Grant Number:	5R21CA194965-02 Interpret this number
Primary Investigator:	Schwartz, Marc
Organization:	Georgetown University
Project Title:	Evolving Model of Cancer Susceptibility Testing: Clinical Decisions & Outcomes
Fiscal Year:	2017

 DESCRIPTION (provided by applicant): Genetic counseling and testing for BRCA1 and BRCA2 (BRCA) is standard care for women at risk for hereditary breast/ovarian cancer (HBOC). Yet most women who undergo such testing receive an uninformative negative result, providing little insight into their cancer risks. However, recent advances in next-generation sequencing (NGS) technology now allow the simultaneous testing of BRCA along with multiple additional HBOC susceptibility genes at a cost comparable to or less than the previous cost of BRCA testing alone. Although these panels were initially targeted to women who had previously received uninformative BRCA test results, the 2013 Supreme Court decision invalidating the BRCA patents led to a paradigm shift in which multigene panels are now regularly used as a first-line clinical test for HBOC. Beyond the BRCA genes, widely used commercial panels test for mutations in several highly penetrant and clinically actionable cancer susceptibility genes. There are also widely used 'extended panels' that include genes of moderate penetrance for which evidence-based medical management guidelines are absent. The high analytic validity and ability of these panels to cost-effectively detect mutations aside from BRCA has led to rapid adoption in many centers and routine reimbursement by insurers. However, concerns remain about the routine clinical use of extended panels. These concerns center on the potential increase in clinical uncertainty due to questionable clinical utility, the lack of management guidelines for many of the genes in the extended panels, the greatly increased identification of variants of uncertain clinical significance (VUS), and the absence of patient outcome data to inform clinical guidelines and new genetic counseling approaches. Despite these unanswered questions, extended panels are rapidly supplanting single gene testing. At present, virtually nothing is known about how patients interact with these tests and how results impact risk management and psychosocial outcomes. Guided by work on clinical uncertainty and Baum's model of Stress and Genetic Testing, we will address this knowledge gap with a longitudinal study to assess patient decisions and psychological outcomes related to clinical multigene panel testing for HBOC. We will also examine what clinical, sociodemographic, and patient factors predict test choice. We will prospectively enroll 468 women referred for clinical HBOC genetic counseling and testing. Such counseling encompasses shared decision making to help patients make informed decisions about genetic testing choice (i.e., BRCA/high risk panel versus extended panel). Participants will complete a baseline interview and follow-up surveys after pre- and post-test genetic counseling, and 6-months after test result disclosure. This study will move the field forward by informing our understanding of the use of extended gene panels in clinical care. We will reach a population of high-risk women receiving testing in routine care and assess real-world clinical outcomes.





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