Association of immune and proliferation gene signatures and stromal tumor-infiltrating lymphocytes with clinical outcomes in patients with stage I triple-negative breast cancer.
Abstract
Background
One-third of patients with triple-negative breast cancer (TNBC) are diagnosed with stage I tumors. Biomarkers to stratify prognosis in this setting remain a major unmet need.
Methods
Tissue samples and clinicopathologic data were retrieved from consecutive patients with stage I TNBC (defined as ER <10% and HER2-negative) who underwent upfront breast surgery and received standard of care adjuvant systemic therapy at Dana-Farber/Brigham Cancer Center between 2016 and 2021. The TNBC-DX assay (Core Immune Gene [CIG] signature, proliferation signature) was applied to tumor tissue, and stromal tumor-infiltrating lymphocytes (sTILs) were centrally reviewed. Both biomarkers were tested for association with clinical outcomes using the Kaplan-Meier method.
Results
A total of 253 patients with stage I TNBC were included. Most tumors were ductal (88.9%) and high-grade (73.1%); 65.2% of patients received adjuvant chemotherapy. With 18 recurrence events observed, the 3-year recurrence-free survival (RFS) in the overall cohort was 95.0% (95% confidence interval [CI]: 92.1% - 98.1%) and the 3-year overall survival was 97.9% (95% CI: 95.9% - 100.0%). No significant differences in RFS were observed by TNBC-DX (n = 117 patients) or sTILs (n = 123 patients) category. However, a 3-year RFS of 100% (95% CI: 100% - 100%) was observed among the 29 patients with the highest CIG score quartile. A favorable prognosis was also observed in patients with high sTILs (>20%), who experienced a 3-year RFS of 97.0% (95% CI: 90% - 100%). Conversely, a high TNBC-DX proliferation score was numerically associated with poor outcomes, with a 3-year RFS of 83% (95% CI: 68% - 100%).
Conclusions
In this retrospective study, immune and proliferative features showed opposing prognostic trends in stage I TNBC. Their integration may improve risk stratification and warrants further investigation.