Abstract P6-06-06: Comprehensive analysis of BRCA (BRCAm) and other germline mutations (GRm) with a clinicopathological association in breast cancer: An Indian study

Background: BRCAm and other GRm testing using next generation sequencing (NGS) in early diagnosed and/or metastatic breast cancer (BC) helps in the identification of both unambiguously defined deleterious mutations and sequence variants of unknown clinical significance (VUS). The early detection of these mutations in the proband and the family members help in risk stratification and instituting effective monitoring, surveillance and disease management strategies. Methods: Out of total 200 patients diagnosed with BC (April 2013-15) 77 unrelated individuals were consented to be profiled by NGS on MiSeq platform using TruSight Cancer panel (consisting of 94 genes including 13 genes highly associated with risk of inherited breast and/or ovarian cancer) in an IRB-approved prospective study in a CLIA compliant laboratory. Paired end sequencing was done with an average coverage of > 450X. Data was processed using STRAND software and interpreted using "Strand Omics" platform. The paired tumor samples were analysed for pathological stage, histological type and hormonal status. Results: GRm were detected in 61 cases (79%). Among all mutations detected, BRCA1/2 were found in 51% (31% in BRCA1, 20% in BRCA2) of cases. BRCA1 was found to be co-mutated with BRCA2 in 2 cases. Out of 37 deleterious mutations in BRCA1/2 genes only 10 were reported to be pathogenic (6 in BRCA1 and 4 in BRCA2) and rest were VUS. Mutation frequencies were higher among high grade IDC with HER2-ve tumors including TNBC (53%, p Conclusions: Our study in a small cohort clearly highlighted the significance of germline testing and classifying the variant in larger cohort of BC patients with a strong family Hx of cancer particularly in BRCA1/2 positive families , and in women Citation Format: Ghosh M, ML S, Upasana M, Chodhury S, Mannan AU, Southekal S, Manjima C, Patil S, Murugan K, Mahesh B, Nayak R, Sridhar PSS, Rao N, Krishnamoorthy N, Gupta V, Satheesh CT, Subramanian K, Ajaikumar BS. Comprehensive analysis of BRCA (BRCAm) and other germline mutations (GRm) with a clinicopathological association in breast cancer: An Indian study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-06-06.