Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients

PURPOSE: The prevalence of mutations in cancer susceptibility genes such as BRCA1 and BRCA2 and other cancer susceptibility genes and their clinical relevance are largely unknown among a large series of unselected breast cancer patients in Chinese population. <p> </p> <p>METHODS: A total of 8085 consecutive unselected Chinese breast cancer patients were enrolled. Germline mutations in 46 cancer susceptibility genes were detected using a 62-gene panel.</p> <p> </p> <p>RESULTS: Pathogenic mutations were identified in 9.2% of patients among the 8085 unselected breast cancer patients .Of these, 5.3% of patients carried a BRCA1 or BRCA2 mutation (1.8% in BRCA1 and 3.5% in BRCA2), 2.9% carried other breast cancer susceptibility genes (BOCG), and 1.0% carried another cancer susceptibility genes. Triple-negative breast cancers had the highest prevalence of BRCA1/2 mutations (11.2%) and other BOCG mutations (3.8%) among the four molecular subgroups, whereas ER-/PR-HER2+ breast cancers had the lowest mutations in BRCA1/2 (1.8%) and BOCG (1.6%). In addition, BRCA1 mutation carriers had a significant worse disease-free survival [unadjusted hazard ratio (HR) 1.60; 95% confidence interval (CI) 1.10-2.34; p=0.014) and disease-specific survival (unadjusted HR 1.96; 95% CI, 1.03-3.65; p=0.040) than did non-carriers; whereas no significant difference in survival was found between BRCA2 mutation carriers and non-carriers.</p> <p> </p> <p>CONCLUSIONS: 9.2% of breast cancer patients carry a pathogenic mutation in cancer susceptibility genes in this large unselected series. Triple-negative breast cancers have the highest prevalence of mutations in BRCA1 /2 and other breast cancer susceptibility genes among the four molecular subgroups, whereas ER-/PR-HER2+ breast cancers had the lowest mutations in these genes.

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