PROJECT SUMMARY/ABSTRACT: OVERALL Using the well-established framework of a very active and strong multidisciplinary Vanderbilt-Ingram Cancer Center (VICC) Breast Cancer Program that is robustly supported by the SPORE mechanism, we have made significant progress in our current project period. With supplemental funding, our overall goal remains the same: To conduct collaborative, multidisciplinary and mechanism-based translational research that will have the highest possible impact on women and men with or at risk for breast cancer. After planning and internal and external advisory board evaluation, we propose to continue our research on three translational projects, primarily targeting triple-negative breast cancer, with integrated guidance from patient advocates, to ensure that we are inclusive of the patient perspective in meeting our goals. The projects are as follows: Project 2 - Strategies to Improve Outcomes for TNBC Patients Integrating Subtype-specific Genomic and Immune-based Discoveries; Project 4 - Targeting Antigen Presentation to Improve Immunotherapy Responses in Breast Cancer; and Project 5 – Liquid Biopsies to Guide Therapies in Triple-Negative Breast Cancers. The projects require three highly integrated shared core resources: Administration and Engagement, Biostatistics and Bioinformatics, and Pathology and Tissue Informatics. The cores bring innovative technology, resources, and personnel with project-specific expertise to the overall VICC Breast SPORE Program and do not duplicate pre- existing shared resources available at VICC or Vanderbilt University Medical Center (VUMC). We have an expert multidisciplinary team that will accomplish the proposed aims and continue to have productive translational collaborations with other Breast Cancer Programs, SPOREs, and national and international groups.