ABSTRACT: Women who carry BRCA germ line mutations are at high risk for breast and ovarian cancer. The National Comprehensive Cancer Network (NCCN) and other national groups have established guidelines for identification of women at risk for carrying these mutations, referral of these women for genetic testing, and use of risk-reducing strategies for management of those who test positive. Recommended strategies include risk-reducing salpingo-oophorectomy (RRSO) by age of 35 to 40 years; risk-reducing mastectomy (RRM); and surveillance at defined intervals using pelvic ultrasound, CA 125, mammogram, and breast magnetic resonance imaging (MRI). Despite the proven effectiveness of these strategies in reducing risk, their uptake varies greatly.
The aim of this retrospective cohort study was to assess the uptake of these risk management options among women at risk for ovarian and breast cancer who tested positive for BRCA mutations at Kaiser Permanente Northern California, a community-based integrated health system. Management of a cohort of deleterious BRCA mutation carriers (1995–2012) in a community setting was evaluated for consistency with NCCN guidelines. The use of chemoprevention and hormone replacement was also evaluated. Women who tested positive for a mutation were followed at each 12-month interval for 5 years.
Of the 305 eligible women, 170 (56%) were BRCA1 positive, and 135 (44%) were BRCA2 positive. Seventy-four percent of the women testing positive underwent RRSO (only 17% were aged < 40 years), whereas 44% underwent RRM. Median time from testing to both RRSO and RRM was 6 months. The first year after diagnosis, 45% of the women underwent a pelvic ultrasound, dropping to 2.3% by year 5. Similarly in year 1, a total of 47% had at least 1 CA 125, dropping to 2% by year 5. There was a similar drop off from years 1 to 5 among the women undergoing annual MRI and mammogram (from 35% to 3% for MRI and 43% to 7% for mammogram). The frequency of oral contraceptive use was also low (16%); only 1 woman used tamoxifen as chemoprevention for breast cancer.
These findings show that uptake of RRSO in BRCA carriers in a community-based US health system was high, but few were younger than 40 years at the time of surgery. Compliance with NCCN-recommended guidelines for surveillance was low even at 1 year after testing and rapidly declined after the first year. The data show the need for an integrated system for early identification of carriers and improved risk reduction by use of standardized management strategies that improve compliance.