Yadav Siddhartha, Couch Fergus J
1 Department of Oncology, Mayo Clinic, Rochester, MN.
2 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Am Soc Clin Oncol Educ Book. 2019 Jan;39:61-74. doi: 10.1200/EDBK_238987. Epub 2019 May 17.
The field of germline genetic testing for breast cancer (BC) risk has evolved substantially in the last decade. The introduction of multigene panel testing (MGPT) led to an urgent need to understand the cancer risk associated with several genes included in the panels. Although the research on understanding the cancer risk associated with mutations in several genes continues, there is also a need to understand the modifying effects of race and ethnicity, family history, and BC pathology on the prevalence of germline mutations and associated BC risk. Furthermore, polygenic risk scores (PRSs) to predict BC risk in patients with or without germline mutations in cancer-predisposition genes are now available for clinical use, although data on the clinical utility of PRSs are lacking. In patients with advanced BC associated with mutation, olaparib and talazoparib are now approved for treatment. In addition, molecular profiling studies are being used to clarify the BC tumor biology in mutation carriers to identify potential therapeutic options. In this article, we discuss these advances in the field of germline genetic testing and highlight current limitations and implications for clinical care.
在过去十年中，乳腺癌（BC）风险的种系基因检测领域有了显著发展。多基因panel检测（MGPT）的引入导致迫切需要了解该检测panel中包含的多个基因相关的癌症风险。尽管关于了解多个基因中突变相关癌症风险的研究仍在继续，但也有必要了解种族、家族史和BC病理对种系突变患病率及相关BC风险的修饰作用。此外，现在已有多基因风险评分（PRSs）可用于临床，以预测癌症易感基因中有或没有种系突变的患者的BC风险，尽管缺乏关于PRSs临床效用的数据。在携带特定突变的晚期BC患者中，奥拉帕利和他拉唑帕利现已获批用于治疗。此外，分子谱分析研究正被用于阐明突变携带者的BC肿瘤生物学，以确定潜在的治疗选择。在本文中，我们讨论种系基因检测领域的这些进展，并强调当前的局限性以及对临床护理的影响。
