title: Extended adjuvant tamoxifen for early breast cancer: a meta-analysis.
abstract: BACKGROUND
  Hormone receptor positive breast cancer is characterized by the potential for disease recurrence many years after initial diagnosis. Endocrine therapy has been shown to reduce the risk of such recurrence, but the optimal duration of endocrine therapy remains unclear.
  
  
  METHODS
  We conducted a systematic review and meta-analysis to quantify the benefits and harms of extended adjuvant tamoxifen (>5 years of therapy) compared with adjuvant tamoxifen (5 years of therapy). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for disease recurrence, death and adverse events. Subgroup analyses by timing of recurrence and baseline lymph node and menopause status were carried.
  
  
  RESULTS
  Five trials comprising 21,554 patients were included. Extended adjuvant tamoxifen was not associated with a significant reduction in the risk of recurrence (OR:0.89, 95% CI 0.76-1.05, p = 0.17). There was no association between extended adjuvant tamoxifen and all-cause death (OR:0.99, 95% CI 0.84-1.16, p = 0.88). There was an apparent reduction in risk of recurrence occurring after completion of extended adjuvant tamoxifen with little evidence of effect during therapy, however, this difference was not significant (p for difference 0.10). Subgroup analysis suggested that a greater effect size among lymph node positive patients compared with those who are lymph node negative (NNT: 25 vs. 49). There was no apparent difference in the effect between pre- and post-menopausal patients. Endometrial carcinoma was substantially more frequent with extended adjuvant tamoxifen (OR:2.06, 95% CI 1.65-2.58, p<0.001, number needed to harm:89).
  
  
  CONCLUSIONS
  In unselected patients, extended adjuvant tamoxifen is not associated with a significant reduction in recurrence, or a reduction in all-cause death. Patients with lymph node positive breast cancer may derive some benefit. Reduction in the risk of recurrence appears to occur only after completion of extended adjuvant therapy.
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, Canada ; Ministry of Higher Education, Riyadh, Saudi Arabia.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Al-Mubarak
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Ariadna
authors.initials: A
authors.lastname: Tibau
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Arnoud J
authors.initials: AJ
authors.lastname: Templeton
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: David W
authors.initials: DW
authors.lastname: Cescon
authors.affiliation: Medical Oncology Department and Translational Research Unit, Albacete University Hospital, Albacete, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ocana
authors.affiliation: Sector of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Bostjan
authors.initials: B
authors.lastname: Seruga
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre and Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Eitan
authors.initials: E
authors.lastname: Amir
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D008593:Menopause / Q000502:physiology; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D016017:Odds Ratio; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D013629:Tamoxifen