Estimated risk of radiation-induced breast cancer from mammographic screening for young BRCA mutation carriers
BRCA mutation carriers are recommended to start mammographic screening for breast cancer as early as age 25-30 years. We used an excess relative risk model (based on a pooled analysis of three cohorts with 7600 subjects who received radiation exposure) to estimate the lifetime risk of radiation-induced breast cancer from five annual mammographic screenings in young (<40 years) BRCA mutation carriers. We then estimated the reduction in breast cancer mortality required to outweigh the radiation risk. Breast cancer rates for mutation carriers were based on a pooled analysis of 22 pedigree studies with 8139 subjects. For BRCA1 mutation carriers, the estimated lifetime risk of radiation-induced breast cancer mortality per 10,000 women resulting from annual mammography was 26 (95% confidence interval [CI] = 14 to 49) for screening at age 25-29 years, 20 (95% CI = 11 to 39) for screening at age 30-34 years, and 13 (95% CI = 7 to 23) for screening at age 35-39 years. To outweigh these risks, screening would have to reduce breast cancer mortality by 51% (95% CI = 27% to 96%) at age 25-29 years, by 12% (95% CI = 6% to 23%) at age 30-34 years, and by 4% (95% CI = 2% to 7%) at age 35-39 years; estimates were similar for BRCA2 mutation carriers. If we assume that the mortality reduction from mammography is 15%-25% or less for young women, these results suggest that there would be no net benefit from annual mammographic screening of BRCA mutation carriers at age 25-29 years; the net benefit would be zero or small at age 30-34 years, but there should be some net benefit at age 35 or older. These results depend on a number of assumptions due to the absence of empiric data. The impact of varying these assumptions was therefore examined.