BRCA1 和/或 BRCA2 基因 (BRCAm) 突变会增加患乳腺癌 (BC) 的风险，并且在约 5% 的未经选择的乳腺癌患者中发现突变。由种系 BRCAm (gBRCAm) 引起的 BC 具有独特的临床特征，并且对 DNA 损伤剂（例如聚（ADP-核糖）聚合酶 (PARP) 抑制剂和铂类化疗）的敏感性增加，并且对细胞周期蛋白依赖性激酶的敏感性可能降低4 和 6 (CDK4/6) 抑制剂。鉴于早期和晚期疾病中 gBRCAm BC 的治疗前景不断变化，及时确定 gBRCAm 状态对于促进为患者制定最有效的治疗策略至关重要。然而，由于转诊率不理想和/或基因检测采用率低，许多 gBRCAm 患者未被识别。我们讨论了早期和晚期 BC 环境中 gBRCAm 患者对治疗的不同反应的当前证据，包括 PARP 抑制剂、铂类化疗和 CDK4/6 抑制剂的结果，以及正在进行的治疗创新和这些治疗的潜力接近。还审查了当前的基因检测策略，包括关于谁和何时检测 gBRCAm 的最新指南，以及检测面临的挑战以及如何克服这些挑战。© 2024。作者。

Mutations in the BRCA1 and/or BRCA2 genes (BRCAm) increase the risk of developing breast cancer (BC) and are found in ~5% of unselected patients with the disease. BC resulting from a germline BRCAm (gBRCAm) has distinct clinical characteristics along with increased sensitivity to DNA-damaging agents such as poly(ADP-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapies, and potentially decreased sensitivity to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. Given the evolving treatment landscape for gBRCAm BC in early and advanced disease settings, timely determination of gBRCAm status is fundamental to facilitate the most effective treatment strategy for patients. However, many patients with gBRCAm are not identified due to suboptimal referral rates and/or a low uptake of genetic testing. We discuss current evidence for a differential response to treatment in patients with gBRCAm in early and advanced BC settings, including outcomes with PARP inhibitors, platinum-based chemotherapies, and CDK4/6 inhibitors, as well as ongoing treatment innovations and the potential of these treatment approaches. Current genetic testing strategies are also examined, including the latest guidelines on who and when to test for gBRCAm, as well as challenges to testing and how these may be overcome.© 2024. The Author(s).