Revisiting the standard of care for immune checkpoint inhibitors in early-stage triple-negative breast cancer: timing, duration, dose, combination, and patient selection

Triple-negative breast cancer (TNBC) is a highly immunogenic breast cancer subtype, rendering it particularly amenable to immunotherapy. Immune checkpoint inhibitors (ICIs), primarily targeting the PD-1/PD-L1 axis, have transformed the therapeutic landscape of early-stage TNBC, with KEYNOTE-522 trial establishing neoadjuvant pembrolizumab (continued as adjuvant) plus chemotherapy as the current standard of care. However, the substantial toxicity associated with the KEYNOTE-522 regimen, together with residual uncertainty regarding the relative contributions of neoadjuvant versus adjuvant pembrolizumab administration, underscores the need to optimize treatment intensity and refine ICI strategies. Herein, we provide an overview of immunotherapy and its clinical applications in TNBC. We integrate evidence from neoadjuvant and adjuvant ICI trials with mechanistic insights into the biologically optimal timing of immunotherapy. We further highlight emerging strategies aimed at optimizing the current standard-of-care regimen, with the potential to refine treatment timing, duration, dose, combination strategies, and patient selection for ICI therapy, thereby providing insights into future therapeutic approaches for early-stage TNBC.