title: Follow-up of carriers of BRCA1 and BRCA2 variants of unknown significance: variant reclassification and surgical decisions.
abstract: OBJECTIVE
  : Approximately 5-10% of patients who undergo genetic testing of BRCA1 and BRCA2 receive a variant of unknown significance (VUS) result. The ambiguous nature of a VUS may increase difficulty in patient understanding and decision making regarding risk reduction and surveillance options, including cancer risk-reducing surgeries. VUS reclassification to benign or deleterious may occur in time; however, clinical decisions may need to be made expeditiously, and some patients may pursue irreversible treatments before VUS reclassification.
  
  
  METHODS
  : We reviewed the surgical decisions of 107 women postdisclosure of a BRCA VUS result counseled at our institute between 1998 and 2009.
  
  
  CONCLUSIONS
  : Among women receiving a BRCA VUS result at our center, 11 of 107 (10.3%) pursued cancer risk-reducing mastectomy and 22 of 107 (20.6%) pursued cancer risk-reducing bilateral salpingo-oophorectomy. Reclassification of VUS occurred up to 9 years after testing, and 5 of 22 (22.7%) women followed up for 8 or more years continue to have a VUS result. We discuss considerations for providers of genetic services to discuss with patients who receive a VUS result.
authors.affiliation: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, USA.
authors.forename: Mitzi L
authors.initials: ML
authors.lastname: Murray
authors.forename: Felecia
authors.initials: F
authors.lastname: Cerrato
authors.forename: Robin L
authors.initials: RL
authors.lastname: Bennett
authors.forename: Gail P
authors.initials: GP
authors.lastname: Jarvik
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D005817:Genetic Counseling; D005820:Genetic Testing / Q000592:standards*; D006579:Heterozygote; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery; D010052:Ovariectomy; D011446:Prospective Studies; D012306:Risk; D040242:Risk Reduction Behavior; D035501:Uncertainty
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor