Fred Hutchinson Breast Cancer Clinical Validation Center

ABSTRACT There remain clear clinical and public health needs to improve the early detection of breast cancer. While mammography is an effective tool, there are issues with respect to optimizing its use and performance, and despite widespread screening breast cancer remains the 2nd most common cause of cancer related death among U.S. women. Through the current EDRN Clinical Validation Center (CVC) led by Dr. Li we have validated 15 candidate biomarkers through a series of Phase 2 and Phase 3 validation studies that involved successive series of three independent sets of preclinical samples. Outside of EDRN funding, Dr. Partridge has led the development of novel strategies to improve breast cancer detection based on quantitative markers derived from screening MRIs in high-risk women and application of artificial intelligence (AI) approaches in collaboration with Microsoft. Our overarching goal is to conduct Phase 2 and 3 validation studies of blood- based biomarkers and imaging strategies that will be integrated and jointly assessed in a Phase 4 validation study. Supporting this goal we propose the following 4 projects: Project 1: Phase 3 validation of early detection biomarkers for ER+ breast cancer; Project 2: Phase 2 and 3 validation of protein biomarkers for the early detection of breast cancer discovered using a mass spectrometry-based platform; Project 3: Phase 3 validation of quantitative markers and AI algorithms applied to MRI screening exams for the early detection of breast cancer in women at high risk; and Project 4: Phase 4 validation of blood-based biomarkers and imaging algorithms for the early detection of breast cancer. Additionally, we will provide biospecimens and expertise to support high quality PRoBE compliant EDRN discovery and validation studies across several cancer types. With the combined expertise of our multidisciplinary team of investigators and our engagement with key commercial partners, this CVC will both lead well-justified, rigorously designed validation studies and provide abundant resources to EDRN. Given the strength of our biomarker candidates, the sets of biospecimens that will be used, the study designs employed, and the clearly delineated clinical applications proposed, we anticipate that this work will yield near-term clinical impact.