title: Testing for HER2-positive breast cancer: a systematic review and cost-effectiveness analysis.
abstract: BACKGROUND
  Testing to determine HER2 status has come into focus since the approval of trastuzumab (Herceptin) for the treatment of HER2-positive breast cancer. We compared the cost-effectiveness of various strategies used to test HER2 status, an important first step toward evaluating the overall cost-effectiveness of trastuzumab therapy.
  
  
  METHODS
  We performed a systematic review of studies that evaluated concordance between immunohistochemistry and fluorescence in situ hybridization testing to determine HER2 status. We performed a meta-analysis to estimate the distribution of immunohistochemistry scores in each category (0, 1+, 2+, 3+) and the probability of receiving a positive result of fluorescence in situ hybridization (which we assumed to be the "gold-standard" test) for each category. We calculated the accuracy and incremental cost per accurate diagnosis for each testing strategy compared with the base strategy (immunohistochemistry testing, followed by confirmation of 2+ scores by fluorescence in situ hybridization).
  
  
  RESULTS
  The median percentage of patients in each category of immunohistochemistry score was: 0, 36.1%; 1+, 35.5%; 2+, 12.0%; and 3+, 16.2%. The median percentage of results of fluorescence in situ hybridization that were positive in each immunohistochemistry category was: 0, 1.6%; 1+, 4.9%; 2+, 29.8%; and 3+, 92.4%. The base strategy was expected to correctly determine the HER2 status of 96% of patients with breast cancer. Confirmation of the HER2 status by fluorescence in situ hybridization in cases that received a score of 3+ reduced the percentage of false-positive results to 0% and increased the percentage of accurately determined HER2 results to 97.6%. Compared with the base strategy, this strategy was associated with a median incremental cost-effectiveness ratio of $6175 per case of accurately determined HER2 status. The strategy of performing fluorescence in situ hybridization testing in all cases of breast cancer was associated with a median incremental cost-effectiveness ratio of $8401 per case of accurately determined HER2 status.
  
  
  CONCLUSIONS
  The strategy with the lowest cost-effectiveness ratio involved screening all newly diagnosed cases of breast cancer with immunohistochemistry and confirming scores of 2+ or 3+ with fluorescence in situ hybridization testing.
authors.affiliation: Technology Assessment Unit, McGill University Health Centre, Montréal, Que. nandini.dendukuri@mcgill.ca
authors.forename: Nandini
authors.initials: N
authors.lastname: Dendukuri
authors.forename: Karim
authors.initials: K
authors.lastname: Khetani
authors.forename: Michelle
authors.initials: M
authors.lastname: McIsaac
authors.forename: James
authors.initials: J
authors.lastname: Brophy
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D002170:Canada; D003362:Cost-Benefit Analysis; D005189:False Positive Reactions; D005260:Female; D018734:Genes, erbB-2; D005820:Genetic Testing / Q000191:economics* / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry / Q000191:economics / Q000379:methods; D012680:Sensitivity and Specificity