Abstract:

Breast cancer is the most prevalent malignancy among women worldwide. In recent years, immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic strategy across different molecular subtypes of breast cancer, demonstrating significant clinical potential. This review systematically summarized the progress and clinical applications of ICIs in hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-overexpressing (HER2-positive), and triple-negative breast cancer (TNBC). In HR-positive breast cancer, the KEYNOTE-756 and CheckMate 7FL trials demonstrated that ICIs combined with neoadjuvant chemotherapy significantly improved the pathological complete response (pCR) rate, with greater benefits observed in programmed cell death-ligand 1 (PD-L1)-positive patients. Furthermore, the PROMENADE study indicated that estrogen receptor (ER)-low HER2-negative breast cancer patients achieved a pCR rate closer to that of TNBC rather than HR-positive breast cancer following ICIs treatment. In metastatic HR-positive breast cancer, the SACI-IO and DOLAF studies suggested that ICIs combined with antibody-drug conjugates (ADC) or poly (ADP-ribose) polymerase (PARP) inhibitors may provide clinical benefits for specific subgroups of patients. For HER2-positive breast cancer, the Keyriched-1 and Neo-PATH studies revealed that ICIs combined with anti-HER2 therapy might improve pCR rates in HR-negative/HER2-positive patients. However, the Impassion-050 and KATE2 trials failed to demonstrate widespread clinical benefits of ICIs in HER2-positive breast cancer. In TNBC, long-term follow-up data from the KEYNOTE-522 study showed that ICIs combined with neoadjuvant chemotherapy not only improved pCR rates but also conferred long-term survival benefits. Additionally, the Impassion-130, KEYNOTE-355, and TORCHLIGHT studies confirmed that ICIs combined with chemotherapy prolonged both progression-free survival (PFS) and overall survival (OS) in PD-L1-positive advanced TNBC patients. Meanwhile, treatment strategies combining ICIs with anti-angiogenic therapy, PARP inhibitors and ADCs have demonstrated promising efficacy in TNBC (SPARK and BEGONIA trial). Currently, ICIs combined with chemotherapy remains the primary treatment approach, while combination strategies involving ICIs with anti-HER2 therapy, endocrine therapy, ADCs, and anti-angiogenic therapy are actively being explored. However, challenges remain, including complex resistance mechanisms, heterogeneous treatment responses, and the management of immune-related adverse events. Future research should focus on refining patient stratification strategies and developing more precise combination therapies to improve long-term survival outcomes for breast cancer patients.

Key words: Breast cancer, Immune checkpoint inhibitor, PD-L1, Precision therapy