title: Understanding of BRCA VUS genetic results by breast cancer specialists.
abstract: BACKGROUND
  Mainstreaming genetic medicine, increased media coverage and clinical trials for BRCA mutation carriers are leading oncologists into more patient discussions about BRCA genetic testing. BRCA variants of uncertain significance (VUS) occur in 10-20% of tests. VUS detection introduces additional uncertainty for patient and potentially clinician. We aimed to explore the ability of breast cancer specialists (BCS) in the UK to correctly respond to a VUS report.
  
  
  METHODS
  A survey sent to 800 UK BCS collected demographics data, VUS general knowledge and interpretation and communication based on two genetics reports. A separate survey of UK clinical geneticists collected demographics data, laboratory reporting practice and methods used to clarify VUS pathogenicity including classification systems.
  
  
  RESULTS
  Of the 155 BCS (22.5%) who completed the survey, 12% reported no genetics training. Ninety five percent referred patients for BRCA genetic tests, 71% felt unsure about the clinical implications of the test reports presented here. A VUS report from a patient with a positive family history was interpreted and theoretically communicated correctly by 94% but when presented with a different VUS report with no management guidance and negative family history, 39% did not know how to communicate this result to the patient. Geneticists reported multiple VUS classification systems; the most commonly used was word-based in 32%.
  
  
  CONCLUSIONS
  A consistent and standardised format to report particularly VUS results across all diagnostic laboratories plus additional training of UK BCS will be necessary for effective mainstreaming of BRCA testing to the oncology clinic.
authors.affiliation: Cancer Sciences Academic Unit and University of Southampton Clinical Trials Unit, Faculty of Medicine, University of Southampton and University Hospital Southampton Foundation Trust, Tremona Road, Southampton, SO16 6YD, UK. bryony_eccles@hotmail.com.
authors.forename: B K
authors.initials: BK
authors.lastname: Eccles
authors.affiliation: Cancer Sciences Academic Unit and University of Southampton Clinical Trials Unit, Faculty of Medicine, University of Southampton and University Hospital Southampton Foundation Trust, Tremona Road, Southampton, SO16 6YD, UK. E.Copson@soton.ac.uk.
authors.forename: E
authors.initials: E
authors.lastname: Copson
authors.affiliation: Cancer Sciences Academic Unit and University of Southampton Clinical Trials Unit, Faculty of Medicine, University of Southampton and University Hospital Southampton Foundation Trust, Tremona Road, Southampton, SO16 6YD, UK. t.maishman@soton.ac.uk.
authors.forename: T
authors.initials: T
authors.lastname: Maishman
authors.affiliation: Cambridge Breast Unit and NIHR Cambridge Biomedical Research Centre, University of Cambridge NHS Foundation Hospitals, Hills Road, Cambridge, UK. ja344@medschl.cam.ac.uk.
authors.forename: J E
authors.initials: JE
authors.lastname: Abraham
authors.affiliation: Cancer Sciences Academic Unit and University of Southampton Clinical Trials Unit, Faculty of Medicine, University of Southampton and University Hospital Southampton Foundation Trust, Tremona Road, Southampton, SO16 6YD, UK. d.m.eccles@soton.ac.uk.
authors.forename: D M
authors.initials: DM
authors.lastname: Eccles
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D014644:Genetic Variation; D007722:Health Knowledge, Attitudes, Practice; D006801:Humans; D008875:Middle Aged; D010820:Physicians; D006113:United Kingdom
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human