title: Prognostic relevance of receptor tyrosine kinase expression in breast cancer: a meta-analysis.
abstract: BACKGROUND
  Receptor tyrosine kinases (RTKs) may facilitate tumor progression if activated aberrantly. The prognostic impact of human epidermal growth factor receptor 2 (HER2) overexpression and effectiveness of its therapeutic targeting is well established, but the effects on prognosis of overexpression of other RTKs is unknown. Here we evaluate the association of RTK expression and survival in breast cancer.
  
  
  METHODS
  PubMed was searched to identify studies evaluating the association between expression of RTKs other than HER2 and survival of women with breast cancer. Published data were extracted and computed into odds ratios (OR) for death at 5 years with 95% confidence intervals (CI). Data were pooled in a meta-analysis using the Mantel-Haenszel random-effect model. For studies reporting data for more than one RTK the lowest and highest OR were used for separate analyses.
  
  
  RESULTS
  Sixteen studies comprising 11,056 patients were included in the analysis. There was an association between overexpression of RTKs and decreased 5-year OS and this was highly significant when using highest ORs from studies reporting more than one RTK (OR=2.42; 95% CI=1.92-3.06, P<0.001). Similar results were observed for 5-year BCSS. Worse OS was seen with overexpression of fibroblast growth factor receptor 2/3 (FGFR) (OR=3.81; 95% CI=1.79-8.11) and epidermal growth factor receptor (EGFR)/HER1 (OR=2.45; 95% CI=1.90-3.15).
  
  
  CONCLUSIONS
  Overexpression of various RTKs is associated with poor outcomes. This data suggests the clinical evaluation of combination of agents against RTKs or relevant oncogenic nodes.
authors.affiliation: Divisions of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Arnoud J
authors.initials: AJ
authors.lastname: Templeton
authors.affiliation: Translational Oncology Unit, Albacete University Hospital, Albacete, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Diez-Gonzalez
authors.affiliation: Divisions of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Olga
authors.initials: O
authors.lastname: Ace
authors.affiliation: Divisions of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Francisco
authors.initials: F
authors.lastname: Vera-Badillo
authors.affiliation: Department of Medical Oncology, Institute of Oncology Ljubljana, Slovenia.
authors.forename: Boštjan
authors.initials: B
authors.lastname: Seruga
authors.affiliation: Translational Oncology Unit, Albacete University Hospital, Albacete, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Jordán
authors.affiliation: Divisions of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Eitan
authors.initials: E
authors.lastname: Amir
authors.affiliation: IBMCC-CSIC, Universidad de Salamanca, Spain.
authors.forename: Atanasio
authors.initials: A
authors.lastname: Pandiella
authors.affiliation: Translational Oncology Unit, Albacete University Hospital, Albacete, Spain. Electronic address: albertoo@sescam.jccm.es.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ocaña
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000378:metabolism
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors; C496353:FGFR2 protein, human; C496365:FGFR3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3
keywords: Breast cancer; Meta-analysis; Overexpression; Prognosis; Receptor tyrosine kinase; Targeted therapy