The Role of Immunotherapy and Radiation Therapy in the Treatment of Breast Cancer

Breast cancer is the most commonly diagnosed non-cutaneous cancer and is the leading cause of cancer mortality in females worldwide. Breast cancer incidence has been increasing over the last few decades; simultaneously, novel therapeutic agents including immunotherapies and targeted therapies have become more prominent in use. Radiation therapy continues to serve as a cornerstone to breast cancer treatment in both early-stage and locoregionally advanced disease. Given the improvement in systemic agents, there is increasing interest in investigating the potential synergistic effect of radiation therapy and immunotherapy. As new trials and studies emerge demonstrating the clinical benefits of immune checkpoint inhibitors (ICIs) in breast cancer, especially in PD-L1-positive triple-negative breast cancer (TNBC), it is crucial to investigate the safety and efficacy of combining immunotherapy with radiation treatment. This narrative review discusses the impact of radiation therapy on anti-tumor immunogenicity, and examines the role of immunotherapy and radiation therapy in early-stage, locally advanced, recurrent, and metastatic breast cancer. We conducted a targeted literature search between 2010 and 2024, and included phase II/III clinical trials, mechanistic studies, and ongoing trials that evaluated the combination of immunotherapy (IO) and radiation therapy (RT). We discuss ongoing clinical studies, side effects, and optimal timing of combined IO and RT to enhance therapeutic outcomes.