||5R01CA211999-05 Interpret this number
||University Of California, San Francisco
||Precision Genomics in the Wisdom Pragmatic Clinical Trial: an "Embedded" ELSI Study of Risk-Based Breast Cancer Screening
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.
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