Relationship between differences in RNA or protein expression and the effects of race/ethnicity on breast cancer outcomes.

Abstract

157Background: Race is associated with distinct outcomes for breast cancer patients. The purpose of this study was to evaluate whether there were differences in gene or protein expression patterns between breast cancers according to race/ethnicity and cancer subtype [(triple-negative (TN), estrogen receptor-positive/HER2-negative (HR+) and HER2-positive/with any ER status (HER2+)].Methods: Fine needle aspirates from primary breast cancers were obtained under a prospective tissue collection protocol. Transcriptional profiling was performed using Affymetrix HG-U133A platform in 376 patients and reverse phase protein array analysis (RPPA) was done for 177 distinct proteins in 255 patients from a separate cohort. Unsupervised clustering was conducted, as well as supervised comparison by race and tumor subtype. BRB-Array tools and Ingenuity Pathways software packages were used to analyze the data.Results: Median age was 50 years in both cohorts. In the RPPA cohort 54.5% of the tumors were HR+, 20.7% HER2+ and 24.71% TN. One hundred and forty-seven (57.6%), 47 (18.43%), 46 (18.1%) of the patients were white, Hispanic, and black, respectively. Unsupervised hierarchal clustering of the protein expression data showed no distinct clusters by race (permutation p values were 0.492, 0.489 and 0.494 for the HR+, HER2+ and TN tumors respectively). In the gene expression cohort, 54.2% of the tumors were HR+, 16.5% HER2+ and 29.3% TN. Two hundred and sixteen (57.5%), 111 (29.52%), and 32 (8.52%) patients were white, Hispanic and black, respectively. No probe set with an FDR < 0.05 showed any association with race by breast cancer subtype; similar results were obtained using pathway and gene set enrichment analysis methods.Conclusions: These results indicate that there are no large scale gene and protein expression differences between breast cancers of different races. The study size is too small to confidently exclude small scale expression differences in a limited number of proteins or RNAs. This analysis also did not examine the potential differential distribution of DNA nucleic acid polymorphisms, somatic mutations, gene rearrangements or copy number aberrations by race-ethnicity.