ImportanceHalf of all carriers of inherited cancer-predisposing variants in BRCA1 and BRCA2 are male, but the implications for their health are underrecognized compared to female individuals. Germline variants in BRCA1 and BRCA2 (also known as pathogenic or likely pathogenic variants, referred to here as BRCA1/2 PVs) are well known to significantly increase the risk of breast and ovarian cancers in female carriers, and knowledge of BRCA1/2 PVs informs established cancer screening and options for risk reduction. While risks to male carriers of BRCA1/2 PVs are less characterized, there is convincing evidence of increased risk for prostate cancer, pancreatic cancer, and breast cancer in males. There has also been a rapid expansion of US Food and Drug Administration–approved targeted cancer therapies, including poly ADP ribose polymerase (PARP) inhibitors, for breast, pancreatic, and prostate cancers associated with BRCA1/2 PVs.ObservationsThis narrative review summarized the data that inform cancer risks, targeted cancer therapy options, and guidelines for early cancer detection. It also highlighted areas of emerging research and clinical trial opportunities for male BRCA1/2 PV carriers. These developments, along with the continued relevance to family cancer risk and reproductive options, have informed changes to guideline recommendations for genetic testing and strengthened the case for increased genetic testing for males.Conclusions and RelevanceDespite increasing clinical actionability for male carriers of BRCA1/2 PVs, far fewer males than female individuals undergo cancer genetic testing. Oncologists, internists, and primary care clinicians should be vigilant about offering appropriate genetic testing to males. Identifying more male carriers of BRCA1/2 PVs will maximize opportunities for cancer early detection, targeted risk management, and cancer treatment for males, along with facilitating opportunities for risk reduction and prevention in their family members, thereby decreasing the burden of hereditary cancer.

中文翻译：

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男性患者的 BRCA1、BRCA2 和相关癌症风险和管理


重要性BRCA1 和 BRCA2 中遗传性癌症易感变异的所有携带者中有一半是男性，但与女性个体相比，对他们健康的影响没有得到充分认识。众所周知，BRCA1 和 BRCA2 中的种系变异（也称为致病性或可能的致病性变异，此处称为 BRCA1/2 PV）会显著增加女性携带者患乳腺癌和卵巢癌的风险，了解 BRCA1/2 PV 为已建立的癌症筛查和降低风险的选择提供信息。虽然 BRCA1/2 PV 的男性携带者的风险不太明显，但有令人信服的证据表明男性患前列腺癌、胰腺癌和乳腺癌的风险增加。美国食品药品监督管理局批准的靶向癌症疗法也迅速扩大，包括聚 ADP 核糖聚合酶 （PARP） 抑制剂，用于治疗与 BRCA1/2 PV 相关的乳腺癌、胰腺癌和前列腺癌。它还强调了男性 BRCA1/2 PV 携带者的新兴研究和临床试验机会领域。这些发展，以及与家族癌症风险和生育选择的持续相关性，为基因检测指南建议的变化提供了信息，并加强了增加男性基因检测的理由。结论和相关性尽管 BRCA1/2 PVs 的男性携带者的临床可操作性不断提高，但接受癌症基因检测的男性个体远少于女性个体。肿瘤科医生、内科医生和初级保健临床医生应警惕地为男性提供适当的基因检测。 识别更多 BRCA1/2 PV 的男性携带者将最大限度地提高男性癌症早期发现、有针对性的风险管理和癌症治疗的机会，同时促进其家庭成员降低和预防风险的机会，从而减轻遗传性癌症的负担。