title: Emerging approaches for treating HER2-positive metastatic breast cancer beyond trastuzumab.
abstract: Because metastatic breast cancer (MBC) is incurable in most cases, the goals of treatment are improvement in quality of life, management of symptoms, and prolonged survival. The human epidermal growth factor receptor 2 (HER2) is overexpressed in up to 30% of breast tumors, and before the development of HER-targeted therapy, HER2 positivity was predictive of poorer clinical outcomes. Trastuzumab and pertuzumab (anti-HER2 monoclonal antibodies), lapatinib (a small molecule inhibitor of HER2 and the epidermal growth factor receptor [EGFR]) are approved for treating HER2-positive MBC in the United States. Although trastuzumab plus chemotherapy is currently regarded as the first-line standard of care for HER2-positive MBC, it is not without shortcomings; these include its association with certain adverse events (e.g. cardiotoxic effect) and development of resistance. A number of investigational agents that target HER2 and other members of that receptor family are in clinical development for patients with HER2-positive MBC whose disease has progressed on trastuzumab. In addition, in an effort to overcome treatment resistance, clinical trials are evaluating combination therapy (investigational HER-targeted agents with trastuzumab or lapatinib). This review discusses recently completed and ongoing phase II and III clinical trials of investigational HER-targeted agents in the setting of trastuzumab-progressive, HER2-positive MBC.
authors.affiliation: Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Chicago, USA. Electronic address: w-gradishar@northwestern.edu.
authors.forename: W J
authors.initials: WJ
authors.lastname: Gradishar
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008453:Maytansine / Q000031:analogs & derivatives / Q000627:therapeutic use; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000068878:Trastuzumab
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077341:Lapatinib; D008453:Maytansine; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C485206:pertuzumab
keywords: HER inhibitors; HER2-positive; metastatic breast cancer; monoclonal antibodies; neoadjuvant therapy; trastuzumab