Immunotherapies for Breast Cancer: From Checkpoint Inhibition to Emerging Cellular Therapies

Abstract

Breast cancer remains a leading cause of cancer-related morbidity and mortality worldwide, with therapeutic response being shaped by the unique biology of each breast cancer subtype. Immunotherapy has emerged as a transformative approach in selected disease subtypes, with the most successful results being found in relation to triple negative breast cancer (TNBC). Immune checkpoint inhibitors (ICIs) have transformed the management of many solid tumours. In breast cancer, they have demonstrated clinical benefit in TNBC when combined with chemotherapy, establishing a new standard of care in both early-stage and metastatic settings. However, the majority of breast cancers exhibit intrinsic or acquired resistance to checkpoint blockade, driven by low tumour immunogenicity and an immunosuppressive tumour microenvironment. Recent advances in cellular immunotherapy could represent the next frontier in the therapeutic landscape of breast cancer. Chimeric antigen receptor (CAR) T cell targeting antigens such as HER2, ROR1, MUC1, mesothelin, and B7-H3 are entering early-phase clinical evaluation with results eagerly awaited. Parallel approaches, including tumour-infiltrating lymphocyte (TIL) therapy, T cell receptor (TCR)-engineered T cells, and CAR-natural killer (CAR-NK) platforms, offer alternative mechanisms to overcome antigen presentation barriers and immune evasion. This review summarises current clinical evidence for immunotherapies in breast cancer, highlights emerging cellular strategies, and discusses key challenges including antigen specificity, off-tumour toxicity, and tumour microenvironment-mediated resistance. Future progress will likely depend on rational combination approaches and next-generation engineered immune cell platforms to achieve durable and personalised clinical benefit.