Advances in Immunotherapy for HER2 Low-Expressing Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is highly malignant with poor prognosis, and immune checkpoint inhibitors (ICIs) provide only limited survival benefits. A key emerging subtype is HER2 low-expressing TNBC, where HER2 expression influences immune microenvironment, clinical behavior, and therapeutic response. Antibody-drug conjugates (ADCs), particularly trastuzumab deruxtecan (T-DXd), have markedly improved survival and also exert antitumor effects through immune activation. Preclinical data suggest synergy when T-DXd is combined with ICIs. However, HER2-low TNBC often has an immune-suppressive microenvironment, underscoring the need for additional strategies. Tumor vaccines and genomics-driven targeted drugs, such as trastuzumab-α-amanitin conjugates, hold promise in reactivating antitumor immunity. This review summarizes current progress in immunotherapy for HER2 low-expressing TNBC, with emphasis on ADCs, combination regimens, and emerging precision strategies, aiming to inform future research and clinical application.