PROJECT SUMMARY Among the estimated one million Americans who have screened positive for specific genetic variants related to Hereditary Breast and Ovarian Cancer Syndrome (HBOC) or Lynch Syndrome (LS), less than half are up to date on evidence-based cancer prevention measures that may increase early detection of syndrome-related cancers or prevent these cancers altogether. Most patients newly diagnosed with hereditary cancer syndromes receive extensive initial care from genetic counselors or oncology teams but for many patients without a cancer diagnosis at the time of syndrome identification, access to regular follow-up care from oncologists and genetic counselors is limited. Pilot data show that the most frequent source of care for patients with HBOC or LS is the primary care setting, but many primary care clinicians are unfamiliar with rapidly evolving cancer prevention guidelines for patients with HBOC or LS. Although primary care clinicians are ideally positioned to make timely referrals to subspecialists for indicated cancer prevention care and procedures, access to evidence-based clinical decision support to optimize care for patients with these hereditary cancer syndromes does not exist. We posit that using primary care clinical encounters to promote appropriate subspecialist referral and testing of these high-risk patients will improve quality of care and clinical outcomes for patients with these hereditary cancer syndromes. To achieve this goal, we expand an effective patient-centered primary care clinical decision support (PC-CDS) system to guide evidence-based care of these high-risk patients, and assess intervention impact on up-to-date cancer prevention care, shared decision making, and patient self-efficacy in managing hereditary cancer risks. The web-based nature of the proposed PC-CDS system, its prior success in improving primary care for a wide range of other chronic conditions, and its high use rates in primary care settings suggest that this approach to care improvement may be an effective strategy to increase appropriate referrals and evidence-based preventive care of adults with these hereditary cancer syndromes. To assess intervention impact on care of adults with specific pathogenic or likely pathogenic gene variants related to HBOC or LS, we randomly assign 30 primary care clinics with an estimated 2488 study-eligible patients with laboratory or electronic health record (EHR)-documented HBOC or LS to usual care (N=15 clinics) or to the PC-CDS intervention (N=15 clinics) and assess intervention impact on (i) up to date evidence-based cancer prevention care, (ii) patient and clinician assessments of shared decision making related to cancer prevention care, and (iii) patient self-efficacy in managing their hereditary cancer risks. The project delivers a scalable and adaptive web-based CDS system that informs patients with specific genetic variants and their PCCs of evolving standards of care, facilitates timely access to a...