title: Influence of the HER2 Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients: a meta-analysis.
abstract: BACKGROUND
  The HER2 655 A>G genetic variant has recently been associated with trastuzumab-induced cardiotoxicity in HER2 breast cancer patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the cardiac toxicity of trastuzumab in breast cancer patients.
  
  
  METHODS
  Our study population was composed of 78 HER2 breast cancer patients receiving trastuzumab. The HER2 655 A>G (rs1136201) genetic variant was genotyped using TaqMan allelic discrimination technology. Patients were classified on the basis of the occurrence of cardiotoxic events or the absence of cardiotoxic events during 1 year after the first infusion.
  
  
  RESULTS
  The HER2 655 A>G polymorphism was significantly associated with cardiotoxicity: AG versus AA [P=0.012, odds ratio (OR)=5.12, 95% confidence interval (CI) 1.43-18.36], AG+GG versus AA (P=0.01, OR=5.72, 95% CI 1.50-21.76), AG versus AA+GG (P=0.005, OR=7.17, 95% CI 1.82-28.29). A meta-analysis combining these data with the results from previous studies confirmed this association.
  
  
  CONCLUSIONS
  Our results support the role of the HER2 655 A>G polymorphism as a genetic marker of trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients.
authors.affiliation: aDepartment of Clinical Pharmacy bDepartment of Cardiology cDepartment of Oncology, San Cecilio University Hospital, Institute for biomedical research ibs.GRANADA dGenomic Unit eBioinformatics Unit, Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Granada fDepartment of Clinical Pharmacy, Torrecárdenas Hospital, Almería, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Gómez Peña
authors.forename: Cristina L
authors.initials: CL
authors.lastname: Dávila-Fajardo
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Martínez-González
authors.forename: Pedro
authors.initials: P
authors.lastname: Carmona-Sáez
authors.forename: María J
authors.initials: MJ
authors.lastname: Soto Pino
authors.forename: Jesús
authors.initials: J
authors.lastname: Sánchez Ramos
authors.forename: Eduardo
authors.initials: E
authors.lastname: Moreno Escobar
authors.forename: Isabel
authors.initials: I
authors.lastname: Blancas
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Fernández
authors.forename: Dámaso
authors.initials: D
authors.lastname: Fernández
authors.forename: Concepción
authors.initials: C
authors.lastname: Correa
authors.forename: José
authors.initials: J
authors.lastname: Cabeza Barrera
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D003710:Demography; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D000068878:Trastuzumab / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human