Impact of Allostatic Load and Neighborhood Contextual Factors on Breast Cancer in the Women's Health Initiative

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PROJECT SUMMARY/ABSTRACT Non-Hispanic Black (NHB) and Hispanic/Latinx women are disproportionately diagnosed with breast tumor exhibiting more aggressive phenotypes; and NHB women are dying from breast cancer at rates higher than every other racial/ethnic group in the United States (US). Due to structural racism (and its downstream effects), NHB and Hispanic/Latinx women experience more chronic stressors compared to non-Hispanic White (NHW) women. Emerging data, from our group and others, show that social and biologic factors contribute to the development of breast cancers with more aggressive tumor features that lead to the poorer outcomes. Evidence supports allostatic load – a measure of dysregulation across major physiologic systems including metabolic, cardiovascular, and immune/inflammatory systems – as a measure of cumulative physiologic stress and risk factor for adverse health outcomes. Data from a nationally representative sample of US women showed that allostatic load is inversely associated with socioeconomic status (SES) and positively associated with breast cancer among Black women, but not White women. No prior study has prospectively explored the impact of allostatic load and neighborhood contextual factors (simultaneously) on breast cancer in a large, diverse study sample. Here we propose to examine the impact of pre-diagnostic allostatic load score (ALS) and objectively measured neighborhood contextual factors on breast cancer incidence and phenotype in a large, nested case-control study of NHB, NHW, and Hispanic/Latinx participants in the Women’s Health Initiative (WHI). Our central hypothesis is that risk of breast cancer and aggressive tumors are attributable to the impact of higher ALS and socioeconomically deprived and racially segregated neighborhood context. Further, we hypothesize that allostatic load mediates the associations of neighborhood context with breast cancer, which differ by race/ethnicity. Leveraging WHI’s prospective design, rich epidemiologic and clinical data, and long-term follow-up, to test these hypotheses through the following aims: 1) Investigate associations of allostatic load with breast cancer risk and tumor phenotype; 2) Investigate associations of neighborhood contextual factors with breast cancer risk and tumor phenotype; and 3) Evaluate whether independent associations of allostatic load and neighborhood context with breast cancer differ by race/ethnicity. This study will have a high impact by yielding novel, prospective data on the impact of unfavorable neighborhood contextual factors and allostatic load (as an intermediate biological process/mechanism between neighborhood context and health) on breast cancer. Findings from this study will contribute new knowledge about the biological basis of long-term effects of structural racism and utility of ALS as a biomarker of cancer risk. These data are essential to developing evidence-based prevention strategies to improve cancer health equity.