Fujii Takaaki
Department of Breast Surgery and Oncology, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai, Chiba, 270-1694, Japan.
Int J Clin Oncol. 2025 Aug 17. doi: 10.1007/s10147-025-02853-8.
Hereditary breast and ovarian cancer (HBOC) syndrome is caused by germline mutations in the BRCA1 and BRCA2 genes, which play critical roles in DNA double-strand break repair. Pathogenic variants (PVs) in these genes lead to homologous recombination deficiency (HRD), genomic instability, and increased cancer risk. BRCA1-associated breast cancers are predominantly triple-negative breast cancer (TNBC) with aggressive behavior, and BRCA2-mutated cases are mostly hormone receptor-positive and share similarities with sporadic luminal tumors. Genetic testing for BRCA PVs is crucial for identifying at-risk individuals and enabling risk-reducing interventions and personalized treatment strategies. In this review, we discuss the carcinogenic form and characteristics of BRCA PV-carrier breast cancer, focusing on BRCA-associated hereditary breast cancer and addressing its clinical characteristics and molecular mechanisms. Personalized treatment approaches that integrate patients' BRCA status with their tumor biology are essential for optimizing patient outcomes.
遗传性乳腺癌和卵巢癌（HBOC）综合征由BRCA1和BRCA2基因的种系突变引起，这两个基因在DNA双链断裂修复中起关键作用。这些基因中的致病变异（PVs）会导致同源重组缺陷（HRD）、基因组不稳定，并增加患癌风险。与BRCA1相关的乳腺癌主要是具有侵袭性的三阴性乳腺癌（TNBC），而BRCA2突变的病例大多为激素受体阳性，与散发性管腔型肿瘤有相似之处。对BRCA PVs进行基因检测对于识别高危个体、实施降低风险的干预措施以及制定个性化治疗策略至关重要。在本综述中，我们讨论了携带BRCA PVs的乳腺癌的致癌形式和特征，重点关注与BRCA相关的遗传性乳腺癌，并阐述其临床特征和分子机制。将患者的BRCA状态与其肿瘤生物学相结合的个性化治疗方法对于优化患者治疗效果至关重要。
