Abstract CS1-3: Moderate penetrance mutations: What to do?

Abstract

Abstract Genetic testing for breast and ovarian cancer susceptibility has expanded beyond sequencing of BRCA1 and BRCA2. Panel testing has allowed for rapid, affordable, and routine testing of multiple genes simultaneously. There is no one standard “panel” – panels range in types and number of genes tested and panel composition is at the discretion of the ordering provider. Some of the genes commonly included have been long associated with specific genetic syndromes with high lifetime risks of the associated cancers, e.g. mutations in PTEN and Cowden's Syndrome, TP53 and Li Fraumeni Syndrome, STK11 and Peutz-Jeghers Syndrome, and CHD1 and Hereditary Diffuse Gastric Cancer. The inclusion of these “high penetrance genes” on broad cancer panels can lead to challenges regarding discussion and management when detected in families which are not syndromic (for example, the discussion of prophylactic gastrectomy in individuals with CDH1 mutations and no family history of gastric cancer). Mutations in other genes are clearly associated with breast cancer but with lower lifetime risks than for BRCA1 and BRCA2; for example, the lifetime risk of breast cancer for a PALB2 mutation is approximately 40-50%, whereas for ATM and truncating CHEK2 mutations this risk is 25-30%. Mutations in BRIP, RAD51C, and RAD51D are clearly associated with ovarian cancer with lifetime risks of approximately 10% (significantly lower than for BRCA1 mutations). This lecture will address the current understanding of associated cancer risks for mutations in genes included in hereditary cancer panels with a focus on implications for risk reduction and treatment. Citation Format: Domchek S. Moderate penetrance mutations: What to do? [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 CS1-3.