Tailoring Escalation Adjuvant Therapy for Early-Stage Triple-Negative Breast Cancer in the CBCSG010 Clinical Trial Biomarker Analysis.

Background: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. The CBCSG010 trial is a prospective and multicenter phase III clinical trial confirming that adding adjuvant capecitabine significantly improved the 5-year disease-free survival (DFS) rate in patients with TNBC by 5.9%. In this study, we attempted to identify the specific population that benefited from adjuvant therapy.

Methods: In this retrospective exploratory analysis, we performed RNA sequencing of tumor tissues from patients with TNBC in the CBCSG010 clinical trial. A single-sample gene set enrichment analysis algorithm and survival analysis were performed to characterize the intrinsic molecular features of the TNBC microenvironment and assess the associations between immune-related gene expression levels or immune cell counts with capecitabine treatment efficacy. Additionally, we performed immunohistochemical staining of 2 markers, PD-L1 and CD8, and hematoxylin-eosin staining of stromal tumor-infiltrating lymphocytes (sTILs) on formalin-fixed, paraffin-embedded specimens to validate findings from bioinformatics analyses.

Results: We found that patients with TNBC with high immune-infiltration treated with capecitabine were more likely to have a better prognosis. We used a cutoff of ≥25 combined positive score (CPS) of PD-L1, ≥10% positive sTILs, and ≥10% positive cells of CD8 to define the "immune-hot" patients. Among immune-hot patients, Kaplan-Meier curves showed that 5-year DFS rates were 96.9% and 79.4% in the capecitabine and control groups, respectively (hazard ratio, 0.13; 95% CI, 0.03-0.52; P=.049 in favor of capecitabine). In the capecitabine group, the 5-year DFS rate was higher for immune-hot patients than for immune-cold patients (96.9% vs 76.4%; hazard ratio, 0.11; 95% CI, 0.04-0.29; P=.028).

Conclusions: Our study suggested that immune-hot patients with TNBC are more likely to benefit from adjuvant capecitabine, and that combining immunotherapy with chemotherapy may be expected to be more effective in immune-hot patients.