ELSIcon2022 Paper: Returning Polygenic Risk Scores to Participants in a Pragmatic Clinical Trial of Breast Cancer Screening: Ethical Dilemmas and Participant (mis)Understanding

ELSIcon2022 • Paper • June 3, 2022

Jennifer James, Leslie Riddle, Mika Caruncho, Barbara Koenig, Galen Joseph

Population-based genomic screening is at the forefront of a new approach to disease prevention. While panel testing for highly penetrant genetic variants is increasingly used to assess cancer risk, the personal and clinical utility of Polygenic Risk Scores (PRS), algorithms that sum the influence of multiple small genetic variations, has yet to be established. Our embedded ELSI study of the WISDOM Trial, a pragmatic RCT that utilizes genomics and other factors to test a “risk-stratified” approach to breast cancer screening, seeks to elucidate key ethical and social questions about this approach. This presentation describes WISDOM’s implementation of PRS, focusing on decisions about risk communication. How is uncertainty conveyed? While in the original trial design PRS results were not meant to be disclosed to participants, WISDOM has moved towards returning PRS, raising questions about how PRS risk numbers can or should be understood, interpreted, and utilized by participants at both high and low risk for breast cancer. We will discuss findings from qualitative interviews with these participants and analyses of their results disclosure sessions to explore key ethical dilemmas, such as how participants (mis)understand the experimental nature of PRS and how that (mis)understanding may shape their screening decisions. Despite limited data on its clinical utility, uncertain insurance coverage and limited provider knowledge about the novel technology, PRS is increasingly used in clinical and commercial contexts to guide screening recommendations. This presentation offers insights into the ethical translation of implementing PRS during this liminal phase of its development.