The Evolving Landscape of Immunotherapy in Triple-negative Breast Cancer: Mechanisms, Biomarkers, and Future Horizons

Triple-negative breast carcinoma (TNBC) is an aggressive malignancy with a historical paucity of targeted therapies, but recent years have seen a therapeutic revolution. Its distinct immunogenic profile, with an elevated tumor mutational burden and dense lymphocytic infiltration, makes it a prime candidate for immuno-oncology. This review synthesizes impactful research from 20232025 that defines the contemporary treatment paradigm. The author provides a comprehensive evaluation of the pivotal results that establish the significance of immunological checkpoint inhibitors (ICIs) in both curative and palliative contexts, most notably, the establishment of a significant overall survival improvement with the perioperative administration of pembrolizumab in the initial stages TNBC, a finding validated by the KEYNOTE-522 trial. Additionally, the author examines the transformative effect of antibody-drug conjugates (ADCs) directed against Trophoblast cell-surface antigen 2 (TROP2). Specifically, agents like sacituzumab govitecan are now established as a new therapeutic standard in the metastatic context. The necessity for strong biomarkers for prediction beyond the therapeutic target of checkpoint blockade, programmed death-ligand 1 (PD-L1) is examined, emphasizing the potential of lymphocytes that infiltrate tumors (TILs) and the transition towards dynamic, integrated multi-omic methodologies. Finally, the author explores the next frontier of innovation to overcome resistance, including rational combination strategies, "armored" CAR-T cell therapies, and personalized neoantigen vaccines. This review underscores the clear shift towards more complex, personalized, and potentially curative immunotherapy strategies for TNBC.