Using emerging genomic information to create opportunities for targeted or risk-based screening in cancer prevention and control is a critical component of President Obama's Precision Medicine Initiative. But ?precision genomic screening? raises multiple ELSI (ethical, legal, social, and policy) concerns. The proposed ?embedded ELSI? research project presents a unique opportunity 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 Athena WISDOM study is a clinical trial (n=100K) that uses genomics to determine the appropriate use of mammography, and other forms of breast cancer screening, across the population. Breast cancer is among the most feared diseases; current screening technologies raise multiple anxieties, fueled by a high rate of false positive results. Recently funded by PCORI (the Patient Centered Outcomes Research Initiative) the WISDOM trial is significant because it is the first effort to target breast cancer screening according to individual genomic risk, as opposed to population characteristics. Based on a partnership with Color Genomics, the WISDOM trial creates a personalized risk score based on mutations in nine highly penetrant cancer genes (BRCA1/2, TP53, PTEN, STK11, CDH1, ATM, PALB2, CHEK2), as well as 157 SNP variants that are associated with increased risk. The final score also incorporates standard risk assessments such as family history and breast density. The proposed ELSI investigation builds on preliminary work conducted by investigators at UCSF's ?Center of Excellence in ELSI Research? who received a pilot award to create a multi-disciplinary research team; the team formed (a breast surgeon, an anthropologist/bioethicist, and a molecular pathologist) developed this proposal. Our collaborative project ?embeds? a comprehensive ELSI study within the Athena Breast Health Network's WISDOM study. The ELSI project has 4 specific aims. 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. 4) convene an Ethics Working Group that offers advice to WISDOM stakeholders in real time. Research across all the aims will be guided by an overarching theme: the intersection of precision genomics and known cancer health disparities. The outcomes of this project will inform the Precision Medicine Initiative, particularly efforts to improve cancer surveillance and early detection.
The proposed ELSI study (ethical, legal, social, and policy implications) will examine the risks, harms, benefits and challenges of a pioneering population-based precision genomic screening trial that aims to reduce the burden of breast cancer. Our study will provide a multifaceted, multilayered account of precision screening that identifies, analyzes and addresses ethical and social issues in the translation of genomic technology to clinical application.