Breast cancer immunogenicity as a spectrum: evolving concepts and therapeutic implications

Immunotherapy has revolutionized the therapeutic landscape for many cancers, but its application in solid tumors has lagged. There is now evidence that immunotherapy can improve outcomes in triple-negative breast cancer, but hormone receptor–positive (HR ⁺ ) breast cancer has traditionally been considered immunologically cold. However, emerging evidence challenges this binary paradigm, suggesting that a biologically relevant subset of HR ⁺ /human epidermal growth factor receptor 2–negative (HER2 ^– ) tumors exhibit meaningful immunogenic features and clinically relevant sensitivity to immune-based treatment. In this Review we summarize the current understanding of immunogenicity and clinical use of immune-based treatments across breast cancer subtypes. We argue for a broader view of a spectrum of breast cancer immunogenicity and highlight the importance of host factors, including parity and lactation history, in shaping antitumor immunity. Improved identification of immunologically active subsets and deeper mechanistic insight will be essential to expand the therapeutic benefit of immunotherapy to broader patient cohorts and to refine care of patients with breast cancer.