Follow-up of carriers of BRCA1 and BRCA2 variants of unknown significance: variant reclassification and surgical decisions

Genet Med. 2011 Dec;13(12):998-1005. doi: 10.1097/GIM.0b013e318226fc15.

Abstract

Purpose: : 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.

Conclusion: : 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / surgery
  • Female
  • Follow-Up Studies
  • Genetic Counseling
  • Genetic Testing / standards*
  • Heterozygote
  • Humans
  • Mastectomy
  • Middle Aged
  • Mutation
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / surgery
  • Ovariectomy
  • Prospective Studies
  • Risk
  • Risk Reduction Behavior
  • Uncertainty

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Biomarkers, Tumor