title: Variants of uncertain significance in BRCA testing: evaluation of surgical decisions, risk perception, and cancer distress.
abstract: Studies suggest that patients carrying a BRCA variant of uncertain significance (VUS) may have lingering confusion concerning results interpretation. Counseling for uninformative BRCA-negative (UN) results is thought to be more straightforward, despite the fact that both results lead to similar methods of empiric cancer risk counseling. This study compared surgical choices and perceptions between 71 patients with VUS results and 714 patients with UN results. All patients underwent genetic counseling because of a personal or family history of breast or ovarian cancer between 1997 and 2010, and completed a 2-year follow-up survey. Risk-reducing mastectomy rates in both groups were 7% (p = 1.00) and risk-reducing oophorectomy rates were 5% and 3%, respectively (p = 0.42). The VUS group reported less cancer distress reduction than the UN group (23.0% vs 35.8%, respectively, p = 0.043). Over 90% of both groups found the counseling process helpful. Overall, the study suggests that VUS results disclosed in genetic counseling did not cause excessive surgery or exaggerated cancer distress, though patients with a VUS found counseling somewhat less informative or reassuring. Future research on communication of VUS results, including pre-and post-test counseling, is essential for full realization of the potential for genomic medicine.
authors: Division of Clinical Cancer Genetics, City of Hope, Duarte, CA, USA.
authors: J O
authors: JO
authors: Culver
authors: C D
authors: CD
authors: Brinkerhoff
authors: J
authors: J
authors: Clague
authors: K
authors: K
authors: Yang
authors: K E
authors: KE
authors: Singh
authors: S R
authors: SR
authors: Sand
authors: J N
authors: JN
authors: Weitzel
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000523:psychology*; D005260:Female; D005500:Follow-Up Studies; D005817:Genetic Counseling / Q000523:psychology; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008408:Mastectomy / Q000523:psychology / Q000706:statistics & numerical data; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000523:psychology*; D010052:Ovariectomy / Q000523:psychology / Q000706:statistics & numerical data; D018570:Risk Assessment; D013315:Stress, Psychological; D035501:Uncertainty
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: BRCA1 gene; BRCA2 gene; genetic counseling; hereditary breast and ovarian cancer syndrome; mutation missense; variant of uncertain significance