Abstract MS1-1: Characterising cancer risks for carriers of mutations in BRCA1, BRCA2, PALB2, and RAD51C genes

Abstract

Abstract The presentation will provide an overview of the latest developments and challenges in understanding the penetrance of mutations in the BRCA1, BRCA2, PALB2 and RAD51C genes. Genetic counselling currently relies on average cancer risk estimates obtained from retrospective penetrance studies involving large numbers of families segregating mutations in these genes. The talk will present penetrance estimates from ongoing prospective analyses, based on data from the International BRCA1/2 Carrier Cohort Study, the largest cohort of BRCA1/2 mutation carriers worldwide that includes >10,000 mutation carriers at baseline with prospective follow-up information. Several common alleles and other risk factors have now been shown to modify breast cancer risk for BRCA1 and BRCA2 mutation carriers. The talk will review the latest efforts and results from the Consortium of Investigators of Modifiers of BRCA1/2 to identify genetic modifiers of risk and provide individualised cancer risks for BRCA1 and BRCA2 mutation carriers on the basis of polygenic risk scores. We will also present penetrance estimates based on analyses of combined data from families segregating mutations in PALB2 and RAD51C, the largest efforts of their kind. Finally the presentation will demonstrate how the effects of common and rare breast cancer susceptibility variants are incorporated into the BOADICEA model to provide comprehensive risks of developing breast cancer in the future. Citation Format: Antonis C. Antoniou. Characterising cancer risks for carriers of mutations in BRCA1, BRCA2, PALB2, and RAD51C genes [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr MS1-1.