title: Genomic tests for ovarian cancer detection and management.
abstract: OBJECTIVE
  To assess the evidence that the use of genomic tests for ovarian cancer screening, diagnosis, and treatment leads to improved outcomes.
  
  
  METHODS
  PubMed and reference lists of recent reviews.
  
  
  METHODS
  We evaluated tests for: (a) single gene products; (b) genetic variations affecting risk of ovarian cancer; (c) gene expression; and (d) proteomics. For tests covered in recent evidence reports (cancer antigen 125 [CA-125] and breast cancer genes 1 and 2 [BRCA1/2]), we added studies published subsequent to the reports. We sought evidence on: (a) the analytic performance of tests in clinical laboratories; (b) the sensitivity and specificity of tests in different patient populations; (c) the clinical impact of testing in asymptomatic women, women with suspected ovarian cancer, and women with diagnosed ovarian cancer; (d) the harms of genomic testing; and (e) the impact of direct-to-consumer and direct-to-physician advertising on appropriate use of tests. We also constructed a computer simulation model to test the impact of different assumptions about ovarian cancer natural history on the relative effectiveness of different strategies.
  
  
  RESULTS
  There are reasonable data on the clinical laboratory performance of most radioimmunoassays, but the majority of the data on other genomic tests comes from research laboratories. Genomic test sensitivity/specificity estimates are limited by small sample sizes, spectrum bias, and unrealistically large prevalences of ovarian cancer; in particular, estimates of positive predictive values derived from most of the studies are substantially higher than would be expected in most screening or diagnostic settings. We found no evidence relevant to the question of the impact of genomic tests on health outcomes in asymptomatic women. Although there is a relatively large literature on the association of test results and various clinical outcomes, the clinical utility of changing management based on these results has not been evaluated. We found no evidence that genomic tests for ovarian cancer have unique harms beyond those common to other tests for genetic susceptibility or other tests used in screening, diagnosis, and management of ovarian cancer. Studies of a direct-to-consumer campaign for BRCA1/2 testing suggest increased utilization, but the effect on "appropriateness" was unclear. Model simulations suggest that annual screening, even with a highly sensitive test, will not reduce ovarian cancer mortality by more than 50 percent; frequent screening has a very low positive predictive value, even with a highly specific test.
  
  
  CONCLUSIONS
  Although research remains promising, adaptation of genomic tests into clinical practice must await appropriately designed and powered studies in relevant clinical settings.
authors.forename: Evan R
authors.initials: ER
authors.lastname: Myers
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Havrilesky
authors.forename: Shalini L
authors.initials: SL
authors.lastname: Kulasingam
authors.forename: Gillian D
authors.initials: GD
authors.lastname: Sanders
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Cline
authors.forename: Rebecca N
authors.initials: RN
authors.lastname: Gray
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
authors.forename: Douglas C
authors.initials: DC
authors.lastname: McCrory
mesh_terms: D000367:Age Factors; D018394:CA-125 Antigen / Q000097:blood; D005260:Female; D020869:Gene Expression Profiling; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing; D006801:Humans; D040541:Marketing; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control / Q000628:therapy; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D018394:CA-125 Antigen