title: Benefit and projected cost-effectiveness of anastrozole versus tamoxifen as initial adjuvant therapy for patients with early-stage estrogen receptor-positive breast cancer.
abstract: BACKGROUND
  Women who have estrogen receptor (ER)-positive disease with postmenopausal onset and who receive tamoxifen as standard adjuvant treatment constitute the largest subgroup of patients with breast cancer. Recent data from the ATAC ('Arimidex, Tamoxifen Alone or in Combination') randomized trial indicate that anastrozole significantly reduces breast cancer recurrence rates but does not provide any advantage in terms of survival at 4 years posttreatment. Furthermore, anastrozole and tamoxifen were found to have different toxicity profiles. The goals of the current study were to estimate the disease-free survival (DFS) rates and potential survival benefits associated with anastrozole use and to determine whether the incremental cost-effectiveness (ICE) was low enough to warrant an immediate switch to the use of this agent, as the long-term conclusions of the ATAC trial will not be available for several years.
  
  
  METHODS
  A computer simulation model assessed the outcomes of 64-year-old women with ER-positive breast cancer who subsequently received either anastrozole or tamoxifen for 5 years. Daily recurrence risks, as well as the relative risks associated with various treatment-related events, were calculated using data from the ATAC trial. Study endpoints included breast cancer recurrence-free survival, anticipated survival resulting from an anastrozole-induced decrease in systemic disease recurrence rates, and survival adjusted for quality of life and for hip fracture risk over periods of 4, 12, and 20 years.
  
  
  RESULTS
  After 4 years, the projected DFS benefit associated with anastrozole was 14 days, with an ICE of $167,500 per year. Projected 12 and 20 years into the future, DFS benefits increased to 2.9 months and 5.3 months, respectively. The corresponding benefits in terms of overall survival were 0.9 months and 2.0 months, respectively, with the ICE becoming < $100,000 per life year once the projection horizon exceeded 12 years. The inclusion of quality-of-life weightings for nonfatal outcomes modestly favored anastrozole in the short term; however, if anastrozole use is associated with an increased risk of hip fracture, then the long-term benefit associated with this agent is reduced by approximately 25%.
  
  
  CONCLUSIONS
  Adjuvant anastrozole is projected to result in a substantial improvement in DFS for patients with breast cancer. If this DFS benefit were to ultimately lead to a survival benefit, then the ICE of anastrozole use would be acceptable for patients expected to live longer than 12 years. Decision models are useful for generating realistic projections for stakeholders who are considering competing options that impact survival and quality of life and have associated societal costs.
authors.affiliation: Department of Internal Medicine, Virginia Commonwealth University, Richmond 23298, USA. Hillner@mail2.vcu.edu
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Hillner
mesh_terms: D000368:Aged; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000191:economics* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003362:Cost-Benefit Analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D008962:Models, Theoretical; D009364:Neoplasm Recurrence, Local; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000191:economics; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D011960:Receptors, Estrogen / Q000378:metabolism*; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole