title: Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group.
abstract: OBJECTIVE
  Anastrozole (ANA) alone delivers significant disease-free survival benefits over tamoxifen (TAM) monotherapy in postmenopausal women with early estrogen receptor-positive breast cancer. The ABCSG-8 (Austrian Breast and Colorectal Cancer Study Group 8) study is a large phase III clinical trial addressing the sequence strategy containing ANA in comparison with 5 years of TAM in a low- to intermediate-risk group of postmenopausal patients.
  
  
  METHODS
  Endocrine receptor-positive patients with G1 or G2 tumors were eligible. After surgery, patients were randomly assigned to 5 years of TAM or 2 years of TAM followed by 3 years of ANA. Adjuvant chemotherapy and G3 and T4 tumors were exclusion criteria. Intention-to-treat and censored analyses of on-treatment recurrence-free survival (RFS) were performed, and exploratory survival end points and toxicity were investigated.
  
  
  RESULTS
  Information from 3,714 patients, including 17,563 woman-years, with a median of 60 months of follow-up was available for this analysis. Median age was 63.8 years, 75% were node negative, and 75% had T1 tumors. Sequencing of ANA after identical 2-year treatment with TAM in both arms did not result in a statistically significant improvement of RFS (hazard ratio [HR], 0.80; 95% CI, 0.63 to 1.01; P = .06). Exploratory analyses of distant relapse-free survival indicated a 22% improvement (HR, 0.78; 95% CI, 0.60 to 1.00). On-treatment adverse events and serious adverse events were consistent with known toxicity profiles of ANA and TAM treatment.
  
  
  CONCLUSIONS
  Despite a low overall rate of recurrence in a population with breast cancer at limited risk of relapse, the a priori sequence strategy of 2 years of TAM followed by 3 years of ANA led to small outcome and toxicity benefits.
authors.affiliation: Medical University of Vienna, Austria.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Dubsky
authors.forename: Raimund
authors.initials: R
authors.lastname: Jakesz
authors.forename: Brigitte
authors.initials: B
authors.lastname: Mlineritsch
authors.forename: Sabine
authors.initials: S
authors.lastname: Pöstlberger
authors.forename: Hellmut
authors.initials: H
authors.lastname: Samonigg
authors.forename: Werner
authors.initials: W
authors.lastname: Kwasny
authors.forename: Christoph
authors.initials: C
authors.lastname: Tausch
authors.forename: Herbert
authors.initials: H
authors.lastname: Stöger
authors.forename: Karin
authors.initials: K
authors.lastname: Haider
authors.forename: Florian
authors.initials: F
authors.lastname: Fitzal
authors.forename: Christian F
authors.initials: CF
authors.lastname: Singer
authors.forename: Michael
authors.initials: M
authors.lastname: Stierer
authors.forename: Paul
authors.initials: P
authors.lastname: Sevelda
authors.forename: Gero
authors.initials: G
authors.lastname: Luschin-Ebengreuth
authors.forename: Susanne
authors.initials: S
authors.lastname: Taucher
authors.forename: Margaretha
authors.initials: M
authors.lastname: Rudas
authors.forename: Rupert
authors.initials: R
authors.lastname: Bartsch
authors.forename: Günther G
authors.initials: GG
authors.lastname: Steger
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.forename: Lidija
authors.initials: L
authors.lastname: Filipcic
authors.forename: Michael
authors.initials: M
authors.lastname: Gnant
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001317:Austria; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D015996:Survival Rate; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole