Abstract 1184: Association of immune microenvironment and race in the Carolina Breast Cancer Study

Abstract

Abstract Background: High levels of tumor infiltrating lymphocytes have been associated with favorable prognosis in triple negative and HER2-positive breast cancer (BC), especially in tumors with high mutation burden. Recently, our group showed that TP53 functional defects are strongly associated with black race in the Carolina Breast Cancer Study (CBCS). However, the immune microenvironment has been inconsistently associated with racial disparities in BC. Methods: To characterize immune phenotypes in BC, we curated a 50-gene NanoString immune panel and validated the gene set using RNA sequencing data from The Cancer Genome Atlas (TCGA). We applied the NanoString panel in the CBCS and estimated associations with immune infiltrates, BC intrinsic subtype, proliferation scores, p53 mutation signature and race using relative frequency differences (RFDs) as the measure of association. Results: Our 50-gene immune panel produced sample groupings in TCGA similar to that observed with the deconvolution algorithm, CIBERSORT. In CBCS (n=1208), we identified three immune groups primarily defined by features related to either adaptive immunity, innate immunity, or a quiet immune environment. Confirming that our expression-based groups reflect the tumor immune microenvironment, these immune groups correlated with histological evidence of immune cells from H&E slides in both TCGA and CBCS. The adaptive-enriched group was strongly associated with young age (≤50 years), high tumor grade, higher proliferation scores and the basal-like intrinsic subtype. TP53 mutant-like status was strongly associated with the adaptive-enriched immune group (RFD: 25.3%, p<0.0001), adjusting for age, race, and stage. Conversely, tumors in the innate and immune-quiet groups were primarily luminal (67.7%) and TP53 WT-like (60.2%). Black race was associated with the adaptive-enriched immune phenotype, even after adjusting for age and tumor stage (RFD: 7.6%, p=0.031). Conclusions: Our immune panel defines groups of BCs according to type of immune infiltration. Consistent with previous literature, we show that adaptive immunity is associated with aggressive breast tumors in CBCS. In addition, our data suggest an immunomodulatory effect of TP53 functional status–a variable we have previously associated with race in the CBCS. We provide evidence for a role of the immune microenvironment in racial disparities of BC. Further characterization of individual immune cell populations by race could reveal potential targets for BC intervention strategies that improve survivorship disparities. Citation Format: Alina M. Hamilton, Linnea T. Olsson, Benjamin C. Calhoun, Katherine A. Hoadley, Melissa A. Troester. Association of immune microenvironment and race in the Carolina Breast Cancer Study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1184.