ABSTRACT- Project 1 The incidence of triple-negative breast cancer (TNBC) in Louisiana is among the highest in the nation, particularly among African American (AA) women. AA women are also at high risk of obesity compared to European-American (EA). These apparently separate conditions may be linked by genetics, epigenetics and chronic inflammation. TNBC is a genetically heterogeneous group of diseases that includes multiple molecular subtypes based on transcript expression and somatic mutations. These subtypes respond differently to standard chemotherapy but are not yet routinely in clinical practice and it is unknown how well they apply to AA patients. Our preliminary data and the literature show that molecular signatures as well as inflammatory cells and T cells infiltrating TNBC may provide important prognostic information. As a part of this P20 Planning Grant project, we will explore the relationships between race, ancestry, tumor molecular portraits and immunological biomarkers in TNBC patients from Louisiana, as well as the possible role of obesity in modifying tumor immunity. Specifically, we wish to: 1) Retrospectively determine whether the molecular portraits of TNBC and/or the expression of immunological biomarkers differ between EA and AA patients, and whether obesity is associated with unfavorable immunological biomarkers irrespective of race and 2) Prospectively characterize and compare genomic and immunological portraits and response to neoadjuvant treatment of stage II/II TNBC tumors from EA versus AA patients, obese versus non- obese, and pre- versus post-treatment samples in cases that do not achieve pCR. These data will provide the basis for the development of novel clinically actionable biomarkers applicable to AA patients with TNBC and common comorbidities such as obesity. Additionally, this data can be used to inform decisions regarding prevention strategies, and to optimize treatment for underserved patients. As novel treatments such as immunotherapy become part of the therapeutic arsenal, our data will form the basis for hypothesis-driven studies of clinically informative biomarkers in our patient population.