Breast Cancer Immunotherapy: A Team Science Approach.

Abstract

Immunotherapy has reshaped the treatment landscape of several malignancies, including breast cancer. While historically considered less immunogenic, breast cancer-particularly the triple-negative subtype (TNBC)-has demonstrated responsiveness to immune checkpoint inhibitors (ICIs). TNBC is characterized by higher tumor mutational burden, elevated PD-L1 expression, and increased tumor-infiltrating lymphocytes, making it a leading focus of immunotherapy development. In metastatic TNBC with PD-L1 expression, trials such as KEYNOTE-355 have shown improvements in progression-free and overall survival with the addition of the ICI, pembrolizumab to chemotherapy, leading to regulatory approval. In early-stage TNBC, KEYNOTE-522 established a neoadjuvant chemotherapy plus ICI as the standard of care for stage II and III tumors. This was based on improved pathologic complete response and event-free survival in this pivotal clinical trial regardless of PD-L1 expression. ICIs in other subtypes, such as HER2-positive and hormone receptor-positive/HER2-negative disease, remain under active investigation. Ongoing studies are also exploring novel strategies including dual immune checkpoint blockade, cellular therapies (e.g., CAR-T, TILs), cancer vaccines, and rational combinations with targeted agents and antibody-drug conjugates (ADCs). Biomarkers such as PD-L1, tumor mutational burden, immune gene signatures, and the gut microbiome are being evaluated to refine patient selection and predict response. Additionally, effective management of immune-related toxicities is critical, particularly in curative-intent settings. As the role of immunotherapy expands, a multidisciplinary, biomarker-driven approach will be essential to optimize outcomes and broaden its applicability across breast cancer subtypes.