The influence of BRCA variants of unknown significance on cancer risk management decision-making

• Published in: Journal of gynecologic oncology Vol. 30; no. 4; pp. 1 - 10
• Main Authors: Jing-yi Chern, Sarah S. Lee, Melissa K. Frey, Jessica Lee, Stephanie V. Blank
• Format: Journal Article
• Language: Korean
• Published: 대한부인종양학회 01-07-2019
• Subjects: Genetic Testing; Hereditary Breast and Ovarian Cancer Syndrome; Risk Assessment; Salpingo-oophorectomy
• ISSN: 2005-0380

Objective: To compare gynecological cancer risk management between women with BRCA variants of unknown significance (VUS) to women with negative genetic testing.
Methods: Ninety-nine patients whose BRCA genetic testing yielded VUS were matched with 99 control patients with definitive negative BRCA results at a single institution. Demographics and risk management decisions were obtained through chart review. Primary outcome was the rate of risk-reducing bilateral salpingo-oophorectomy (RRBSO). Chi square tests, t-tests, and logistic regression were performed, with significance of p<0.05.
Results: VUS patients were more likely to be non-Caucasian (p=0.000) and of Ashkenazi-Jewish descent (p=0.000). There was no difference in gynecologic oncology referrals or recommendations to screen or undergo risk-reducing surgery for VUS vs. negative patients. Ultimately, 44 patients (22%) underwent RRBSO, with no significant difference in surgical rate based on the presence of VUS. Ashkenazi-Jewish descent was associated with a 4.5 times increased risk of RRBSO (OR=4.489; 95% CI=1.484-13.579) and family history of ovarian cancer was associated with a 2.6 times risk of RRBSO (OR=2.641; 95% CI=1.107-6.299).
Conclusion: In our institution, patients with VUS were surgically managed similarly to those with negative BRCA testing. The numbers of patients with VUS are likely to increase with the implementation of multi-gene panel testing. Our findings underscore the importance of genetic counseling and individualized screening and prevention strategies in the management of genetic testing results.