Abstract
Objective: To determine the association between objective (geospatial) and subjective (perceived) measures of structural racism and aggressive breast cancer tumor biology, defined using validated social adversity-associated transcription factor (TF) activity. Background: Structural racism is associated with shorter breast cancer recurrence-free survival, independent of individual, tumor, and treatment characteristics, suggesting potential unaccounted biological mechanisms by which structural racism influences tumor biology. The field of social genomics offers a mechanistic approach to study the influence of social adversity on tumor biology through validated TFs of social adversity. Methods: We quantified TF-binding motif prevalence within promoters of differentially expressed genes for 147 tissue samples prospectively collected on protocol. Covariate-adjusted multivariable regression analyzed objective measures of structural racism using the validated Index of Concentration at the Extremes and subjective measures of perceived discrimination using the Expanded Everyday Discrimination Survey with validated TFs of social adversity and aggressive biology—pro-inflammatory activity [nuclear factor-κB (NF-kB) and sympathetic nervous system (SNS) activity [cyclic 3′-5′ adenosine monophosphate response element-binding protein (CREB)], controlling for age, race/ethnicity, BMI, stage, grade, tumor type (TNBC, etc), and neoadjuvant therapy. Results: Increasing objective structural racism and perceived discrimination were associated with SNS activation (up-regulated CREB) and aggressive tumor biology (up-regulated NF-kB). Conclusions: To our knowledge, in the largest human social genomics structural racism study, objective measures of structural racism and subjective measures of perceived discrimination were significantly associated with TFs of aggressive biology and SNS activation, implicating SNS activation as one potential mechanism behind structural racism-associated survival disparities. We have previously shown that these TFs correlate with worse clinical outcomes such as shorter survival and higher Oncotype DX scores further reflective of aggressive tumor biology. These findings remain to be validated in a national cohort.
Citation Format: Neha Goel, Alexandra Hernandez, Susan Kesmodel, Michael Antoni, Steve Cole. Structural Racism and Aggressive Breast Cancer Biology [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-03-11.