title: Trastuzumab cardiotoxicity: from clinical trials to experimental studies.
abstract: Epidermal growth factor receptor-2 (HER-2) is overexpressed in 20 to 25% of human breast cancers, which is associated with aggressive tumour growth and poor prognosis. Trastuzumab (Herceptin®) is a humanized monoclonal antibody directed against HER-2, the first highly selective form of therapy targeting HER-2 overexpressing tumours. Although initial trials indicated high efficacy and a favourable safety profile of the drug, the first large, randomized trial prompted a retrospective analysis of cardiac dysfunction in earlier trials utilizing trastuzumab. There has been ongoing debate on the cardiac safety of trastuzumab ever since, initiating numerous clinical and preclinical investigations to better understand the background of trastuzumab cardiotoxicity and evaluate its effects on patient morbidity. Here, we have given a comprehensive overview of our current knowledge on the cardiotoxicity of trastuzumab, primarily focusing on data from clinical trials and highlighting the main molecular mechanisms proposed.
  
  
  BACKGROUND
  This article is part of a themed section on New Insights into Cardiotoxicity Caused by Chemotherapeutic Agents. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.21/issuetoc.
authors.affiliation: Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA.
authors.forename: Balazs T
authors.initials: BT
authors.lastname: Nemeth
authors.affiliation: Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA.
authors.forename: Zoltan V
authors.initials: ZV
authors.lastname: Varga
authors.affiliation: Division of Biotechnology Research and Review 1, Office of Biotechnology Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD, USA.
authors.forename: Wen Jin
authors.initials: WJ
authors.lastname: Wu
authors.affiliation: Laboratory of Cardiovascular Physiology and Tissue Injury, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA.
authors.forename: Pal
authors.initials: P
authors.lastname: Pacher
mesh_terms: D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy; D066126:Cardiotoxicity / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000074322:Antineoplastic Agents, Immunological; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human