Project 1: Carolina Breast Cancer Study (CBCS): Linking Tumor Biology to Social - Abstract Black women suffer worse stage-specific mortality, in part due to higher relative frequency of late stage, ER-negative, high grade, and high genomic risk tumors (such as Basal-like and Luminal B tumors), but mortality differences are also persistent among those with ER+/HER2- disease. Early onset, severity, and poor survival in Black women’s breast cancer occurs in context of higher risk of multiple conditions, including obesity, cardiovascular disease, and most recently, deaths due to coronavirus. As such, breast cancer can be understood as part of a racialized syndemic, a convergence of multiple overlapping chronic and infectious disease epidemics related to structural racism in the United States. Measures of racial discrimination and racial animus are strong predictors of mortality but have rarely been linked to breast cancer outcomes specifically. Previous research has also linked ‘accelerated aging’, ‘premature age’ and ‘biological weathering’ to early onset of multiple diseases of aging in Black women, but not to breast cancer. Thus, ‘race’ is recognized as distinct from ancestry-related risk and should be understood in the social context of racism and must be linked to breast cancer outcomes in that context. Toward this goal, we seek to elucidate the specific, multi-level influence of racialized social determinants on tumor tissue and treatment patterns and resulting implications for breast cancer progression and recurrence. Using data from the diverse study population of Carolina Breast Cancer Study (50% black, 50% younger, 3000+ survivorship cohort), we have previously demonstrated important tumor biological variation by race. We have found that Black women have higher proliferation scores, higher risk of recurrence scores, more frequent p53 mutation status, and differential expression of DNA repair, stromal, and immune response signatures. We have also found that Black women have higher prevalence of treatment delay as well as different distributions of individual-level social and clinical factors such as quality of life, education, income, and comorbidities. More recently, we have observed racial differences in CBCS participant exposure to community-level factors (such as community advantage/disadvantage). Studying each of these domains individually is important, but joint analysis is needed to identify the most effective health equity interventions. Under a cells-to-society conceptual model of racialized breast cancer outcomes, we hypothesize that poor breast cancer outcomes arise due to aggregation of inequities across multiple levels (biological, individual, community, and structural). In context of race and racism, we propose to evaluate how inequities in individual (e.g., obesity, comorbidities) and community-level (disadvantage, advantage) exposures lead to biological (and especially immunologic and DNA repair) differences in tumors (Aim 1...