Neoadjuvant therapy for stage II-III triple-negative breast cancer: Current evidence, clinical boundaries and...

Neoadjuvant therapy is the standard therapeutic entry point for the majority of stage II-III triple-negative breast cancer (TNBC) cases. However, a number of practical questions remain unresolved in daily care; specifically, it remains unclear how the balance between treatment intensification and toxicity can be maintained, how heterogeneous trial platforms should be interpreted and how biomarkers can be effectively applied without overextending their clinical role. The present review summarizes the currently available evidence on chemotherapy backbones, selective platinum intensification, perioperative immunotherapy, radiotherapy integration, response-adapted strategies, post-neoadjuvant treatment, circulating tumor (ct)DNA-based residual-risk assessment and emerging antibody-drug conjugates. Anthracycline-taxane chemotherapy remains the reference backbone for stage II-III TNBC, whereas platinum is widely regarded as the selective intensifier in chemotherapy-alone platforms. In addition, carboplatin forms part of the evidence-based backbone of a KEYNOTE-522-like chemoimmunotherapy regimen. Among the immunotherapy strategies available, pembrolizumab-based perioperative treatment has the most convincing evidence in terms of pathological complete response, event-free survival and overall survival. Various biomarkers, such as programmed death-ligand 1, stromal tumor-infiltrating lymphocytes, homologous recombination deficiency, residual cancer burden and ctDNA, can improve biological and prognostic resolution. However, to the best of our knowledge few have been validated as stand-alone treatment selectors. Therefore, future management protocols should remain evidence-based, response-aware and explicit regarding the boundary between established practice and investigational escalation.