Systemic molecular disparities in Black vs. White breast cancer survivors: Beyond socioeconomic determinants

Objective: Mortality from breast cancer (BC) is 27% higher among non-Hispanic Black (NHB) than among non-Hispanic White (NHW) women. The objective of this study is to investigate molecular mechanisms underlying the higher mortality rate in NHB BC survivors, independent of lifestyle and socioeconomic factors. Experiment: Buffy coats were collected from NHW and NHB BC survivors (n=12 each, 6 months - 3 years post-treatment) and from cancer-free participants (n=6 each). Principal Component Analysis (PCA) and Fisher's exact tests were performed on clinical variables. Gene expression was measured with the nCounter Immunology Panel (594 genes), Metabolic Pathways Panel (768 genes), and Qiagen RT² Profiler PCR Array Human DNA Repair Kit (84 genes). Differential expression analysis was performed for two comparisons: (A) Black vs. White BC survivors, and (B) Black vs. White non-cancer controls. A two-sample Student's t-test with multiple testing correction (Benjamini-Hochberg false discovery rate (FDR)) was performed with log 2 FC and filtered for significance (p < 0.05, FDR < 0.25, |fold change| > 2). An Ingenuity Pathway Analysis (IPA) was performed, and pathways with -log p value>=1.3 and Z-score >=2 or <=-2 were considered significant. Result: PCA of clinical factors (age, BMI, and treatments) and stage distribution (Fisher's exact test) showed similar profiles between NHB and NHW BC survivors, suggesting that molecular differences in downstream analyses are unlikely to be driven by clinical or lifestyle factors. Differential expression analysis suggested that only two genes were significantly different between non-cancer NHB and NHW controls, but 92 genes, including IL8 and POLB, were significantly altered between cancer survivors. These findings suggest that the differential expression patterns are driven by cancer survivorship rather than baseline racial differences. Ninety-two genes were then analyzed with IPA, and 17 pathways were deemed significant. The Th1 and TP53 expression and degradation pathways were more active. Abasic site repair pathways were found to be inhibited in NHB survivors, consistent with our previous report. Conclusion: Our pilot study showed that despite similar clinical profiles, NHB and NHW BC survivors exhibit distinct molecular signatures. In the future, we plan to validate these pathways and use public databases such as TCGA to evaluate how these genes affect cancer survival. Addressing these pathway differences may be key to achieving true equity in breast cancer survivorship.