Abstract P5-09-18: Multiple cancer susceptible genes sequencing in BRCA-negative breast cancers with high hereditary risk

Abstract

Abstract Background Breast cancer susceptibility is strongly associated with a patient's hereditary background. Comprehensive BRCA mutation screening in our cancer center shows a lower BRCA mutation prevalence (9.1%) in Chinese breast cancer patients with hereditary risk. Multiple cancer susceptible genes sequencing can assist in discovering detrimental germline mutation in BRCA-negative breast cancers. Methods From 2005-2014, BRCA-negative breast cancer patients with any two of the following risk factors were recruited: (1) pathological diagnosis of triple-negative breast cancer, (2) male breast cancer, (3) primary bilateral breast cancers in one individual, regardless of synchrony or asynchrony, (4) early-age onset breast cancer (less than or equal to 40 years of age at diagnosis), or (5) patients with a family history of breast and/or ovarian cancer (at least one first- and/or second-degree relative with breast cancer or ovarian cancer). A total of 384 Chinese subjects were screened by next-generation sequencing for 32 breast cancer associated susceptibility genes (APC, ATM, BARD1, BMPR1A, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, MEN1, MET, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PALLD, PMS2, PTCH1, PTEN, RAD50, RAD51C, RAD51D, RET, SMAD4, STK11, TP53, VHL). Mutations were classified as pathogenic/likely-pathogenic if they had a truncating, initiation codon or splice donor/acceptor effect, or if pathogenicity was demonstrated in published literature. Results In total, we acquired 39 patients (10.2%) with pathogenic/likely-pathogenic germline mutations, including one carrying two distinct mutations. Major mutant non-BRCA genes were MUTYH (n=11), PTCH1 (n=7), RET (n=6) and PALB2 (n=5). Other mutant genes included TP53 (n=3), RAD51D (n=2), CHEK2 (n=1), BRIP1 (n=1), CDH1 (n=1), MRE11 (n=1), RAD50 (n=1) and PALLD (n=1). In addition, PTCH1 mutation carriers were found to be associated with the clinical features of triple-negative and early-age onset breast cancer. Conclusions Among BRCA-negative breast cancer patients with high hereditary risk in China, 10.2% carried mutations in breast cancer associated susceptibility genes. MUTYH and PTCH1 had relatively high mutation rates (2.9% and 1.8%). Some clinical features might be associated with germline mutations of particular genes in breast cancer. Key words germline mutation, BRCA-negative, hereditary breast cancer, multiple-gene sequencing Citation Format: Lang G-T, Hu X, Shi J-X, Huang W, Shao Z-M. Multiple cancer susceptible genes sequencing in BRCA-negative breast cancers with high hereditary risk [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-09-18.