The next-generation biomarkers in early-stage triple negative breast cancer

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.

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.

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.