title: Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial.
abstract: BACKGROUND
  Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease.
  
  
  METHODS
  Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319.
  
  
  RESULTS
  1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0-7·1), 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio 0·47, 95% CI 0·32-0·68, p<0·0001). The predicted cumulative incidence of all breast cancers after 7 years was 5·6% in the placebo group and 2·8% in the anastrozole group. 18 deaths were reported in the anastrozole group and 17 in the placebo group, and no specific causes were more common in one group than the other (p=0·836).
  
  
  CONCLUSIONS
  Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer.
  
  
  BACKGROUND
  Cancer Research UK, the National Health and Medical Research Council Australia, Sanofi-Aventis, and AstraZeneca.
authors: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK. Electronic address: j.cuzick@qmul.ac.uk.
authors: Jack
authors: J
authors: Cuzick
authors: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
authors: Ivana
authors: I
authors: Sestak
authors: Australian New Zealand Breast Cancer Trials Group, Calvary Mater Newcastle, University of Newcastle, Waratah, NSW, Australia.
authors: John F
authors: JF
authors: Forbes
authors: Academic Department of Biochemistry, The Royal Marsden NHS Trust, London, UK.
authors: Mitch
authors: M
authors: Dowsett
authors: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
authors: Jill
authors: J
authors: Knox
authors: Breast Care Centre, Southmead Hospital, Bristol, UK.
authors: Simon
authors: S
authors: Cawthorn
authors: University of Western Australia, Crawley, WA, Australia.
authors: Christobel
authors: C
authors: Saunders
authors: Breast Unit, The Royal Marsden NHS Trust, London, UK.
authors: Nicola
authors: N
authors: Roche
authors: Department of Surgery, University of Wales College of Medicine, Cardiff, UK.
authors: Robert E
authors: RE
authors: Mansel
authors: German Breast Group, Neu-Isenburg, Germany; University Women's Hospital, Frankfurt, Germany.
authors: Gunter
authors: G
authors: von Minckwitz
authors: Division of Chemoprevention and Genetics, European Institute of Oncology, Milan, Italy.
authors: Bernardo
authors: B
authors: Bonanni
authors: Pirkanmaa Cancer Society, Tampere, Finland.
authors: Tiina
authors: T
authors: Palva
authors: Genesis Breast Cancer Prevention Centre, Manchester, UK.
authors: Anthony
authors: A
authors: Howell
mesh_terms: D000328:Adult; D000368:Aged; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000517:prevention & control*; D018270:Carcinoma, Ductal, Breast / Q000517:prevention & control*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000517:prevention & control*; D018275:Carcinoma, Lobular / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D017698:Postmenopause; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole