摘要Objective: Approximately 5％–10％ of breast cancer (BC) patients display familial traits that are genetically inherited among the members of a family. The purpose of this study was to profile the germline mutations in 43 genes with different penetration rates and their correlations with phenotypic traits in Chinese familial BC families.Methods: Ion Torrent S5?-based next generation sequencing was conducted on 116 subjects from 27 Chinese familial BC families. Results: Eighty-one germline mutations in 27 BC predisposition genes were identified in 82.8％ (96/116) of the cases. Among these, 80.8％ of the mutated genes were related to DNA damage repair. Fourteen possible disease-causing variants were identified in 13 of 27 BC families. Only 25.9％ (7/27) of the BC families exhibited hereditary deficiency in BRCA1/2 genes, while 22.2％ of the BC families exhibited defects in non-BRCA genes. In all, 41.7％ (40/96) of the mutation carriers had BRCA mutations, 88.5％ (85/96) had non-BRCA mutations, and 30.2％ (29/96) had both BRCA and non-BRCA mutations. The BC patients with BRCA mutations had a higher risk of axillary lymph node metastases than those without mutations (P < 0.05). However, the BC patients with non-BRCA mutations frequently had a higher occurrence of benign breast diseases than those without mutations (P < 0.05). Conclusions: In addition to BRCA1/2, genetic variants in non-BRCA DNA repair genes might play significant roles in the development of familial/hereditary BC. Therefore, profiling of multiple BC predisposition genes should be more valuable for screening potential pathogenic germline mutations in Chinese familial/hereditary BC.