title: Efficacy, toxicity, and quality of life in older women with early-stage breast cancer treated with letrozole or placebo after 5 years of tamoxifen: NCIC CTG intergroup trial MA.17.
abstract: OBJECTIVE
  National Cancer Institute of Canada Clinical Trials Group trial MA.17 randomly assigned 5,187 postmenopausal, hormone-receptor-positive patients with early breast cancer who completed 5 years of tamoxifen to receive either letrozole or placebo. At 30 months median follow-up, letrozole significantly improved disease-free survival (DFS) in all patients and overall survival (OS) in node-positive patients. Breast cancer incidence increases with age and more than 1,300 women age 70 years or older were enrolled onto MA.17, making it ideal to explore the benefits, toxicities, and quality of life (QOL) impact of letrozole on older women.
  
  
  METHODS
  In this study, 5,169 randomly assigned patients were divided into three age groups: younger than 60 years (n = 2,152), 60 to 69 years (n = 1,694), and >or= 70 years (n = 1,323). Log-rank test was used to compare differences in DFS, distant-disease-free survival, and OS between age and treatment groups, and Cox models were used to estimate hazard ratios and associated 95% CIs. QOL was measured using the Medical Outcomes Short Form-36 and the Menopause-Specific Quality-of-Life questionnaire.
  
  
  RESULTS
  At 4 years, DFS demonstrated statistically significant differences favoring letrozole only in patients age younger than 60 years (hazard ratio = 0.46; P = .0004); there was no interaction between age and treatment, indicating a similar effect of letrozole among all age groups. There was no difference in toxicity or QOL at 24 months among letrozole- and placebo-treated patients age >or= 70 years.
  
  
  CONCLUSIONS
  Healthy patients age 70 years and older completing 5 years of tamoxifen should be considered for extended adjuvant therapy with letrozole.
authors.affiliation: University of Vermont College of Medicine, 1 South Prospect St, Saint Joseph 3400, Burlington, VT 05401, USA. hyman.muss@uvm.edu
authors.forename: Hyman B
authors.initials: HB
authors.lastname: Muss
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Robert
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Pater
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Whelan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Palmer
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Piccart
authors.forename: Lois E
authors.initials: LE
authors.lastname: Shepherd
authors.forename: Kathleen I
authors.initials: KI
authors.lastname: Pritchard
authors.forename: Zhi
authors.initials: Z
authors.lastname: He
authors.forename: Paul E
authors.initials: PE
authors.lastname: Goss
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects*; D010919:Placebos; D011788:Quality of Life; D013629:Tamoxifen / Q000008:administration & dosage*; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D010919:Placebos; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole