Project Summary/Abstract Breast cancer is the most common cancer and second leading cause of cancer mortality for women overall. Black women experience 40% higher breast cancer mortality rates than White women despite similar incidence rates. More than half of this racial disparity is attributable to triple negative breast cancer (TNBC), an aggressive subtype of invasive breast cancer that is twice as prevalent among Black vs. White women. TNBC is also more common among young women, often presenting before screening mammography is first recommended There is therefore a critical need to identify young women at risk for TNBC for earlier referral to screening and other prevention interventions. Several TNBC risk factors have been identified (e.g., limited breastfeeding, obesity, alcohol use), which are more prevalent in Black relative to White women and help to explain racial disparities in TNBC incidence. However, prior attempts to develop risk prediction models based on these risk factors have not succeeded. Thus, novel approaches for the identification of young women at risk for TNBC are necessary to close racial disparities in breast cancer mortality. Promising new evidence suggests that epigenetic biomarkers can overcome the limitations of traditional risk factor approaches and be used to personalize breast cancer prevention. Epigenetic-mediated changes in inflammatory processes as a result exposure to TNBC risk factors may contribute to TNBC pathogenesis. The identification of an epigenetic-based susceptibility/risk biomarker could be utilized in primary care settings to inform the recommendation to initiate screening mammography earlier and target modifiable risk factors among women at elevated risk for TNBC. To capitalize on this opportunity, the overall objective of this proposal is to develop the infrastructure to conduct this type of biomedical research in Delaware, an IDeA state that leads the US in both TNBC and alcohol-attributable breast cancer. We aim to develop a new prospective cohort to conduct comprehensive assessments of exposures for established and emerging TNBC risk factors in tandem with epigenetic immune patterns from a representative sample of breast cancer patients. We hypothesize that the cumulative exposure to reproductive, metabolic, alcohol, and environmental risk factors induces a distinct epigenetic immune signature. The long-term impact of this research includes reducing the burden of breast cancer for all women and closing racial disparities in breast cancer mortality.