Differences in the immune microenvironment and genomic characteristics of TNBC in African American women compared to other races.

Abstract

e13028 Background: African American (AA) women are more likely to be diagnosed with triple negative breast cancer (TNBC) compared to other races and have lower pathologic complete response rate to neoadjuvant therapy. Our goal was to assess differences in the immune microenvironment and genomic characteristics of TNBC by race using the TCGA data set. Methods: We compared the expression levels of 13 previously reported immune metagenes (CTL, Mphages, MHC1, Tregs, IF1, NK, STAT1, MHC2, Giam, Tfh, Tinh, Tstim, LCK), histologic tumor infiltrating lymphocyte (TIL) count and overall mutational load, neoantigen load, clonal heterogeneity assessed using the MATH score, amplification and deletion loads of between AA (n = 58) and non-AA TNBC (n = 114). Data was downloaded from the TCGA website, immune metagene expression and MATH scores were calculated as previously reported. Distributions between cohorts were compared using the Mann-Whitney U-test. Results: Among the immune metagenes only the cytotoxic T cell (CTL) metagene showed lower expression in AA patients (3.64 versus 4.08, unadjusted p = 0.046). TIL count was available in 51 of 58 AA and 91 of 114 of non-AA cases, and no significant difference was observed between the racial groups (p = 0.55). We also did not observe statistically significant differences in the mutational load (p = 0.36), neoantigen load (p = 0.38), clonal heterogeneity represented by the MATH score (p = 0.54), and amplification and deletion loads (p = 0.23 and 0.83 respectively) between the two TNBC race groups. We also assess the expression distribution of the immune signatures in an independent Affymetrix gene expression dataset including 40 AA and 323 non-AA patients with TNBC. Similar to the TCGA, there were no significant race differences in the immune signatures, including in the CTL metagene. Conclusions: These results suggest that the differences in prevalence and treatment response seen between TNBC in AA and non-AA patients are unlikely to be due to differences in the immune microenvironment and the genomic landscape of TNBC. However, more subtle comparison in the immune biology of these cancers can only be studies with more focused methods.