整合临床与多组学数据以刻画墨西哥湾沿岸乳腺癌的种族差异

Ethnic disparities in breast cancer (BC) incidence, subtype distribution, and outcomes remain a significant public health concern in the United States. African American women (AAW) are disproportionately affected by aggressive disease, particularly triple-negative BC (TNBC). Whether these disparities are mirrored in Gulf Coast populations and whether tumor-level molecular features contribute to them remains unclear. This study integrates clinical data with tumor multiomics profiling to characterize ethnic differences among women diagnosed with BC within the USA Health System. Clinical and demographic information from 1,229 women diagnosed with BC from 2016 to 2024 was reviewed; 1,059 women (447 AAW, 612 WAW) with complete datasets were included. Age at diagnosis and BC subtype distribution were compared between ethnic groups. Tumor samples from 20 women (13 TNBC, seven non-TNBC; both AAW and WAW represented) and three normal breast tissues were analyzed using the NanoString BC360 transcriptomic and MO protein panel. Multiomics analyses investigated differences in signaling pathways associated with ethnicity and subtype. AAW exhibited approximately twice the frequency of TNBC observed in WAW and were more often diagnosed before age 55. These patterns parallel national trends and highlight a significant local disparity in disease presentation. The nCounter multiomics assay revealed substantial differences in gene and protein expression profiles between breast cancers from AAW and WAW. At the transcriptomic level, CCNA1, PIK3CA, SOX2, DDX39A, BRCA2, TMPRSS4, and BMP6, among others, showed lower expression in AAW tumors than in WAW tumors.In contrast, CD24 and RAC3 showed higher expression in the former group than in the latter. At the protein level, cyclin A2 and the insulin receptor were underexpressed in AAW tumors. Insulin, Notch1, melanoma GP100, and cIAP2, among others, were overexpressed in AAW tumors compared to those from WAW women. These findings demonstrate that the ethnic disparities in breast cancer observed nationally are also present in the Gulf Coast region and are accompanied by distinct molecular signatures at both the transcriptomic and protein levels. The differential expression of key oncogenic, immune, metabolic, and signaling pathway markers between tumors from AAW and WAW suggests that biological factors may contribute to the more aggressive disease patterns seen in AAW. Further studies with larger cohorts are warranted to validate these results and to explore their implications for personalized risk stratification and targeted therapeutic strategies. This study was funded by a grant from the Breast Cancer Research Foundation of Alabama (BCRFA) to LPY.