PURPOSE: Women who carry a BRCA1/2 mutation can reduce their risk of breast and ovarian cancer if they undergo bilateral prophylactic mastectomies and oophorectomies. However, women's willingness to undergo these surgeries and the impact of these surgeries on a woman's quality of life varies tremendously. We sought to evaluate how women's preferences for prophylactic surgeries impact the health and economic effects of screening for BRCA1/2 mutations.

METHODS: We used a Markov model to evaluate the cost-effectiveness of genetic screening on women from four populations: the general population; the Ashkenazi Jewish population; a “high-risk” general population (women with a first degree relative with either ovarian cancer or breast cancer before age 35); and a “high-risk” Ashkenazi Jewish population (women with a first degree relative with either ovarian cancer or breast cancer before age 40). Transition probabilities, test characteristics, and costs were estimated from the literature.

RESULTS: Screening for BRCA1/2 mutations in the general population is prohibitively expensive regardless of a woman's preference for prophylactic surgery. Screening women from the Ashkenazi Jewish or “high-risk” general populations (BRCA1/2 prevalence =2.5 to 4%) has an incremental cost-effectiveness ratio (ICER) <$100,000/QALY if the woman's preferences for both surgeries are high and if BRCA1+ women undergo prophylactic oophorectomies and BRCA2+ women undergo prophylactic mastectomy. If a woman's preference for one surgery is high and the other surgery low then screening for BRCA1/2 has an ICER <$100,000/QALY if women who test positive for either mutation undergo the preferred prophylactic surgery. If preferences for both prophylactic surgeries are low screening is prohibitively expensive. Screening “high-risk” Ashkenazi Jewish women (BRCA1/2 prevalence =10%) has an ICER <$100,000/QALY if preferences for both surgeries are high and BRCA1+ women undergo both prophylactic surgeries and BRCA2+ women undergo prophylactic oophorectomies. If preference for one surgery is high and for the other surgery low the results are similar to the average-risk Ashkenazi Jewish population. If preferences for both surgeries are low, screening still has an ICER <$100,000/QALY if women who test BRCA1/2+ undergo intensive surveillance.

CONCLUSIONS: The benefits and cost-effectiveness of screening for BRCA1/2 mutations varies greatly depending on a woman's utilities for prophylactic surgeries. Current guidelines recommend screening primarily based on the prior probability of BRCA mutations and should be revised to reflect the importance of women's utilities.