Comparison of risk management strategies between women testing positive for a BRCA variant of unknown significance and women with known BRCA deleterious mutations.

Purpose: The aim of this article is to describe cancer risk-reducing behaviors of women with BRCA variants of unknown significance.

Methods: A retrospective chart review from 1995 to 2012 identified women with BRCA mutations in a northern California community system. Exclusion criteria included loss of membership/death within 1 year of testing, prior ovarian cancer, or bilateral salpingo-oophorectomy. Primary outcomes were rate of risk-reducing mastectomy and risk-reducing salpingo-oophorectomy.

Results: The mean age of the 69 variant of unknown significance carriers was 50 vs. 47 years for the 305 women with a deleterious mutation. Women with a variant of unknown significance were followed for a median of 69 months. Among women with a variant of unknown significance, 30% underwent risk-reducing salpingo-oophorectomy and 11% underwent risk-reducing mastectomy, as compared with 74 and 44%, respectively, for women with a deleterious mutation. Women with a deleterious mutation were more likely to undergo surveillance in the first year after testing. The odds ratios are as follows: 2.1 for mammogram, 6.0 for magnetic resonance imaging, 7.7 for Ca-125, and 5.0 for transvaginal ultrasound. Fifty-six percent of women with a variant of unknown significance were reclassified after a median of 39 months, longer than the median time to risk-reducing salpingo-oophorectomy (18.6 months) or risk-reducing mastectomy (20.1 months).

Conclusion: Uptake of risk-reducing strategies among women with a variant of unknown significance is lower than among women with a deleterious mutation. Given the prognostic uncertainty and high rate of reclassification for women with a variant of unknown significance, individualizing counseling and directing efforts toward surveillance, chemoprevention, or salpingectomy are recommended.