The Funding Mechanism of the Pilot Trial

Risk-stratified breast cancer screening strategies are a paradigm shift from the one-size-fits-all screening approach. Previous age-based screening strategies proved to be disadvantageous to specific high-risk populations, particularly BRCA1 and BRCA2 mutation carriers and individuals at high risk for aggressive interval breast cancers based on polygenic risk scores. This is an unmet clinical need as women at high risk of aggressive interval breast cancer would have a poorer long term outcome without intensive surveillance. Since joining the Women informed to screen based on measures of risk (Wisdom) Study (clinicaltrials.gov: NCT02620852) in 2020, the UChicago site has enrolled 1691 participants in Chicago. A growing number of studies have demonstrated the diagnostic equivalency of abbreviated MRI to the full MRI protocol. We launched the Chicago Alternative Prevention Study for BReast CAncer (CAPSBRACA; clinicaltrials.gov:NCT00989638) as a P20 Breast Cancer Disparities SPORE population science project to test the hypothesis that state-of-the-art genomic testing to identify women at increased risk, combined with state-of-the-art MRI techniques, could effectively detect and downstage aggressive interval breast cancers, and provide a personalized approach for management of high-risk women.  At our single Institution, 130 genomically defined higCSAYGINh-risk participants (mean age 42 SD+12) have been enrolled including 44 BRCA1, 42 BRCA2, 7 PALB2 and 25 with PRS >30%, suggesting common genetic variants can identify extremely high-risk women in practice. We have demonstrated the feasibility of our approach and the proposed study will test that it is clinically effective, adaptable, and can scale to optimize a comprehensive surveillance program for high-risk women at multiple clinical centers outside the University of Chicago. Our overall objective is to expand to additional imaging centers to broaden study sites and participants. The specific aims are to: 1) Implement biannual abbreviated MRI that includes ultrafast- DCE-MRI, with multicenter standardization; refine and expand our high-risk biannual abbreviated protocol to be fast, while both clinically accurate and generalizable across imaging facilities; 2) perform correlative science and quantitative analysis of MRI images and build an analysis package that can be disseminated to other centers; and 3) Develop and evaluate self-supervised deep learning (SSL) methods using UF DCE-MRI to enable fast and accurate computational biomarkers of breast cancer risk. CAPSBRACA translates innovative genomics and imaging research from the laboratory into meaningful clinical interventions and has the potential to address an unmet clinical need for early and accurate detection of aggressive young-onset breast cancers. It will impact the nearly 10,000 unscreened women in the US diagnosed each year with symptomatic breast cancer under 40 years of age, and the thousands of screened women at high risk of aggressive interval cancers.