title: Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen.
abstract: OBJECTIVE
  To conduct meta-analyses of randomized trials of aromatase inhibitors (AIs) compared with tamoxifen either as initial monotherapy (cohort 1) or after 2 to 3 years of tamoxifen (cohort 2).
  
  
  METHODS
  Data submitted to the Early Breast Cancer Trialists' Collaborative Group were used in separate meta-analyses of two cohorts. Primary analyses involve postmenopausal women with tumors reported to be estrogen receptor positive. Log-rank P values are two-sided.
  
  
  RESULTS
  Cohort 1 comprised 9,856 patients with a mean of 5.8 years of follow-up. At 5 years, AI therapy was associated with an absolute 2.9% (SE = 0.7%) decrease in recurrence (9.6% for AI v 12.6% for tamoxifen; 2P < .00001) and a nonsignificant absolute 1.1% (SE = 0.5%) decrease in breast cancer mortality (4.8% for AI v 5.9% for tamoxifen; 2P = .1). Cohort 2 comprised 9,015 patients with a mean of 3.9 years of follow-up. At 3 years from treatment divergence (ie, approximately 5 years after starting hormonal treatment), AI therapy was associated with an absolute 3.1% (SE = 0.6%) decrease in recurrence (5.0% for AI v 8.1% for tamoxifen since divergence; 2P < .00001) and an absolute 0.7% (SE = 0.3%) decrease in breast cancer mortality (1.7% for AI v 2.4% for tamoxifen since divergence; 2P = .02). There was no convincing heterogeneity in the proportional recurrence reduction with respect to age, nodal status, tumor grade, or progesterone receptor status and no indication of an increase in nonbreast deaths with AIs in either cohort. CONCLUSION AIs produce significantly lower recurrence rates compared with tamoxifen, either as initial monotherapy or after 2 to 3 years of tamoxifen. Additional follow-up will provide clearer information on long-term survival.
authors: Academic Department of Biochemistry, Royal Marsden Hospital, London, United Kingdom. mitch.dowsett@icr.ac.uk
authors: Mitch
authors: M
authors: Dowsett
authors: Jack
authors: J
authors: Cuzick
authors: Jim
authors: J
authors: Ingle
authors: Alan
authors: A
authors: Coates
authors: John
authors: J
authors: Forbes
authors: Judith
authors: J
authors: Bliss
authors: Marc
authors: M
authors: Buyse
authors: Michael
authors: M
authors: Baum
authors: Aman
authors: A
authors: Buzdar
authors: Marco
authors: M
authors: Colleoni
authors: Charles
authors: C
authors: Coombes
authors: Claire
authors: C
authors: Snowdon
authors: Michael
authors: M
authors: Gnant
authors: Raimund
authors: R
authors: Jakesz
authors: Manfred
authors: M
authors: Kaufmann
authors: Francesco
authors: F
authors: Boccardo
authors: Jon
authors: J
authors: Godwin
authors: Christina
authors: C
authors: Davies
authors: Richard
authors: R
authors: Peto
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D013629:Tamoxifen