Personalized medicine and population-based genomic screening are at the forefront of a new approach to disease prevention. However, “precision genomic screening” raises multiple ELSI (ethical, legal, social, and policy) concerns. The purpose of the project, led by Barbara Koenig, PhD, and Galen Joseph, PhD, is to follow and assess the ELSI issues that accompany a pioneering randomized pragmatic clinical trial of a risk-based approach to breast cancer screening. The WISDOM (Women Informed to Screen Depending on Measures of Risk) study is a clinical trial that uses genomics to determine the appropriate use of mammography, and other forms of breast cancer screening, across the population. The trial compares annual mammography to a “personalized” approach to screening, using factors like age, race, family history and health history combined with genetic testing to offer a recommendation for the frequency and type of breast cancer screening a woman should have. Our study “embeds” a comprehensive ELSI project within the trial. We seek to: 1) examine how ELSI concerns are addressed throughout the implementation of the WISDOM trial via ethnography and key informant interviews with stakeholders; 2) elucidate the experience and meanings of risk-based screening for trial participants and their primary care providers (PCPs) via qualitative interviews with women stratified by risk level, focus groups with PCPs, and a survey of the full trial cohort; 3) explore the consequences of receiving a positive result for one of the nine high penetrance cancer susceptibility genes via observations of genetic counseling sessions, qualitative interviews at two time points, a survey, and focus groups with WISDOM study breast health specialists; and 4) convene an Ethics Working Group that offers advice to WISDOM stakeholders in real time. Our study will run from January 2017 to December 2021 and is funded by the National Cancer Institute.