title: Impact of premenopausal status at breast cancer diagnosis in women entered on the placebo-controlled NCIC CTG MA17 trial of extended adjuvant letrozole.
abstract: BACKGROUND
  MA17 showed improved outcomes in postmenopausal women given extended letrozole (LET) after completing 5 years of adjuvant tamoxifen.
  
  
  METHODS
  Exploratory subgroup analyses of disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), toxic effects and quality of life (QOL) in MA17 were performed based on menopausal status at breast cancer diagnosis.
  
  
  RESULTS
  At diagnosis, 877 women were premenopausal and 4289 were postmenopausal. Extended LET was significantly better than placebo (PLAC) in DFS for premenopausal [hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.13-0.55; P = 0.0003] and postmenopausal women (HR = 0.67; 95% CI 0.51-0.89; P = 0.006), with greater DFS benefit in those premenopausal (interaction P = 0.03). In adjusted post-unblinding analysis, those who switched from PLAC to LET improved DDFS in premenopausal (HR = 0.15; 95% CI 0.03-0.79; P = 0.02) and postmenopausal women (HR = 0.45; 95% CI 0.22-0.94; P = 0.03).
  
  
  CONCLUSIONS
  Extended LET after 5 years of tamoxifen was effective in pre- and postmenopausal women at diagnosis, and significantly better in those premenopausal. Women premenopausal at diagnosis should be considered for extended adjuvant therapy with LET if menopausal after completing tamoxifen.
authors.affiliation: Cancer Center, Massachusetts General Hospital, Boston. Electronic address: pgoss@partners.org.
authors.forename: P E
authors.initials: PE
authors.lastname: Goss
authors.affiliation: Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester.
authors.forename: J N
authors.initials: JN
authors.lastname: Ingle
authors.affiliation: Breast Cancer Division, Los Angeles Clinic and Research Institute, Santa Monica.
authors.forename: S
authors.initials: S
authors.lastname: Martino
authors.affiliation: Virgina Cancer Specialists, Inova Fairfax Hospital, Virgina.
authors.forename: N J
authors.initials: NJ
authors.lastname: Robert
authors.affiliation: Department of Medicine and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill.
authors.forename: H B
authors.initials: HB
authors.lastname: Muss
authors.affiliation: University of Washington, Seattle.
authors.forename: R B
authors.initials: RB
authors.lastname: Livingston
authors.affiliation: Cancer Institute and UPMC Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh.
authors.forename: N E
authors.initials: NE
authors.lastname: Davidson
authors.affiliation: Mayo Clinic Cancer Center, Jacksonville, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Perez
authors.affiliation: Cancer Center, Massachusetts General Hospital, Boston.
authors.forename: Y
authors.initials: Y
authors.lastname: Chavarri-Guerra
authors.affiliation: Edinburgh Breast Unit, Western General Hospital and, University of Edinburgh, Edinburgh, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Cameron
authors.affiliation: Sunnybrook Odette Regional Cancer Centre, University of Toronto, Toronto.
authors.forename: K I
authors.initials: KI
authors.lastname: Pritchard
authors.affiliation: Department of Oncology, McMaster University, Hamilton.
authors.forename: T
authors.initials: T
authors.lastname: Whelan
authors.affiliation: National Cancer Institute of Canada, Clinical Trials Group, Kingston, Canada.
authors.forename: L E
authors.initials: LE
authors.lastname: Shepherd
authors.affiliation: National Cancer Institute of Canada, Clinical Trials Group, Kingston, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Tu
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D017698:Postmenopause; D017697:Premenopause; D011788:Quality of Life; D013534:Survival; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D009570:Nitriles; D010919:Placebos; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole