title: Neoadjuvant anastrozole versus tamoxifen in patients receiving goserelin for premenopausal breast cancer (STAGE): a double-blind, randomised phase 3 trial.
abstract: BACKGROUND
  Aromatase inhibitors have shown increased efficacy compared with tamoxifen in postmenopausal early breast cancer. We aimed to assess the efficacy and safety of anastrozole versus tamoxifen in premenopausal women receiving goserelin for early breast cancer in the neoadjuvant setting.
  
  
  METHODS
  In this phase 3, randomised, double-blind, parallel-group, multicentre study, we enrolled premenopausal women with oestrogen receptor (ER)-positive, HER2-negative, operable breast cancer with WHO performance status of 2 or lower. Patients were randomly assigned (1:1) to receive goserelin 3·6 mg/month plus either anastrozole 1 mg per day and tamoxifen placebo or tamoxifen 20 mg per day and anastrozole placebo for 24 weeks before surgery. Patients were randomised sequentially, stratified by centre, with randomisation codes. All study personnel were masked to study treatment. The primary endpoint was best overall tumour response (complete response or partial response), assessed by callipers, during the 24-week neoadjuvant treatment period for the intention-to-treat population. The primary endpoint was analysed for non-inferiority (with non-inferiority defined as the lower limit of the 95% CI for the difference in overall response rates between groups being 10% or less); in the event of non-inferiority, we assessed the superiority of the anastrozole group versus the tamoxifen group. We included all patients who received study medication at least once in the safety analysis set. We report the primary analysis; treatment will also continue in the adjuvant setting for 5 years. This trial is registered with ClinicalTrials.gov, number NCT00605267.
  
  
  RESULTS
  Between Oct 2, 2007, and May 29, 2009, 204 patients were enrolled. 197 patients were randomly assigned to anastrozole (n=98) or tamoxifen (n=99), and 185 patients completed the 24-week neoadjuvant treatment period and had breast surgery (95 in the anastrazole group, 90 in the tamoxifen group). More patients in the anastrozole group had a complete or partial response than did those in the tamoxifen group during 24 weeks of neoadjuvant treatment (anastrozole 70·4% [69 of 98 patients] vs tamoxifen 50·5% [50 of 99 patients]; estimated difference between groups 19·9%, 95% CI 6·5-33·3; p=0·004). Two patients in the anastrozole group had treatment-related grade 3 adverse events (arthralgia and syncope) and so did one patient in the tamoxifen group (depression). One serious adverse event was reported in the anastrozole group (benign neoplasm, not related to treatment), compared with none in the tamoxifen group.
  
  
  CONCLUSIONS
  Given its favourable risk-benefit profile, the combination of anastrozole plus goserelin could represent an alternative neoadjuvant treatment option for premenopausal women with early-stage breast cancer.
  
  
  BACKGROUND
  AstraZeneca.
authors.affiliation: National Hospital Organization, Osaka National Hospital, Osaka, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Masuda
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Sagara
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Hiroji
authors.initials: H
authors.lastname: Iwata
authors.forename: Seigo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yanagita
authors.forename: Reiki
authors.initials: R
authors.lastname: Nishimura
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwase
authors.forename: Shunji
authors.initials: S
authors.lastname: Kamigaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takei
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000328:Adult; D000077384:Anastrozole; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D005260:Female; D017273:Goserelin / Q000008:administration & dosage*; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000601:surgery; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects; D017697:Premenopause; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013629:Tamoxifen / Q000008:administration & dosage*; D014230:Triazoles / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000077384:Anastrozole; D047072:Aromatase Inhibitors; D017273:Goserelin; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; D014230:Triazoles; C508053:ERBB2 protein, human