Abstract 6121: Racial differences in the intratumoral immune cell infiltrate in luminal breast cancer

Abstract Background: Black women have a higher rate of breast cancer mortality compared with their non-Hispanic White (NHW) counterparts, with an 80% higher likelihood of breast cancer death from axillary node-negative, ER-positive (a. k. a. luminal) tumors (Hoskins et al, JAMA Oncol 2021). Black women are 30% more likely to have ER-positive tumors with a high-risk gene expression profile, indicating a role for tumor biology in this disparity (Hoskins et al, JAMA Oncol 2023). The underlying biological mechanisms responsible are unknown. The aim of this study was to investigate the immune cell infiltrate in ER-positive breast tumors as a potential driver of disproportionately aggressive luminal tumor biology among Black women. Methods: Gene expression data from ER-positive tumors diagnosed in women identified as Black or NHW in The Cancer Genome Atlas (TCGA) were deconvoluted with the CIBERSORT tool to estimate the relative intratumoral proportion of 22 immune cell types within each tumor. Differential analysis of imputed immune cell fractions comparing race was conducted with the Mann-Whitney test. P-values were adjusted for multiple comparisons with the false discovery rate (FDR) method. Linear regression of previously reported ancestry estimates for breast cancer patients in TCGA (Huo, et al, JAMA Oncol 2017) was used to test for association between African ancestry and proportion of regulatory T cells (Tregs) in tumors from Black women. Results: CIBERSORT analysis of tumors found a significantly increased proportion of Tregs in tumors from Black (n=86) than NHW (n=534) patients, with log2 fold-change= 0. 74 (FDR-corrected p-value= 0. 01). Plasma cells, T follicular helper cells and M0 macrophages were increased in tumors from Black women with uncorrected p-values 0. 05, but racial differences in these cell types were not significant after FDR correction (p 0. 1). Ancestry analysis among Black women indicated that African ancestry was not associated with the intratumoral proportion of Tregs (1 SD change in proportion African ancestry was associated with 0. 06 standard deviation increase in Tregs, p 0. 3). Confirmation of findings with a racially diverse breast tumor TMA from an independent cohort is ongoing and results will be presented. Conclusions: Increased pro-tumorigenic Treg infiltrate in ER-positive breast tumors from Black women may contribute to a disproportionately aggressive tumor phenotype and racial survival disparity. The findings could have therapeutic implications and suggest that immune checkpoint inhibitors may have increased activity against luminal breast cancer in Black patients. Although this study did not show a statistically significant effect for genetic admixture within African Americans, larger studies are needed to distinguish the contribution of ancestry vs. social context, environmental, and behavioral factors as the driver of this racial difference in tumor biology. Citation Format: Neha Hippalgaonkar, George Chlipala, Dezheng Huo, Garth Rauscher, Naiche Adler, Jan Kitajewski, Kent Hoskins. Racial differences in the intratumoral immune cell infiltrate in luminal breast cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 6121.