title: Trastuzumab in the adjuvant treatment of early-stage breast cancer: a systematic review and meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  We performed a systematic review and meta-analysis to compare treatment outcomes for human epidermal growth factor receptor (HER)-2-positive breast cancer patients receiving adjuvant chemotherapy with or without trastuzumab.
  
  
  METHODS
  We identified randomized clinical trials comparing adjuvant chemotherapy with or without trastuzumab in patients with resectable breast cancer. Fixed-effects meta-analysis was used to combine data.
  
  
  RESULTS
  Five eligible trials were identified, reporting outcomes on 13,493 women. Fixed-effects analysis showed disease-free survival to be superior for trastuzumab-treated patients (risk ratio [RR], 0.62; 95% confidence interval [CI], 0.56-0.68). Superiority was also observed for patients receiving trastuzumab with respect to mortality (RR, 0.66; 95% CI, 0.57-0.77), locoregional recurrence (RR, 0.58; 95% CI, 0.43-0.77), and distant recurrence (RR, 0.60; 95% CI, 0.52-0.68). Patients receiving trastuzumab with chemotherapy had a higher risk for congestive heart failure (RR, 7.60; 95% CI, 4.07-14.18) and left ventricular ejection fraction decline (RR, 2.09; 95% CI, 1.84-2.37). A higher risk for central nervous system metastasis as the first recurrence event (RR, 1.60; 95% CI, 1.06-2.40) was also noted in patients receiving trastuzumab.
  
  
  CONCLUSIONS
  The use of trastuzumab should be considered an integral part of the adjuvant therapy of HER-2-positive breast cancer patients.
authors.affiliation: Department of Molecular Biology and Genetics, Metropolitan Hospital, 1, Ethnarhou Makariou & Venizelou Street, Piraeus, Greece.
authors.forename: Issa J
authors.initials: IJ
authors.lastname: Dahabreh
authors.forename: Helen
authors.initials: H
authors.lastname: Linardou
authors.forename: Fotios
authors.initials: F
authors.lastname: Siannis
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
authors.forename: Samuel
authors.initials: S
authors.lastname: Murray
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007124:Immunoenzyme Techniques; D009367:Neoplasm Staging; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human