title: Variants of unknown significance in BRCA testing: impact on risk perception, worry, prevention and counseling.
abstract: BACKGROUND
  Sequence-based BRCA testing can identify variants of unknown significance (VUS). Relatively little is known about how well a test outcome of VUS is understood by patients and referring physicians, and whether genetic counselors have an interest in the development of VUS management guidelines.
  
  
  METHODS
  Self-administered questionnaires were completed by 36 VUS counselees, 75 women with a BRCA mutation and 33 with no mutation found (NMF). We also surveyed 24 genetic counselors and 22 referring family physicians.
  
  
  RESULTS
  One-third of VUS failed to recall the clinical significance of their result. Incorrect recall was significantly higher among VUS with high-school-only education (70% versus 19%, P = 0.02). Risk perception, cancer worry and uptake of surveillance and risk-reducing surgeries among VUS counselees were more similar to NMF than to mutation carriers. Genetic counselors accurately predicted the difficulties counselees would have with a VUS result and identified the need for VUS management guidelines. Referring physicians unanimously stated that genetic testing was indicated for unaffected siblings of VUS carriers.
  
  
  CONCLUSIONS
  While VUS seems to be correctly perceived by counselees as more similar to NMF than to a pathogenic mutation, miscomprehension of VUS is more common, particularly in counselees with lower education. VUS-related educational interventions for both VUS counselees and their referring physicians are needed. We encourage the development of national VUS-related guidelines for genetic counselors.
authors.affiliation: Department of Medicine, Division of Oncology, St Michael's Hospital, Toronto.
authors.forename: S
authors.initials: S
authors.lastname: Richter
authors.forename: I
authors.initials: I
authors.lastname: Haroun
authors.forename: T C
authors.initials: TC
authors.lastname: Graham
authors.forename: A
authors.initials: A
authors.lastname: Eisen
authors.forename: A
authors.initials: A
authors.lastname: Kiss
authors.forename: E
authors.initials: E
authors.lastname: Warner
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D017422:Sequence Analysis, DNA; D011795:Surveys and Questionnaires
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: BRCA1; BRCA2; breast cancer; variants; variants of unknown significance