Patient Sociodemographic Factors Impact the Breast Cancer Microenvironment

Hormone receptor positive (HR+) breast cancer is the most common breast cancer subtype globally and remains a leading cause of cancer-related death in women. Black women diagnosed HR+ breast cancer experience significantly worse outcomes than White women, a disparity that persists even after accounting for factors such as healthcare access and educational attainment. Understanding the biological mechanisms underlying these differences has been limited by the underrepresentation of Black patients in genomic datasets. To address this gap, we generated an HR+ breast cancer transcriptomic dataset enriched for Black patients while controlling for access to healthcare and education level. Tumors from Black women showed enrichment of tumor microenvironment-related signatures, including increased collagen deposition and prognostically unfavorable T-cell landscapes. Data from in vitro and in vivo experimental models showed that race-aligned collagen deposition patterns were driven, at least in part, by tumor cell-intrinsic signaling and promoted metastatic phenotypes associated with poorer outcomes. Further analysis of the patient transcriptomic dataset revealed that unfavorable T-cell signatures previously attributed to race or ancestry were more strongly associated with poverty burden. Across multiple independent datasets, STAT4 emerged as a potential master regulator of this poverty-associated immune phenotype. Collectively, these findings suggest that molecular features of breast tumors are shaped by both biological and structural factors linked to self-identified race and socioeconomic disadvantage. These results demonstrate that integrating social determinants of health with molecular analyses can reveal mechanisms contributing to cancer outcome disparities and provide a foundation for the development of more effective and equitable precision oncology approaches.