J Gynecol Oncol.  2019 Jul;30(4):e60. 10.3802/jgo.2019.30.e60.

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

• Chern JY
• Lee SS
• Frey MK
• Lee J
• Blank SV

• KMID: 2450239
• DOI: http://doi.org/10.3802/jgo.2019.30.e60

Abstract

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.

Keyword

Genetic Testing; Hereditary Breast and Ovarian Cancer Syndrome; Salpingo-oophorectomy; Risk Assessment

MeSH Terms

Demography
Female
Genetic Counseling
Genetic Testing
Hereditary Breast and Ovarian Cancer Syndrome
Humans
Logistic Models
Mass Screening
Ovarian Neoplasms
Referral and Consultation
Risk Assessment
Risk Management*