title: Economic evaluation of genomic test-directed chemotherapy for early-stage lymph node-positive breast cancer.
abstract: BACKGROUND
  Multi-parameter genomic tests identify patients with early-stage breast cancer who are likely to derive little benefit from adjuvant chemotherapy. These tests can potentially spare patients the morbidity from unnecessary chemotherapy and reduce costs. However, the costs of the test must be balanced against the health benefits and cost savings produced. This economic evaluation compared genomic test-directed chemotherapy using the Oncotype DX 21-gene assay with chemotherapy for all eligible patients with lymph node-positive, estrogen receptor-positive early-stage breast cancer.
  
  
  METHODS
  We performed a cost-utility analysis using a state transition model to calculate expected costs and benefits over the lifetime of a cohort of women with estrogen receptor-positive lymph node-positive breast cancer from a UK perspective. Recurrence rates for Oncotype DX-selected risk groups were derived from parametric survival models fitted to data from the Southwest Oncology Group 8814 trial. The primary outcome was the incremental cost-effectiveness ratio, expressed as the cost (in 2011 GBP) per quality-adjusted life-year (QALY). Confidence in the incremental cost-effectiveness ratio was expressed as a probability of cost-effectiveness and was calculated using Monte Carlo simulation. Model parameters were varied deterministically and probabilistically in sensitivity analysis. Value of information analysis was used to rank priorities for further research.
  
  
  RESULTS
  The incremental cost-effectiveness ratio for Oncotype DX-directed chemotherapy using a recurrence score cutoff of 18 was £5529 (US $8852) per QALY. The probability that test-directed chemotherapy is cost-effective was 0.61 at a willingness-to-pay threshold of £30 000 per QALY. Results were sensitive to the recurrence rate, long-term anthracycline-related cardiac toxicity, quality of life, test cost, and the time horizon. The highest priority for further research identified by value of information analysis is the recurrence rate in test-selected subgroups.
  
  
  CONCLUSIONS
  There is substantial uncertainty regarding the cost-effectiveness of Oncotype DX-directed chemotherapy. It is particularly important that future research studies to inform cost-effectiveness-based decisions collect long-term outcome data.
authors.affiliation: Academic Unit of Health Economics, Leeds Institute of Health Sciences, University of Leeds, UK. p.s.hall@leeds.ac.uk
authors.forename: Peter S
authors.initials: PS
authors.lastname: Hall
authors.forename: Christopher
authors.initials: C
authors.lastname: McCabe
authors.forename: Robert C
authors.initials: RC
authors.lastname: Stein
authors.forename: David
authors.initials: D
authors.lastname: Cameron
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000191:economics* / Q000627:therapeutic use*; D001499:Bayes Theorem; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000191:economics* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D015986:Confounding Factors, Epidemiologic; D003362:Cost-Benefit Analysis; D016527:Drug Costs; D005260:Female; D005820:Genetic Testing / Q000191:economics*; D015894:Genome, Human; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008390:Markov Chains; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009313:National Health Programs / Q000941:ethics; D009367:Neoplasm Staging; D019057:Quality-Adjusted Life Years; D011960:Receptors, Estrogen / Q000032:analysis; D012107:Research Design; D018570:Risk Assessment / Q000379:methods; D006113:United Kingdom
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen