Benefits and costs of screening Ashkenazi Jewish women for BRCA1 and BRCA2

Purpose: To determine the survival benefit and cost-effectiveness of screen ing Ashkenazi Jewish women for three specific BRCA1/2 gene mutations. Methods: We used a Markov model and Monte Carlo analysis to estimate the su rvival benefit and cost-effectiveness of screening for three specific mutat ions in a population in which their prevalence is 2.5% and the associated c ancer risks are 56% for breast cancer and 16% for ovarian cancer. We assume d that the sensitivity and specificity of the test were 98% and 99%, respec tively, that bilateral prophylactic oophorectomy would reduce ovarian cance r risk by 45%, and that bilateral prophylactic mastectomy would reduce brea st cancer risk by 90%. We used Medicare payment data for treatment costs an d Surveillance, Epidemiology, and End Results data for cancer survival. Results: Our model suggests that genetic screening of this population could prolong average nondiscounted survival by 38 days (95% probability interva l, 22 to 57 days) for combined surgery, 33 days (95% probability interval, 18 to 43 days) for mastectomy, Il days (95% probability interval, 4 to 25 d ays) for oophorectomy, and 6 days (95% probability interval, 3 to 8 days) f or surveillance, The respective cost-effectiveness ratios per life-year sav ed, with a discount rate of 3%, are $20,717, $29,970, $72,780, and $134,273 . Conclusion: In this Ashkenazi Jewish population, with a high prevalence of BRCA1/2 mutations, genetic screening may significantly increase average sur vival and, depending on costs and screening/treatment strategies, may be co st-effective by the standards of accepted cancer screening tests. According to our model, screening is cost-effective only if all women who test posit ive undergo prophylactic surgery. These estimates require confirmation thro ugh prospective observational studies and clinical trials. (C) 1999 by Amer ican Society of Clinical Oncology.