title: Current status of anti-human epidermal growth factor receptor 2 therapies: predicting and overcoming herceptin resistance.
abstract: Human epidermal growth factor receptor 2-overexpressing (HER2+) breast cancer occurs in 20% to 25% of cases and is associated with poor prognosis. Trastuzumab (Herceptin; Genentech, South San Francisco, CA) is a monoclonal antibody targeting the HER2 extracellular domain that has been shown to significantly reduce relapse rates. However, some patients with HER2+ tumors do not respond to Herceptin, and 60% to 85% of patients with HER2+ metastatic breast cancer acquire resistance within a short time period. In this review, we discuss proposed mechanisms of action of trastuzumab and trastuzumab resistance and various drugs that have been developed to overcome drug resistance. We introduce the basal molecular subtype as a predictor of increased risk in HER2+ breast cancer and a possible alternative cause of drug resistance.
authors.affiliation: Department of Surgery, Division of Surgical Oncology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. alice.chung@cshs.org
authors.forename: Alice
authors.initials: A
authors.lastname: Chung
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Cui
authors.forename: William
authors.initials: W
authors.lastname: Audeh
authors.forename: Armando
authors.initials: A
authors.lastname: Giuliano
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
keywords: Basal molecular subtype; Her2-overexpressing breast cancer; Resistance; Trastuzumab (Herceptin)