Abstract: The target therapeutic agents of HER-2 extracellular ligand-binding domain have become the core of breast cancer research.A small peptide molecule and an anti-HER2 extracellular domain monoclonal antibody conjugated with protein toxins, radioisotopes, and chemotherapeutic drugs (immunoconjugate) can improve efficacy and reduce systemic toxicity.Vaccines based on HER-2 extracellular region should protect patients from HER-2-overexpressing breast cancer growth.In this review, studies on targeted-block therapies of the HER-2 extracellular ligand-binding domain in breast cancer were discussed to provide references for clinical applications.