title: Recent advances in systemic therapy: Advances in systemic therapy for HER2-positive metastatic breast cancer.
abstract: Human epidermal growth factor receptor (HER)2 over-expression is associated with a shortened disease-free interval and poor survival. Although the addition of trastuzumab to chemotherapy in the first-line setting has improved response rates, progression-free survival, and overall survival, response rates declined when trastuzumab was used beyond the first-line setting because of multiple mechanisms of resistance. Studies have demonstrated the clinical utility of continuing trastuzumab beyond progression, and further trials to explore this concept are ongoing. New tyrosine kinase inhibitors, monoclonal antibodies, PTEN (phosphatase and tensin homolog) pathway regulators, HER2 antibody-drug conjugates, and inhibitors of heat shock protein-90 are being evaluated to determine whether they may have a role to play in treating trastuzumab-resistant metastatic breast cancer.
authors: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Holcombe Boulevard, Houston, TX 77030, USA. pmorrow@mdanderson.org
authors: Phuong Khanh H
authors: PK
authors: Morrow
authors: Francisco
authors: F
authors: Zambrana
authors: Francisco J
authors: FJ
authors: Esteva
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics / Q000556:secondary*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics; D018450:Disease Progression; D016503:Drug Delivery Systems / Q000639:trends; D019008:Drug Resistance, Neoplasm; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D055264:Mucin-4 / Q000502:physiology; D009363:Neoplasm Proteins / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000502:physiology; D051059:PTEN Phosphohydrolase / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000737:chemistry / Q000502:physiology; D016879:Salvage Therapy; D015398:Signal Transduction / Q000187:drug effects; D000068878:Trastuzumab; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D018796:Immunoconjugates; D007334:Insulin-Like Growth Factor I; D055264:Mucin-4; D009363:Neoplasm Proteins; D051059:PTEN Phosphohydrolase; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D042461:Vascular Endothelial Growth Factor A; C524658:MUC4 protein, human; C467484:VEGFA protein, human; C508053:ERBB2 protein, human; C494929:PTEN protein, human