The Role of Racial Disparities in Gene Expression Profiling for the Prediction of Therapeutic Response in Patients With Breast Cancer

Abstract

PURPOSE Genetic variations affecting gene expression play a crucial role in breast cancer chemotherapy response. This study investigates how gene expression profiles impact treatment outcomes and explores racial disparities in chemotherapy response among breast cancer patients. METHODS Utilizing data from The Cancer Genome Atlas (TCGA) via Cbioportal, gene expression profiles of 8,132 breast cancer patients from 23 studies were analysed. 2030 patients were categorized into 1,743 white and 287 black. Among them, 407 received cyclophosphamide, 291 received doxorubicin, and 215 received tamoxifen or combination therapy. Mutual exclusivity was assessed, and P-values were calculated using Fisher's exact test, assuming the null hypothesis that the frequency of alteration occurrence in a pair of genes is proportional to independent occurrences in each gene. The enrichment of genes between patients of European ancestry and African descent was analysed. Kaplan-Meier plots were generated, and P-values from the log-rank test were determined to assess survival differences. RESULTS Significant differences in gene expression profiles were observed between white and black/African American patients. Notably, the GCA (p < 0.001) gene, encoding a calcium-binding protein abundant in immune cells, showed complete alteration in less than 1% of white patients and was absent in black/African American patients. Commonly expressed genes with variations in both racial groups included TP53, PIK3CA, IGLV3-25, CSMD1, ERBB2, MYC, TTN, CDK12, and CASC8. Ethnicity influenced chemotherapy response, with patients of European ancestry exhibiting superior overall survival. Both racial groups showed heightened response to cyclophosphamide but reduced response to tamoxifen. CONCLUSION Patients of European ancestry had better survival rates compared to black or African American patients, possibly due to differences in gene expression profiles amongst other factors. However, the specific role of the GCA gene in breast cancer pathogenesis remains unclear. Understanding gene expression patterns, particularly in tumour-infiltrating lymphocytes, may shed light on immune responses in breast cancer. Racial disparities in gene expression profiles significantly impact chemotherapy response and patient outcomes, highlighting the need for further research into genetic determinants and immune responses to refine therapeutic interventions. This study highlights the importance of personalized treatment strategies informed by genetic and racial considerations in breast cancer management.