Breast Cancer Program Project Summary / Abstract The mission of the Breast Cancer Program is to reduce morbidity and mortality from breast cancer through innovative basic and translational research and the conduct of impactful clinical trials. The Program’s members work collaboratively to advance knowledge across the continuum of breast cancer: from prevention, screening, and early diagnosis to treatment and survivorship. The goals are to increase cure rates and reduce morbidity among those who ultimately succumb to the disease and those who live with the late effects of therapy. The program has 117 members (73 primary and 44 secondary), representing all seven DF/HCC institutions and 16 academic departments. In 2019, peer-reviewed grant funding attributed to the Program was $8.1 million in direct costs from the NCI and $2.4 million from other sponsors. During the current funding period, primary Program members published 936 cancer-relevant papers. Of these, 28% were inter-institutional, 22% were intra-programmatic, and 42% were inter-programmatic collaborations between two or more DF/HCC members. To achieve the Program’s mission, our Specific Aims are to 1) Define and address the heterogeneity in triple-negative breast cancer; 2) Characterize the biology to improve outcomes from breast cancer metastases to the brain; 3) Improve the efficacy of immunotherapy for breast cancer; 4) Improve personalized local-regional therapy; and 5) Ensure that Program advances serve Massachusetts and the nation by addressing racial disparities and access to cancer care. These Aims align closely with the DF/HCC Strategic Plan and will be achieved through the established and invaluable CCSG infrastructure for collaborative transdisciplinary research, Shared Resources, and a unified clinical trials apparatus that accelerates translation of the Program’s laboratory discoveries to the clinic.