Molecular Mechanisms and Therapeutic Strategies for Immune Checkpoint Inhibitors in Breast Cancer: From Pathogenesis to Precision Medicine.

The advent of immunotherapy, and particularly the development of immune checkpoint inhibitors (ICIs), has revolutionized the landscape of breast cancer treatment, especially for triple-negative breast cancer. However, some patients still do not benefit from immunotherapy. Breast cancer is inherently an immunotherapy "cold" tumor, which results in suboptimal clinical outcomes when ICIs are used as monotherapy. Identifying additional immunotherapeutic targets and drugs, along with developing novel strategies for combination therapy, is crucial for addressing the challenges posed by immunotherapy resistance and tumor immune escape driven by multiple mechanisms. For instance, the combination of the programmed cell death protein 1 inhibitor, pembrolizumab, with chemotherapy has demonstrated remarkable clinical efficacy and is now the preferred first-line treatment for neoadjuvant, adjuvant, and metastatic breast cancer. This review discusses recently developed ICIs and focuses on strategies combining ICIs with chemotherapy, targeted therapy, nanotherapy, and other approaches in breast cancer. This review aims to summarize recent advances in immune checkpoint inhibitor-based combination strategies in breast cancer and to provide insights into improving therapeutic efficacy, overcoming treatment resistance, and ultimately enhancing patient outcomes.