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

Abstract

<b>Purpose:</b> The prevalence of mutations in cancer susceptibility genes such as <i>BRCA1</i> and <i>BRCA2</i> and other cancer susceptibility genes and their clinical relevance are largely unknown among a large series of unselected breast cancer patients in the Chinese population.<b>Experimental Design:</b> A total of 8,085 consecutive unselected Chinese breast cancer patients were enrolled. Germline mutations in 46 cancer susceptibility genes were detected using a 62-gene panel.<b>Results:</b> Pathogenic mutations were identified in 9.2% of patients among the 8,085 unselected breast cancer patients. Of these, 5.3% of patients carried a <i>BRCA1</i> or <i>BRCA2</i> mutation (1.8% in <i>BRCA1</i> and 3.5% in <i>BRCA2</i>), 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 <i>BRCA1/2</i> 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 <i>BRCA1/2</i> (1.8%) and BOCG (1.6%). In addition, <i>BRCA1</i> mutation carriers had a significant worse disease-free survival [unadjusted hazard ratio (HR) 1.60; 95% confidence interval (CI) 1.10-2.34; <i>P</i> = 0.014] and disease-specific survival (unadjusted HR 1.96; 95% CI, 1.03-3.65; <i>P</i> = 0.040) than did non-carriers, whereas no significant difference in survival was found between <i>BRCA2</i> mutation carriers and non-carriers.<b>Conclusions:</b> 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 <i>BRCA1 /2</i> and other breast cancer susceptibility genes among the four molecular subgroups, whereas ER^-/PR^-HER2⁺ breast cancers had the lowest mutations in these genes. <i>Clin Cancer Res; 23(20); 6113-9. ©2017 AACR</i>.