P2-06-03: Differential Expression of Breast Cancer-Associated Genes between Stage- and Age-Matched Tumor Specimens from African- and Caucasian-American Women Diagnosed with Breast Cancer.

Abstract

Background: Recent studies suggest that the poorer outcome of breast cancer patients observed in African-American women (AAW) may, in part, result from underlying genetic factors. The purpose of this study was to investigate gene expression differences between Caucasian-American women (CAW) and AAW that may contribute to this poorer prognosis. Methods: The expression of genes involved in breast carcinoma prognosis, response to therapy, estrogen signaling, and tumor aggressiveness was assessed in age- and stage-matched CAW and AAW paraffin-embedded breast cancer specimens. The Wilcoxon-Mann-Whitney Test was used to identify genes with a significant difference in expression between CAW and AAW. To determine if the differentially expressed genes could segregate between the CAW and AAW, we performed semi-supervised principle component analysis (SSPCA). Results: Twenty genes were differentially expressed between AAW and CAW. SSPCA incorporating these 20 genes separated AAW and CAW into two distinct groups. AAW were significantly (p < 0.05) more likely to display aberrations in G1/S cell-cycle regulatory genes, decreased expression of cell-adhesion genes, and low to no expression of ESR1, PGR, ERBB2 and estrogen pathway targets. Conclusions: The gene expression differences identified between AAW and CAW may contribute to more aggressive disease, resistance to therapy, enhanced metastatic potential and poor clinical outcome. Impact: These findings support the hypothesis that breast cancer specimens collected from AAW display distinct genetic differences compared to similar tissues obtained from CAW. Additional population-based studies are necessary to determine if these genetic variations contribute to the highly aggressive and treatment-resistant breast cancer phenotype frequently observed in AAW. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-06-03.