ctDNA, TILs, and genomic signatures guide therapy modulation in early-stage triple-negative breast cancer
The review examines emerging biomarkers for early-stage triple-negative breast cancer, where approximately 40% of patients fail to achieve pathological complete response following neoadjuvant chemoimmunotherapy. Investigators highlight tumor-infiltrating lymphocytes as the most validated prognostic marker despite scoring standardization needs, while post-treatment circulating tumor DNA detection strongly predicts relapse, though optimal sampling timing remains undefined. Genomic signatures such as TNBC-DX offer reproducible prognostic data by combining immune and proliferative gene expression, with emerging evidence supporting multibiomarker integration to personalize treatment escalation or de-escalation. For diagnostic laboratories, these findings underscore the growing clinical utility of combining histopathological, liquid biopsy, and transcriptomic assays to refine risk stratification and guide therapeutic decisions.
The original study
The next-generation biomarkers in early-stage triple negative breast cancer.
- Authors
- Falcone F, Pietroluongo E, De Placido P
- Journal
- Current opinion in oncology
- Type
- Journal Article
- PMID
- 42750412
Original abstract
PURPOSE OF REVIEW: Despite maximal neoadjuvant chemoimmunotherapy, nearly 40% of early-stage triple-negative breast cancer (TNBC) patients fail to achieve pathological complete response, underscoring an urgent need for biomarkers capable of guiding treatment modulation. This review summarizes recent advances in tumor-infiltrating lymphocytes (TILs), circulating tumor DNA (ctDNA), and genomic signatures, exploring their potential integration into clinical decision-making. RECENT FINDINGS: TILs remain the most validated, cost-effective prognostic biomarker, although standardized scoring is still needed to overcome interobserver variability. ctDNA has emerged as a dynamic, real-time prognostic tool, with postneoadjuvant detection strongly predicting relapse and worse outcomes. Nonetheless, optimal sampling timing remains undefined. Genomic signatures, particularly TNBC-DX, provide standardized, reproducible prognostic information by integrating immune and proliferative gene expression. Emerging data suggest that combining these biomarkers may offer a complementary and synergistic effect. SUMMARY: Multibiomarker integration, supported by prospective validation and automated models, represents a promising approach to personalize treatment algorithms in early-stage TNBC, balancing efficacy and toxicity while guiding escalation and de-escalation strategies.