放射治疗是禁忌的，除非那些有显着局部复发风险的患者。与紫杉烷相比，推荐使用铂类药物治疗 BRCA 携带者的晚期 BC。在辅助/新辅助设置中，数据不支持在基于蒽环类和紫杉类的化疗中常规添加铂。聚（ADP-核糖）聚合酶（PARP）抑制剂（olaparib 和 talazoparib）在治疗 BRCA1/2 携带者晚期 BC 时优于非铂单药化疗。数据不足以推荐在早期环境或中等外显率携带者中使用 PARP 抑制剂。如需更多信息，请访问 www.asco.org/breast-cancer-guidelines。