Hahnen Eric, Hauke Jan, Engel Christoph, Neidhardt Guido, Rhiem Kerstin, Schmutzler Rita K
Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Breast Care (Basel). 2017 Mar;12(1):15-19. doi: 10.1159/000455999. Epub 2017 Feb 24.
Triple-negative breast cancer (TNBC) is associated with a poor prognosis and defines a subgroup of patients who do not benefit from endocrine or anti-HER2 therapy. Rather than being a biological entity, TNBC represents a heterogeneous disease, and further subtyping is necessary to establish targeted therapies. Germline mutational status may serve as a robust biomarker predicting therapy response, especially with respect to compounds challenging the DNA repair machinery. Patients with TNBC usually show an early onset of the disease, as well as a positive family history of breast and/or ovarian cancer in more than one third of all cases, which suggests that TNBC is closely associated with a hereditary disease cause. In unselected TNBC cases, the prevalence of pathogenic germline mutations is approximately twice as high as in breast cancer overall. Early age at diagnosis and positive family history are strong predictors for an increased mutation probability, which is up to 40% when both risk factors are considered. Apart from , the rarely mutated breast cancer predisposition genes and have been associated with TNBC. This review summarizes the role of germline mutational status in TNBC pathogenesis. Clinical trials addressing mutation carriers are discussed.
三阴性乳腺癌（TNBC）预后较差，这类患者无法从内分泌治疗或抗HER2治疗中获益。TNBC并非一种生物学实体，而是一种异质性疾病，因此需要进一步细分以确定靶向治疗方案。胚系突变状态可能是预测治疗反应的可靠生物标志物，尤其是对于那些作用于DNA修复机制的化合物而言。TNBC患者通常发病较早，超过三分之一的病例有乳腺癌和/或卵巢癌的家族史，这表明TNBC与遗传性病因密切相关。在未经筛选的TNBC病例中，胚系致病突变的发生率约为总体乳腺癌的两倍。诊断时年龄较小和家族史阳性是突变概率增加的有力预测因素，若同时考虑这两个风险因素，突变概率可达40%。除了 ，很少发生突变的乳腺癌易感基因 和 也与TNBC有关。本综述总结了胚系突变状态在TNBC发病机制中的作用，并讨论了针对 突变携带者的临床试验。
