Chronic Social Stressors and Biological Embodiment of Risk in Breast Cancer Mortality

Breast cancer mortality differs significantly by several demographic factors, including socio-economic status, access to care, geographic residence and race/ethnicity. Despite extensive investigation, the known causes to date do not adequately explain this mortality gap. Largely missing in the literature is a rigorous examination of how exposure to chronic societal stress (CSS) might impact adverse breast cancer outcomes. Multiple lines of evidence, when considered together, indicate that this exposure merits investigation. CSS (e.g., interpersonal conflict, limited residential resources, etc) is associated with a range of adverse health effects, and chronic psychosocial stress due to CSS can become embodied via hyperactivation of the hypothalamic pituitary adrenal (HPA) axis, leading to elevated markers of multisystem allostatic load. We hypothesize that exposure to CSS contributes to—and helps explain—excess breast cancer mortality in certain demographic groups, however, 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 cancers and a 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 participants representing various socio-economic, access and race/ethnic demographic groups, including from southern states with a history of CSS; moreover, they obtained extensive baseline epidemiologic and covariate data. We will newly assess measures of CSS exposure across multiple domains, multiple geographic levels (e.g., census tract, state level), and multiple time points across the lifecourse. Our study will provide the first thorough prospective evaluation of the distinct influence of CSS, above and beyond other population-level risk factors, on breast cancer outcomes in a large, broadly representative US cohort. By quantifying the distinct impact of CSS and exploring pathways that may mediate this association, our study will: i) illuminate specific social and biological drivers of breast cancer outcomes, ii) improve the poor accuracy of current breast cancer prognostic models across various demographic groups, and iii) inform primary prevention strategies to mitigate CSS exposure and reduce breast cancer mortality.