title: Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen.
abstract: OBJECTIVE
  The National Cancer Institute of Canada Clinical Trials Group MA.17 trial examined the efficacy of letrozole (LET) started within 3 months of 5 years of adjuvant tamoxifen in postmenopausal hormone receptor-positive early-stage breast cancer. When the trial was unblinded, patients who received placebo (PLAC) were offered LET.
  
  
  METHODS
  This cohort analysis describes the outcomes of women assigned PLAC at the initial random assignment after unblinding. Efficacy outcomes of women who chose LET (PLAC-LET group) were compared with those who did not (PLAC-PLAC group) by the hazard ratios and by P values calculated from Cox models that adjusted for imbalances between the groups. Toxicity analyses included only events that occurred after unblinding.
  
  
  RESULTS
  There were 1,579 women in the PLAC-LET group (median time from tamoxifen, 2.8 years) and 804 in the PLAC-PLAC group. Patients in the PLAC-LET group were younger; had a better performance status; and were more likely to have had node-positive disease, axillary dissection, and adjuvant chemotherapy than those in the PLAC-PLAC group. At a median follow-up of 5.3 years, disease-free survival (DFS; adjusted hazard ratio [HR], 0.37; 95% CI, 0.23 to 0.61; P < .0001) and distant DFS (HR, 0.39; 95% CI, 0.20 to 0.74; P = .004) were superior in the PLAC-LET group. More self-reported new diagnoses of osteoporosis and significantly more clinical fractures occurred in the women who took LET (5.2% v 3.1%, P = .02).
  
  
  CONCLUSIONS
  Interpretation of this cohort analysis suggests that LET improves DFS and distant DFS even when there has been a substantial period of time since the discontinuation of prior adjuvant tamoxifen.
authors.affiliation: Massachusetts General Hospital Cancer Center, 55 Fruit St, Lawrence House, LRH-302, Boston, MA 02114, USA. pgoss@partners.org
authors.forename: Paul E
authors.initials: PE
authors.lastname: Goss
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Pater
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Robert
authors.forename: Hyman B
authors.initials: HB
authors.lastname: Muss
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Piccart
authors.forename: Monica
authors.initials: M
authors.lastname: Castiglione
authors.forename: Lois E
authors.initials: LE
authors.lastname: Shepherd
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: Robert B
authors.initials: RB
authors.lastname: Livingston
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Abrams
authors.forename: David A
authors.initials: DA
authors.lastname: Cameron
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Palmer
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects; D010919:Placebos; D017698:Postmenopause; D013629:Tamoxifen / Q000008:administration & dosage*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D009570:Nitriles; D010919:Placebos; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole