title: Human epidermal growth factor antagonists and cardiotoxicity-A short review of the problem and preventative measures.
abstract: The Human Epidermal growth factor Receptor 2 (HER2) is a potent mediator of cellular growth and proliferation. It plays an important role in cardiac development and maintaining the physiologic function of an adult heart. Amplification of the HER2 gene, and the corresponding overexpression of the HER2 receptor, occurs in roughly 20% of breast tumors and is associated with a poor outcome. Molecular targeting of the HER2 receptor with the humanized monoclonal antibody, Trastuzumab has improved disease-free and overall survival in patients with both metastatic and early HER2-positive breast cancer. Although trastuzumab is devoid of the classical toxicities associated with chemotherapy, one of the major concerns noted is the occurrence of symptomatic and asymptomatic cardiotoxicity (decline in left-ventricular-ejection-fraction (LVEF). Additionally, newer HER2 therapies such as Lapatinib, Pertuzumab and Ado-trastuzumab (TDM1) are either approved or are being evaluated in clinical trials for cancer therapy. Targeted therapies against HER2 have led to revolutionary strides in breast cancer research and treatment. With the concern of cardiotoxicity caused by these agents, new treatment strategies for preventing cardiac side effects need to be developed. In this review, we discuss the proposed mechanisms of HER 2 antagonist-induced cardiotoxicity and the ways to prevent it.
authors.affiliation: Division of Hematology and Medical Oncology, James Graham Brown Cancer Center, University of Louisville Health Sciences Center, Louisville, KY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Dias
authors.affiliation: Division of Hematology and Medical Oncology, James Graham Brown Cancer Center, University of Louisville Health Sciences Center, Louisville, KY, USA.
authors.forename: W
authors.initials: W
authors.lastname: Claudino
authors.affiliation: Department of Internal Medicine, University of Louisville Health Sciences Center, Louisville, KY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Division of Hematology and Medical Oncology, James Graham Brown Cancer Center, University of Louisville Health Sciences Center, Louisville, KY, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Perez
authors.affiliation: Division of Hematology and Medical Oncology, James Graham Brown Cancer Center, University of Louisville Health Sciences Center, Louisville, KY, USA. Electronic address: d0jain01@louisville.edu.
authors.forename: D
authors.initials: D
authors.lastname: Jain
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D066126:Cardiotoxicity; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors*; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004815:Epidermal Growth Factor
keywords: Ado-trastuzumab (T-DM1); Human epidermal receptor 2 (HER2); Lapatinib; Left ventricular ejection fraction (LVEF); Pertuzumab; Trastuzumab