Post-Chemotherapy Antibody-Based Continuation and Maintenance Strategies in HER2-Positive Metastatic Breast Cancer: A Translational Narrative Review

The treatment paradigm for HER2-positive metastatic breast cancer has evolved from continuous chemotherapy-based regimens to a model of finite chemotherapy induction followed by sustained antibody-driven disease control. The CLEOPATRA trial established dual HER2 blockade with trastuzumab and pertuzumab plus a taxane as the biological and clinical anchor of this approach, demonstrating that chemotherapy is administered for a defined induction period, after which antibody maintains disease suppression. An increasing body of clinical evidence indicates that antibody-based regimens can be combined with targeted agents, including CDK4/6 inhibitors or HER2 tyrosine kinase inhibitors, to achieve durable disease control without the need for continuous chemotherapy. In the PATINA trial, the addition of palbociclib to trastuzumab, pertuzumab, and endocrine therapy was associated with a clinically meaningful improvement in progression-free survival in hormone receptor-positive, HER2-positive metastatic breast cancer. At the same time, quality of life was maintained despite higher rates of hematologic toxicity. More recently, HER2-CLIMB-05 demonstrated that the addition of tucatinib to dual HER2 antibody therapy significantly prolonged progression-free survival, supporting a model of sustained, multi-agent HER2 pathway suppression. The monarcHER trial provided biological proof of concept that antibody plus CDK4/6 inhibition can achieve disease control without chemotherapy in hormone receptor-positive, HER2-positive disease. Collectively, these advances support a translational framework in which antibody therapy serves as a central component of treatment strategies, with targeted partners selected according to tumor biology and prior therapy. This review summarizes the biological basis, clinical evidence, and future perspectives of antibody-driven maintenance in HER2-positive metastatic breast cancer.