Abstract GS3-07: Risk-based breast cancer screening is safe, preferred by women and identifies highest risk individuals: Results from WISDOM 1.0

Abstract Background: The goal of breast cancer (BC) screening is to reduce morbidity and mortality through the reduction of late-stage (Stage 2B or higher) cancers. Individual risk of BC varies substantially, and tailoring screening and prevention to individual risk could improve the focus on high risk women, reduce the burden of screening in low risk women and better allocate resources. Women Informed to Screen Depending On Measures of risk (WISDOM 1.0) Study was designed to test the non-inferiority of risk-based vs. annual screening for the primary outcome of Stage ≥2B BC, and to determine if risk-based screening is less morbid, preferred by women, and more conducive to prevention interventions. Methods: WISDOM 1.0, a randomized, preference sensitive pragmatic trial, compared the safety and morbidity of annual mammography versus risk-based screening, in which a woman’s BC risk is used to guide mammography initiation age, frequency, and the use of supplemental imaging and preventive interventions. Risk assessment included genetic testing (9 BC genes + polygenic risk scores (PRS)) and the Breast Cancer Surveillance Consortium (BCSC) v2 model, integrating breast density, to stratify women into four risk categories: highest (5-year risk >6%)/yearly mammography and MRI alternating every 6 months; elevated (top 2.5% of risk by age)/yearly mammography; average /biennial mammography; and lowest risk (no screening until 5-yr risk ≥1.3% or age 50). Risk-based participants had access to Breast Health Decisions, an educational tool to explain risk and options for risk reduction. Breast Health Specialists and genetic counselors provided consultations for women in the top 2.5% of risk by age or with pathogenic variants. Cancers, biopsies, chemoprevention, and imaging data were self-reported; 95% of all cancers were verified with medical records. Results: Over 7 years, 46,000 women enrolled, 61% chose to be randomized. Those who declined to randomize could elect to self-select their arm; 89% chose risk-based, regardless of age or geography. In the randomized cohort 77%, 6%, 4%, and 9% were White, African American, Asian, and Latina, respectively. There were 880 new BC diagnoses, of which 82 were Stage 2B or higher. Stage 2B cancer rate was non-inferior (p