Because preclinical and clinical evidence indicate that immune checkpoint blockade (ICB) may synergize with RT to promote systemic tumor regression, we explored the safety and efficacy of RT and concurrent tremelimumab-mediated cytotoxic T-lymphocyte associated protein 4 (CTLA-4) ICB with tremelimumab ± HER2-directed therapy with trastuzumab for BCBM. The gene discussed is CTLA4; the disease is neoplasm.