Abstract IA05: Modeling genetic susceptibility to breast cancer

Several breast cancer genetic susceptibility variants have been identified to date. These include mutations in the high risk BRCA1 and BRCA2 genes, other rare genetic variants conferring intermediate to high risks (e.g. PALB2, CHEK2, ATM and others) and >150 common alleles (SNPs) conferring low risks. The presentation will provide an overview of the latest developments and challenges in understanding the penetrance of mutations in BRCA1, BRCA2 and PALB2. Genetic counseling of women with BRCA1 and BRCA2 mutations currently relies on average cancer risk estimates obtained from retrospective penetrance studies. The talk will present penetrance estimates from ongoing prospective analyses, based on data from the International BRCA1/2 Carrier Cohort Study, the largest prospective cohort of BRCA1/2 mutation carriers that includes ~10,000 BRCA1/2 mutation carriers with follow-up information. The talk will also review the latest efforts and results from the Consortium of Investigators of Modifiers of BRCA1/2 to identify and characterise genetic modifiers of cancer risks for BRCA1 and BRCA2 mutation carriers and to provide individualized cancer risks for women with BRCA1 and BRCA2 mutations. Finally, the presentation will describe the efforts to develop a comprehensive risk prediction model for breast cancer, specifically the BOADICEA model that includes the explicit effects of mutations in BRCA1, BRCA2, PALB2, CHEK2, ATM, and of the common breast cancer susceptibility variants identified through genome-wide association studies. Citation Format: Antonis C. Antoniou. Modeling genetic susceptibility to breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr IA05.