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


CONCLUSIONS
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.
Department of Gynecologic Oncology, Kaiser Permanente San Francisco Medical Center, San Francisco, California, USA.
Christine
C
Garcia
Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
Liisa
L
Lyon
Department of Gynecologic Oncology, Kaiser Permanente San Francisco Medical Center, San Francisco, California, USA.
Ramey D
RD
Littell
Department of Gynecologic Oncology, Kaiser Permanente San Francisco Medical Center, San Francisco, California, USA.
C Bethan
CB
Powell
D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D002140:California; D005260:Female; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D015438:Health Behavior; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010052:Ovariectomy; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012308:Risk Management / Q000379:methods*; D016896:Treatment Outcome
D019313:BRCA1 Protein; C492913:BRCA1 protein, human