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Immunogenomic Diversity of Triple-Negative Breast Cancers in Obese and Non-obese Black and White Women

ABSTRACT: Racial disparities in incidence and outcomes of triple-negative breast cancer (TNBC) have been attributed to ancestry, socioeconomic factors and/or obesity. We studied 253 TNBCs from 128 Black and 125 White women. Arms were balanced for age, AJCC stage, histological grade and molecular subtypes, and differed significantly in BMI distribution, obesity, and Area Deprivation Index. We examined survival rates, whole-transcriptome RNASeq and genetic ancestry. In our sample, Black race or obesity were not intrinsically predictive of poor outcomes. TNBC molecular portraits varied with stage and biological aggressiveness, irrespective of race. We identified a novel group of TNBCs with a distinctive luminal-like and stem-cell-like transcriptional profile that were equally distributed among Blacks and Whites. Genetic ancestry was highly admixed. Immune deconvolution showed a higher abundance of several immune cell populations in tumors from Blacks, which may have precision therapeutic significance, warranting further investigation of potential drivers of tumor immunity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE268851 | GEO | 2025/09/18

REPOSITORIES: GEO

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Project description:Background: Differences in breast cancer outcomes according to race/ethnicity have been reported. Hispanic/Latino (H/L) populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. Some studies suggest that breast cancer-specific mortality is higher in U.S. Hispanic/Latinas compared to non-Hispanic Whites (NHW) even after adjustment for socioeconomic status and education. The molecular profile of breast cancer has been widely described in NHWs but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian H/L women was Luminal B as defined by surrogate St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women. Methods: We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups. Results: We found 5 genes potentially modulated by genetic ancestry: ERBB2 (Fold Change = 2.367, padj < 0.01), GRB7 (Fold Change = 2.327, padj < 0.01), GSDMB (Fold Change = 1.723, padj < 0.01, MIEN1 (Fold Change = 2.195, padj < 0.01 and ONECUT2 (Fold Change = 2.204, padj < 0.01). In the replication set we found a statistical significant association between European ancestry fraction and the expression levels of ERBB2 (p = 0.02, B = 2.49) and ONECUT2 (p = 0.04, B = -4.87). We also observed statistical significant associations for ERBB2 expression with Indigenous American ancestry (p < 0.001, B = 3.82). This association was not biased by the distribution of HER2+ tumors among the groups analyzed. Conclusions: Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value.

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Immunogenomic Diversity of Triple-Negative Breast Cancers in Obese and Non-obese Black and White Women

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