Intratumoral heterogeneity contributes to the chemotherapy prognosis of breast cancer.

Abstract

Previous studies have shown that intratumoral heterogeneity (ITH) is associated with poor clinical outcomes and is thought to be a mechanism of resistance to chemotherapy and radiotherapy. We aimed to determine how ITH affects the response to drug therapy in breast cancer (BC). We assessed ITH using mutated allele tumor heterogeneity (MATH) data from BC patients in the TCGA database. The study enrolled 515 patients with BC treated with chemotherapy from the TCGA database who had available data on survival, whole-exome sequencing, and genome-wide transcriptome sequencing. Additionally, 399 MSK-BRCA cohort patients were treated with chemotherapy. All statistical analyses were conducted using R. All comparisons were made using the two-sided Mann-Whitney test, Pearson's Chi-squared test, and the Kruskal-Wallis test. Statistical significance was defined as P values less than 0.05 (*P < 0.05). The survival package in R was used to conduct the analysis. Additional analysis was performed on 515 BC patients receiving adjuvant chemotherapy. MATH was associated with overall survival (OS) in multivariate analysis (hazard ratio (HR), 1.432; 95% confidence interval, 1.073-1.913; P = 0.015). Pathway enrichment and immune cell analysis revealed that the low MATH group had significantly higher infiltration of 24 different types of immune cells than the high MATH group. Individuals with low MATH scores had a longer OS than those with high MATH scores. Immune responses were significantly enhanced in breast cancer patients with low MATH scores.