Abstract PD5-10: Mutational burden of the normal breast during age and pregnancy

Background: The potential for accumulation of somatic mutations in the healthy breast throughout life and pregnancy is poorly understood. In particular, the unique mutational landscape of both epithelial and stromal components of the mammary gland has not been investigated in depth. As cancer risk correlates with both age, age of first-time pregnancy and other factors including pregnancy itself, we wished to study mutational rate over time, using these landmarks. Methods: Here, using whole genome sequencing, we determined how the rate of mutations in both cancer drivers and passenger mutations are affected by both age and pregnancy. We aimed to describe for the first time how the mammary epithelium and stroma differ in their mutational burden. Results: Our analysis of epithelial and stromal laser-capture micro-dissected DNA from 25 normal breast samples of nulliparous and age-matched early- and late-parous women collected from Komen Tissue Bank, University of Indiana, shows that the mammary gland is characterised by known COSMIC signatures SBS1 and SBS5, both of which correlate with age (p Citation Format: Biancastella Cereser, Neha Tabassum, Lisa Del Bel Belluz, Sladjana Zagorac, Angela Yiu, Philip Carter, Cristian Miere, Alicia R Jeffries-Jones, Justin Stebbing. Mutational burden of the normal breast during age and pregnancy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD5-10.