Journal of the National Cancer Institute Advance Access published online on January 27, 2009
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djn440
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© The Author 2009. Published by Oxford University Press.
BRIEF COMMUNICATION |
Estimated Risk of Radiation-Induced Breast Cancer From Mammographic Screening for Young BRCA Mutation Carriers
Affiliations of authors: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (ABdG, KV); Early Detection Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD (CDB); Clinical Genetics and Breast Cancer Medicine Services, Memorial Sloan-Kettering Cancer Center, New York, NY (MR)
Correspondence to: Amy Berrington de Gonzalez, DPhil, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205 (e-mail: aberring{at}jhsph.edu).
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.
| CONTEXT AND CAVEATS Prior knowledge Women with BRCA mutations are encouraged to start mammographic screening at age 25–30 years because of their higher risk of breast cancer. Among average-risk women, mammography reduces breast cancer mortality by 15%–25% (approximately one in 1000 or less). Study design A model to estimate the lifetime risk of death from radiation-induced breast cancer from five annual mammograms among young BRCA mutation carriers age 40 years and younger was developed and the estimates were used to determine in what age group screening would be beneficial to these women, assuming a 25% or less reduction in mortality from mammography. Contribution The risk of radiation-induced breast cancer deaths decreased with increasing age at screening, such that screening at age 35–39 years would have a net benefit. Implications Based on this model, the reduction in breast cancer mortality from screening among women with BRCA mutations is not substantially greater than the risk of radiation-induced breast cancer mortality when screening before age 34 years. Limitations It is unknown how much mammography reduces breast cancer mortality in this population (ie, whether it is by 25% or less). From the Editors
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Manuscript received May 12, 2008; revised October 23, 2008; accepted October 28, 2008.
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J Natl Cancer Inst 2009 101: 127.
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