title: Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group.
abstract: OBJECTIVE
  To analyze overall survival (OS) and update efficacy data for letrozole versus tamoxifen as first-line therapy in postmenopausal women with locally advanced or metastatic breast cancer.
  
  
  METHODS
  This multicenter phase III trial randomly assigned 916 patients with hormone receptor-positive or unknown tumors letrozole 2.5 mg (n = 458) or tamoxifen 20 mg (n = 458) daily until disease progression. Optional cross-over was permitted at the treating physician's discretion. This report updates efficacy at a median follow-up of 32 months.
  
  
  RESULTS
  The superiority of letrozole to tamoxifen was confirmed for time to progression (median, 9.4 v 6.0 months, respectively; P <.0001), time to treatment failure (median, 9 v 5.7 months, respectively; P <.0001), overall objective response rate (32% v 21%, respectively; P =.0002), and overall clinical benefit. Median OS was slightly prolonged for the randomized letrozole arm (34 v 30 months, respectively). Although this difference in OS is not significant, survival was improved in the randomized letrozole arm over the first 2 years of the study. Approximately one half of the patients in each arm crossed over. Total duration of endocrine therapy ("time to chemotherapy") was significantly longer (P =.005) for patients initially on letrozole (median, 16 months) than for patients initially on tamoxifen (median, 9 months). Time to worsening of Karnofsky performance score was significantly delayed with letrozole compared with tamoxifen (P =.001).
  
  
  CONCLUSIONS
  This study documents the superiority of letrozole over tamoxifen in first-line endocrine therapy in postmenopausal women with advanced breast cancer.
authors.affiliation: Rigshospitalet, Copenhagen, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Mouridsen
authors.forename: Mikhail
authors.initials: M
authors.lastname: Gershanovich
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Ramon
authors.initials: R
authors.lastname: Perez-Carrion
authors.forename: Corrado
authors.initials: C
authors.lastname: Boni
authors.forename: Alain
authors.initials: A
authors.lastname: Monnier
authors.forename: Justus
authors.initials: J
authors.lastname: Apffelstaedt
authors.forename: Robert
authors.initials: R
authors.lastname: Smith
authors.forename: Harm P
authors.initials: HP
authors.lastname: Sleeboom
authors.forename: Fritz
authors.initials: F
authors.lastname: Jaenicke
authors.forename: Anna
authors.initials: A
authors.lastname: Pluzanska
authors.forename: Magdolna
authors.initials: M
authors.lastname: Dank
authors.forename: Dominique
authors.initials: D
authors.lastname: Becquart
authors.forename: Poonamalle P
authors.initials: PP
authors.lastname: Bapsy
authors.forename: Eeva
authors.initials: E
authors.lastname: Salminen
authors.forename: Ray
authors.initials: R
authors.lastname: Snyder
authors.forename: Hilary
authors.initials: H
authors.lastname: Chaudri-Ross
authors.forename: Raquel
authors.initials: R
authors.lastname: Lang
authors.forename: Peter
authors.initials: P
authors.lastname: Wyld
authors.forename: Ajay
authors.initials: A
authors.lastname: Bhatnagar
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018592:Cross-Over Studies; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D017698:Postmenopause; D016016:Proportional Hazards Models; D015996:Survival Rate; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole