Immune Checkpoint Inhibitors in Breast Cancer: Mechanisms, Biomarkers, and Future Therapeutic Strategies

The landscape of breast cancer treatment has been fundamentally transformed by the emergence of immune checkpoint inhibitors (ICIs), representing a paradigm shift from traditional cytotoxic approaches to precision immunotherapy. This comprehensive review examines the current state and future directions of ICIs in breast cancer, with particular emphasis on triple-negative breast cancer (TNBC) where these therapies have shown the most promise. We explore the mechanistic foundations of checkpoint inhibition targeting CTLA-4, PD-1, and PD-L1 pathways, examine resistance mechanisms and predictive biomarkers, and discuss emerging targets including LAG-3, TIM-3, and TIGIT. The integration of ICIs with conventional therapies has yielded encouraging clinical outcomes, leading to the first FDA approvals for immunotherapy in breast cancer. However, significant challenges remain in identifying optimal patient populations, overcoming resistance mechanisms, and developing robust predictive biomarkers. This review synthesizes current evidence from recent clinical trials and provides insights into future therapeutic strategies that promise to enhance the efficacy of immune checkpoint blockade in breast cancer treatment.