Introduction: This review provides an updated overview of the evolving pharmacologic landscape of human epidermal growth factor receptor 2 (HER2)-targeted therapies in breast cancer, highlighting key clinical trial data, recent indication expansions, resistance mechanisms, and emerging therapeutic agents in development.
Areas covered: This review draws on a comprehensive literature search of published studies and major oncology conference proceedings, focusing primarily on data from key phase III clinical trials of HER2-targeted therapies. Studies published within the past decade that have influenced current standards of care were prioritized.
Expert opinion: The treatment paradigm for HER2-expressing breast cancer is evolving rapidly. Trastuzumab deruxtecan has redefined management for both HER2-positive and the newly recognized HER2-low subgroups, while tucatinib offers a critical systemic option for central nervous system metastases. Optimal sequencing and resistance management remain critical challenges in this dynamic field. Nonetheless, HER2-targeted pharmacotherapy continues to advance rapidly, driven by innovative drug designs and strategic clinical developments.
Keywords: Breast cancer; HER2; antibody-drug conjugate; bispecific antibody; clinical trials; metastatic disease; pharmacotherapy; tyrosine kinase inhibitor.