Abstract
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.
Highlights
Triple-negative breast cancer (TNBC) accounts for 15–20% of breast cancers that lack estrogen receptor (ER) and progesterone receptor (PR) expression and human epidermal growth factor 2 (HER2) amplification (Perou et al, 2000; Harbeck and Gnant, 2017)
Considering the important role of tumor microenvironment (TME) in tumor progression, we investigated the prognostic significance of different TNBC microenvironment phenotypes taking advantage of the longterm survival data of the 100 patients from the PATTERN cohort
Considering the different features of genomic alteration of the microenvironment phenotypes in TNBC (Xiao et al, 2019), we further explored the association between the microenvironment phenotypes and the efficacy of adjuvant chemotherapy regimens
Summary
Triple-negative breast cancer (TNBC) accounts for 15–20% of breast cancers that lack estrogen receptor (ER) and progesterone receptor (PR) expression and human epidermal growth factor 2 (HER2) amplification (Perou et al, 2000; Harbeck and Gnant, 2017). Higher risk of relapse and metastasis and lack of therapeutic targets are major problems in TNBC treatment at present (Bianchini et al, 2016; Denkert et al, 2017). Compared with other subtypes of breast cancer, TNBC usually has higher immunogenicity (Lehmann et al, 2011; Burstein et al, 2015). Immune infiltration in the tumor microenvironment (TME) is associated with response to treatment and prognosis of TNBC (Loi et al, 2014; Denkert et al, 2018). 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 “immuneinflamed” cluster. The immune-inflamed cluster is considered as “hot tumor” while the other two are considered as “cold tumor”
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