Cancer survivors harboring inherited pathogenic variants in the breast cancer (BC) susceptibility genes BRCA1 or BRCA2 are at increased risk of ovarian cancer (OC) and also of contralateral BC. For these women, risk-reducing surgery (RRS) may contribute to risk management. However, women with locally advanced or metastatic breast cancer (ABC) were excluded from clinical trials evaluating the benefit of these procedures in the BRCA1/2 carriers, and thus, current guidelines do not recommend RRS in this specific setting. Although ABC remains an incurable disease, recent advances in treatment have led to increased survival, which, together with improvement in RRS techniques, raise questions about the potential role of RRS in the management of BRCA1/2 ABC patients. When should RRS be discussed as an option for BRCA1/2 patients diagnosed with ABC? To address this issue, we report two clinical cases that reflect new challenges in routine oncology practice. Team experience and patient motivations may shape multidisciplinary decisions in the absence of evidence-based data. A wise rationale may be the analysis of the competing risks of death by a previous ABC against risk of death by a secondary BC or OC, tailored to patient preferences.

中文翻译：

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BRCA1/2晚期乳腺癌患者降低风险手术的挑战和思考

在乳腺癌 (BC) 易感基因 BRCA1 或 BRCA2 中携带遗传致病变异的癌症幸存者患卵巢癌 (OC) 和对侧 BC 的风险增加。对于这些女性，降低风险手术 (RRS) 可能有助于风险管理。然而，局部晚期或转移性乳腺癌 (ABC) 的女性被排除在评估这些手术对 BRCA1/2 携带者的益处的临床试验之外，因此，目前的指南不推荐在这种特定情况下进行 RRS。尽管 ABC 仍然是一种无法治愈的疾病，但最近治疗方面的进步已经提高了生存率，再加上 RRS 技术的改进，引发了关于 RRS 在 BRCA1/2 ABC 患者管理中的潜在作用的问题。何时应讨论 RRS 作为诊断为 ABC 的 BRCA1/2 患者的一种选择？为了解决这个问题，我们报告了两个临床案例，这些案例反映了常规肿瘤学实践中的新挑战。在缺乏循证数据的情况下，团队经验和患者动机可能会影响多学科决策。一个明智的理由可能是分析先前 ABC 的死亡风险与继发性 BC 或 OC 的死亡风险的竞争风险，根据患者的喜好量身定制。