Optimizing Radiotherapy to Boost Systemic Immune Responses in Breast Cancer: A Critical Review for Breast Radiation Oncologists.

: Immunotherapy using immune checkpoint blockade has revolutionized the treatment of many types of cancer. Radiation therapy (RT)--particularly when delivered at high doses using newer techniques - may be capable of generating systemic anti-tumor effects when combined with immunotherapy in breast cancer. These systemic effects might be due to the local immune-priming effects of RT resulting in the expansion and circulation of effector immune cells to distant sites. While this concept merits further exploration, several challenges need to be overcome. One is an understanding of how the heterogeneity of breast cancers may relate to tumor immunogenicity. Another concerns the need to develop knowledge and expertise in delivering, sequencing and timing of RT with immunotherapy. Clinical trials addressing these issues are underway. We here review and discuss the particular opportunities and issues regarding this topic, including the design of informative clinical and translational studies.