title: Estimated risk of radiation-induced breast cancer from mammographic screening for young BRCA mutation carriers.
abstract: 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.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. aberring@jhsph.edu
authors.forename: Amy
authors.initials: A
authors.lastname: Berrington de Gonzalez
authors.forename: Christine D
authors.initials: CD
authors.lastname: Berg
authors.forename: Kala
authors.initials: K
authors.lastname: Visvanathan
authors.forename: Mark
authors.initials: M
authors.lastname: Robson
mesh_terms: D000328:Adult; D000367:Age Factors; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006579:Heterozygote; D006801:Humans; D008327:Mammography / Q000009:adverse effects*; D008403:Mass Screening / Q000009:adverse effects* / Q000379:methods; D015233:Models, Statistical; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology* / Q000209:etiology; D018570:Risk Assessment; D012307:Risk Factors