Journal of the National Cancer Institute Advance Access originally published online on March 10, 2009
JNCI Journal of the National Cancer Institute 2009 101(6):384-398; doi:10.1093/jnci/djp018
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© The Author 2009. Published by Oxford University Press.
ARTICLES |
Prevention of Breast Cancer in Postmenopausal Women: Approaches to Estimating and Reducing Risk
Affiliations of authors: San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA (SRC, WSB); Department of Medicine (JAT, EZ, KK), Department of Epidemiology and Biostatistics (SRC, SB, KK), and Department of Radiology (JS, RS-B), University of California, San Francisco, CA; University of California, Los Angeles, CA (SB); Cancer Research UK, London, UK (JC); Magee Women’s Cancer Center, University of Pittsburgh, Pittsburgh, PA (VV); Mayo Clinic College of Medicine, Rochester, MN (CV)
Correspondence to: Steven R. Cummings, MD, S.F. Coordinating Center, 185 Berry St, Ste 5700, San Francisco, CA 94107 (e-mail: scummings{at}sfcc-cpmc.net).
Background: It is uncertain whether evidence supports routinely estimating a postmenopausal woman's risk of breast cancer and intervening to reduce risk.
Methods: We systematically reviewed prospective studies about models and sex hormone levels to assess breast cancer risk and used meta-analysis with random effects models to summarize the predictive accuracy of breast density. We also reviewed prospective studies of the effects of exercise, weight management, healthy diet, moderate alcohol consumption, and fruit and vegetable intake on breast cancer risk, and used random effects models for a meta-analyses of tamoxifen and raloxifene for primary prevention of breast cancer. All studies reviewed were published before June 2008, and all statistical tests were two-sided.
Results: Risk models that are based on demographic characteristics and medical history had modest discriminatory accuracy for estimating breast cancer risk (c-statistics range = 0.58–0.63). Breast density was strongly associated with breast cancer (relative risk [RR] = 4.03, 95% confidence interval [CI] = 3.10 to 5.26, for Breast Imaging Reporting and Data System category IV vs category I; RR = 4.20, 95% CI = 3.61 to 4.89, for >75% vs <5% of dense area), and adding breast density to models improved discriminatory accuracy (c-statistics range = 0.63–0.66). Estradiol was also associated with breast cancer (RR range = 2.0–2.9, comparing the highest vs lowest quintile of estradiol, P < .01). Most studies found that exercise, weight reduction, low-fat diet, and reduced alcohol intake were associated with a decreased risk of breast cancer. Tamoxifen and raloxifene reduced the risk of estrogen receptor–positive invasive breast cancer and invasive breast cancer overall.
Conclusions: Evidence from this study supports screening for breast cancer risk in all postmenopausal women by use of risk factors and breast density and considering chemoprevention for those found to be at high risk. Several lifestyle changes with the potential to prevent breast cancer should be recommended regardless of risk.
| CONTEXT AND CAVEATS Prior knowledge Whether evidence supports routinely estimating a postmenopausal woman's risk of breast cancer and intervening to reduce risk is not clear. Study design A combination of systematic review and meta-analysis was used to analyze published data from prospective studies on risk assessment models and breast cancer risk and sex hormone levels, breast density, exercise, weight management, diet, tamoxifen, and raloxifene. Contribution Results of this analysis support screening for breast cancer risk in all postmenopausal women by use of risk factors and breast density, considering chemoprevention for women found to be at high risk, and encouraging lifestyle changes that may decrease the risk of breast cancer regardless of risk. Implications Systems need to be developed to assess and report the results of various tests, including risk factor analyses, breast density, and appropriate referral for genetic counseling, to name just a few. Limitations The studies reviewed had diverse designs, diverse populations with different degrees of risk, and diverse methods of analyzing and expressing data, which precluded reporting the results about benefits and harms as absolute rates. Studies on lifestyle changes to reduce risk are generally observational and rely on recall. From the Editors
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Manuscript received March 21, 2008; revised December 12, 2008;
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