Systemic Racism and Biological Embodiment of Risk in Breast Cancer Mortality

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Black women experience much higher breast cancer mortality than any other race/ethnic group in the US. Despite extensive investigation, the known causes to date do not adequately explain this mortality gap. Largely missing in the disparities literature is a rigorous examination of systemic racism – i.e., how exposure to an overarching environment of systemic racism (SR) might impact breast cancer outcomes in Black women. Multiple lines of evidence, when considered together, indicate this exposure merits investigation. SR (e.g., perceived discrimination, residential segregation) is associated with a range of adverse health effects in Blacks, and chronic psychosocial stress due to SR can become embodied via hyperactivation of the hypothalamic pituitary adrenal (HPA) axis, leading to inflammatory, metabolic and epigenetic dysregulation. Thus, we hypothesize that exposure to SR leads to alterations in key biological pathways, which in turn contribute to excess breast cancer mortality in Black women. No empirical study has directly tested this hypothesis in a single cohort. To address this gap, we will generate a new prospective cohort with 2,498 incident breast cancer and 2,678 sub-cohort random sample from two parent cohorts -- the REasons for Geographic and Racial Differences in Stroke (REGARDS) and Southern Community Cohort Study (SCCS) cohorts. Both parent cohorts over sampled Blacks and include participants from southern states with a history of SR and obtained extensive baseline and biomarker data, enabling us to measure biomarkers of inflammation and metabolic dysregulation. We will newly assess measures of SR at the structural and interpersonal levels and characterize epigenome-wide DNA methylation profiles. Our study will conduct the first thorough prospective evaluation of the distinct influence of SR, above and beyond other racially pattered risk factors, on breast cancer disparities in a large, diverse cohort. By quantifying the distinct impact of SR on breast cancer mortality, and identifying pathways and biomarkers that mediate this association, our study will help improve the poor accuracy of breast cancer prognostic models in Black women, and inform primary prevention strategies focused on mitigating SR to reduce racial disparities in breast cancer mortality