Among patients with triple-negative breast cancer (TNBC), several studies have suggested that deregulated microRNA (miRNA) expression may be associated with a more aggressive phenotype. Although tumor molecular signatures may be race- and/or ethnicity-specific, there is limited information on the molecular profiles in women with TNBC of Hispanic and Latin American ancestry. We simultaneously profiled TNBC biopsies for the genome-wide copy number and miRNA global expression from 28 Latina women and identified a panel of 28 miRNAs associated with copy number alterations (CNAs). Four selected miRNAs (miR-141-3p, miR-150-5p, miR-182-5p, and miR-661) were validated in a subset of tumor and adjacent non-tumor tissue samples, with miR-182-5p being the most discriminatory among tissue groups (AUC value > 0.8). MiR-141-3p up-regulation was associated with increased cancer recurrence; miR-661 down-regulation with larger tumor size; and down-regulation of miR-150-5p with larger tumor size, high p53 expression, increased cancer recurrence, presence of distant metastasis, and deceased status. This study reinforces the importance of integration analysis of CNAs and miRNAs in TNBC, allowing for the identification of interactions among molecular mechanisms. Additionally, this study emphasizes the significance of considering the patients ancestral background when examining TNBC, as it can influence the relationship between intrinsic tumor molecular characteristics and clinical manifestations of the disease.

Androgen receptor (AR)-negative triple-negative breast cancer (TNBC), often termed quadruple-negative breast cancer (QNBC), disproportionately impacts women of African descent, leading to poorer overall survival (OS). MiRNAs regulate the expression of gene drivers involved in critical signaling pathways in TNBC, such as the AR gene, and their expression varies across races and breast cancer subtypes. This study investigates whether differentially expressed miRNAs influence AR transcription, potentially contributing to the observed disparities between African American (AA) and European American (EA) QNBC patients. Race-annotated TNBC samples (n = 129) were analyzed for AR expression status and revealed the prevalence of QNBC in AA patients compared to EA (76.6% vs. 57.7%) and a significant association of AR loss with poor survival among AAs. The Cancer Genome Atlas (TCGA) RNA-seq data showed that AAs with TNBC (n = 32) had lower AR mRNA levels than EAs (n = 67). Among TCGA patients in the AR-low group, AAs had significantly poorer OS than EAs. In our cohort, 46 miRNAs exhibited differential expression between AAs and EAs with QNBC. Ten of these miRNAs (miR-1185-5p, miR-1305, miR-3161, miR-3690, miR-494-3p, miR-509-3-5p, miR-619-3p, miR-628-3p, miR-873-5p, and miR-877-5p) were predicted to target the AR gene/signaling. The loss of AR expression is linked to poorer prognoses in AA women. The understanding of the specific miRNAs involved and their regulatory mechanisms on AR expression could provide valuable insights into why AA women are more prone to QNBC.