Abstract A082: Differential expression of transcriptomic pathways contributes to survival disparities between Black and White women with breast cancer

Abstract Background: Non-Hispanic Black (NHB) women have higher breast cancer-specific mortality than Non-Hispanic White (NHW) women, overall and in each BC subtype. We hypothesized that this disparity is partially mediated by differential expression of genes in immune pathways in breast tumors. Using transcriptomic profiling of breast tumors in a longitudinal cohort, we aimed to identify molecular markers with distinct expression and prognostic patterns in NHB and NHW women. Methods: We performed transcriptomic profiling with NanoString nCounter Breast Cancer 360 panel on treatment-naïve primary breast tumors from 1,377 women (215 NHB and 725 NHW) diagnosed in 2005-2015 with stage II-III breast cancer at Kaiser Permanente Northern California, with a median survival time of 10.2 years. To assess body composition at diagnosis, we segmented muscle and adipose tissue on staging CT scans. Multivariable-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HR) for breast cancer-specific mortality. Pathway activity was quantified using Z-score normalized Single Sample Gene Set Enrichment Analysis (ssGSEA). Mediation analysis was conducted to evaluate whether adiposity and comorbidity metrics mediate the observed differences in pathway expression. We used Fine-Gray models with pathway score-by-race interaction terms to identify pathways associated with differential breast cancer–specific mortality between racial groups. Results: Compared to NHW, NHB women had increased breast cancer-specific mortality in overall (HR 1.49, 95%CI 1.10-2.02) and within basal subtypes (HR 1.68, 95%CI 1.08-2.62). Across subtypes, NHB women had higher expression of Treg, inflammatory chemokines, and antigen presenting machinery, with lower expression of macrophage, mast cell, PD-1, hypoxia, and stroma pathways. Within subtypes, higher Treg and lower mast cell and hypoxia pathway expression was also observed in basal-like tumors. Visceral adipose tissue and Charlson comorbidity index score mediated racial differences in pathway expression. In NHB patients, several immune-related pathways (e.g., Treg, IFN-γ, PD-L1, PD-L2, TIS, TIGIT, IDO1, cytotoxicity) were associated with better prognosis, while B7-H3 expression was linked to worse prognosis. These associations were not observed in NHW patients. Conclusions: We observed racial differences in tumor transcriptomics, particularly in immune and microenvironment pathways. Some immune pathways also emerged as prognostic biomarkers in NHB patients. Our results highlight potential therapeutic pathways to reduce breast cancer survival disparities. Citation Format: Fangyuan Chen, Adrienne M. Parsons, Elizabeth A. Mittendorf, Wendy Y. Chen, Sandra S. McAllister, Erica T. Warner, Elizabeth C. Feliciano. Differential expression of transcriptomic pathways contributes to survival disparities between Black and White women with breast cancer [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A082.