Department of Breast Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Int J Mol Sci. 2022 Jul 5;23(13):7481. doi: 10.3390/ijms23137481.
Approximately 5-10% of all breast cancer (BC) cases are caused by germline pathogenic variants (GPVs) in various cancer predisposition genes (CPGs). The most common contributors to hereditary BC are and , which are associated with hereditary breast and ovarian cancer (HBOC). , , , , , and have also been recognized as CPGs with a high to moderate risk of BC. Primary and secondary cancer prevention strategies have been established for HBOC patients; however, optimal preventive strategies for most hereditary BCs have not yet been established. Most BC-associated CPGs participate in DNA damage repair pathways and cell cycle checkpoint mechanisms, and function jointly in such cascades; therefore, a fundamental understanding of the disease drivers in such cascades can facilitate the accurate estimation of the genetic risk of developing BC and the selection of appropriate preventive and therapeutic strategies to manage hereditary BCs. Herein, we review the functions of key BC-associated CPGs and strategies for the clinical management in individuals harboring the GPVs of such genes.
约 5-10%的乳腺癌（BC）病例是由各种癌症易感基因（CPGs）中的种系致病性变异（GPVs）引起的。导致遗传性 BC 的最常见因素是 和 ，它们与遗传性乳腺癌和卵巢癌（HBOC）有关。 、 、 、 、 和 也被认为是具有高到中度 BC 风险的 CPGs。已经为 HBOC 患者建立了一级和二级癌症预防策略；然而，大多数遗传性 BC 的最佳预防策略尚未建立。大多数与 BC 相关的 CPGs 参与 DNA 损伤修复途径和细胞周期检查点机制，并在这些级联中共同发挥作用；因此，对这些级联中疾病驱动因素的深入了解有助于准确估计发生 BC 的遗传风险，并选择适当的预防和治疗策略来管理遗传性 BC。在此，我们综述了关键的 BC 相关 CPGs 的功能以及携带这些基因的 GPVs 的个体的临床管理策略。
