Journal of the National Cancer Institute Advance Access originally published online on July 24, 2007
JNCI Journal of the National Cancer Institute 2007 99(15):1178-1187; doi:10.1093/jnci/djm062
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© The Author 2007. Published by Oxford University Press.
ARTICLES |
Endogenous Hormone Levels, Mammographic Density, and Subsequent Risk of Breast Cancer in Postmenopausal Women
Affiliations of authors: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (RMT, SEH); Department of Epidemiology, Harvard School of Public Health, Boston, MA (RMT, GAC, SEH); Cancer Genetics and Epidemiology Program, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC (CB); Department of Surgery, Washington University School of Medicine, St. Louis, MO (GAC)
Correspondence to: Rulla M. Tamimi, ScD, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA 02115 (e-mail: rulla.tamimi{at}channing.harvard.edu).
Background: Mammographic density and circulating sex hormones are two well-confirmed predictors of breast cancer risk. Whether mammographic density reflects levels of endogenous sex hormones is unclear. We examined whether these predictors are independently associated with breast cancer risk in a prospective study.
Methods: We conducted a nested case–control study within the Nurses’ Health Study cohort of 253 case subjects with breast cancer and 520 control subjects. All participants were postmenopausal women who were not using postmenopausal hormones at the time of both blood collection and mammography. Plasma levels of estradiol, free estradiol, testosterone, and free testosterone were evaluated. Mammographic density was assessed by use of computer-assisted analysis of mammograms. Logistic regression models that were adjusted for matching variables and potential confounders were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided.
Results: Levels of circulating sex steroids and mammographic density were both statistically significantly and independently associated with breast cancer risk. The relative risk of breast cancer associated with mammographic density (RR for highest quartile compared with lowest quartile = 3.8, 95% CI = 2.2 to 6.6; Ptrend<.001) changed little when the analysis was adjusted for circulating estradiol (RR = 3.9, 95% CI = 2.2 to 6.9; Ptrend<.001) or circulating testosterone (RR = 4.1, 95% CI = 2.3 to 7.2; Ptrend<.001). Circulating levels of estradiol (RR = 2.4, 95% CI = 1.4 to 4.0) and of testosterone (RR = 2.0, 95% CI = 1.2 to 3.1) were both associated with breast cancer risk, before and after adjustment for mammographic density. In a joint analysis of mammographic density and plasma testosterone, the risk of breast cancer was highest in the highest tertiles of both relative to the lowest tertiles of both (RR = 6.0, 95% CI = 2.6 to 14.0). A similar pattern was observed in the joint analysis of estradiol and mammographic density (RR = 4.1, 95% CI = 1.7 to 9.8).
Conclusions: Circulating sex steroid levels and mammographic density appear strongly and independently associated with the risk of breast cancer in postmenopausal women.
| CONTEXT AND CAVEATS Prior knowledge Mammographic density and circulating sex hormones are two confirmed predictors of breast cancer risk, but it is unclear whether the risk associated with mammographic density is primarily related to levels of endogenous sex hormones. Study design A nested case–control study within the Nurses’ Health Study cohort with 253 case subjects with breast cancer and 520 control subjects who were postmenopausal at the time of blood collection and mammographic examination. Contribution Among postmenopausal women, levels of circulating sex steroids and mammographic density were both statistically significantly and independently associated with breast cancer risk. Implications The mechanism by which mammographic density increases the risk of breast cancer among postmenopausal women is independent of the levels of circulating sex steroid hormones. Limitations Circulating levels of steroid hormones were used as a proxy for the more biologically relevant measure of the levels of steroid hormones in breast tissues.
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Manuscript received December 11, 2006; revised May 22, 2007; accepted June 15, 2007.
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J Natl Cancer Inst 2007 99: 1137.
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