Prognostic Effect of Microenvironment Phenotype in Triple-Negative Breast Cancer: Biomarker Analysis of a Prospective Trial

Background: The microenvironment of triple-negative breast cancer (TNBC) can be divided into three clusters based on bioinformatics-based immunogenomic analysis: the immune-desert cluster, the innate immune-inactivated cluster, and the immune-inflamed cluster. The immune-inflamed cluster is considered as hot tumor while the other two are considered as cold tumor. Methods: To investigate the prognostic effect of microenvironment phenotypes on TNBC, we compared relapse-free survival (RFS) of different phenotypes in 100 patients with RNA sequencing-based expression data from the PATTERN trial (NCT01216111, published in JAMA Oncol 2020), which indicated a superior efficacy of adjuvant paclitaxel-plus-carboplatin regimen compared to the regimen of cyclophosphamide/epirubicin/fluorouracil followed by docetaxel for TNBC. We also analyzed the efficacy of the two regimens for different immune phenotypes to explore potential treatment strategies. Results: No significant difference in RFS was observed between the hot tumor and the cold tumor (hazard ratio [HR] = 0.68, 95% confidence interval [CI] 0.28-1.66, P = 0.40). However, the hot tumor subtype was associated with significantly longer RFS in node-positive patients (HR = 0.27, 95%CI 0.07-0.97, P = 0.03). Consistently, a similar trend to improved RFS of the hot tumor phenotype was detected in patients with stage pT2-3 tumors (HR = 0.29, 95%CI 0.06-1.30, P = 0.08). Furthermore, no significant difference in RFS between the two treatment arms was observed in patients with hot tumor (HR = 0.39, 95% CI 0.08-2.01, P = 0.24) or cold tumor (HR = 1.05, 95% CI 0.39-2.82, P = 0.92). Conclusion: The microenvironment phenotype in TNBC might have prognostic significance to patients with a high risk of recurrence. The association of the microenvironment phenotypes with the efficacy of adjuvant chemotherapy for TNBC remains to be further studied.

Automated summary

The study found that in patients with triple-negative breast cancer, the immune-inflamed tumor subtype may be associated with longer RFS in node-positive patients and pT2-3 stage tumor patients. However, in terms of treatment efficacy, there was no significant difference in RFS between the two regimens for either hot or cold tumor phenotypes.