title: Intent-to-treat analysis of the placebo-controlled trial of letrozole for extended adjuvant therapy in early breast cancer: NCIC CTG MA.17.
abstract: BACKGROUND
  MA.17 evaluated letrozole or placebo after 5 years of tamoxifen and showed significant improvement in disease-free survival (DFS) for letrozole [hazard ratio (HR) 0.57, P = 0.00008]. The trial was unblinded and placebo patients were offered letrozole.
  
  
  METHODS
  An intent-to-treat analysis of all outcomes, before and after unblinding, on the basis of the original randomization was carried out.
  
  
  RESULTS
  In all, 5187 patients were randomly allocated to the study at baseline and, at unblinding, 1579 (66%) of 2383 placebo patients accepted letrozole. At median follow-up of 64 months (range 16-95), 399 recurrences or contralateral breast cancers (CLBCs) (164 letrozole and 235 placebo) occurred. Four-year DFS was 94.3% (letrozole) and 91.4% (placebo) [HR 0.68, 95% confidence interval (CI) 0.55-0.83, P = 0.0001] and showed superiority for letrozole in both node-positive and -negative patients. Corresponding 4-year distant DFS was 96.3% and 94.9% (HR 0.80, 95% CI 0.62-1.03, P = 0.082). Four-year overall survival was 95.1% for both groups. The annual rate of CLBC was 0.28% for letrozole and 0.46% for placebo patients (HR 0.61, 95% CI 0.39-0.97, P = 0.033).
  
  
  CONCLUSIONS
  Patients originally randomly assigned to receive letrozole within 3 months of stopping tamoxifen did better than placebo patients in DFS and CLBC, despite 66% of placebo patients taking letrozole after unblinding.
authors.affiliation: Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA. ingle.james@mayo.edu
authors.forename: J N
authors.initials: JN
authors.lastname: Ingle
authors.forename: D
authors.initials: D
authors.lastname: Tu
authors.forename: J L
authors.initials: JL
authors.lastname: Pater
authors.forename: H B
authors.initials: HB
authors.lastname: Muss
authors.forename: S
authors.initials: S
authors.lastname: Martino
authors.forename: N J
authors.initials: NJ
authors.lastname: Robert
authors.forename: M J
authors.initials: MJ
authors.lastname: Piccart
authors.forename: M
authors.initials: M
authors.lastname: Castiglione
authors.forename: L E
authors.initials: LE
authors.lastname: Shepherd
authors.forename: K I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: R B
authors.initials: RB
authors.lastname: Livingston
authors.forename: N E
authors.initials: NE
authors.lastname: Davidson
authors.forename: L
authors.initials: L
authors.lastname: Norton
authors.forename: E A
authors.initials: EA
authors.lastname: Perez
authors.forename: J S
authors.initials: JS
authors.lastname: Abrams
authors.forename: D A
authors.initials: DA
authors.lastname: Cameron
authors.forename: M J
authors.initials: MJ
authors.lastname: Palmer
authors.forename: P E
authors.initials: PE
authors.lastname: Goss
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004967:Estrogens; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077289:Letrozole; D008207:Lymphatic Metastasis; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D016609:Neoplasms, Second Primary / Q000188:drug therapy / Q000453:epidemiology; D009570:Nitriles / Q000008:administration & dosage / Q000627:therapeutic use*; D010342:Patient Acceptance of Health Care; D010919:Placebos; D017698:Postmenopause; D011374:Progesterone; D016016:Proportional Hazards Models; D012008:Recurrence; D013629:Tamoxifen / Q000627:therapeutic use; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004967:Estrogens; D009570:Nitriles; D010919:Placebos; D014230:Triazoles; D013629:Tamoxifen; D011374:Progesterone; D000077289:Letrozole