Originally published as JCO Early Release 10.1200/JCO.2005.03.7432 on March 27 2006

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Endogenous Steroid Hormone Concentrations and Risk of Breast Cancer: Does the Association Vary by a Woman's Predicted Breast Cancer Risk?

A. Heather Eliassen, Stacey A. Missmer, Shelley S. Tworoger, Susan E. Hankinson

From the Channing Laboratory, Department of Medicine and the Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School; Department of Epidemiology, Harvard School of Public Health, Boston, MA

Address reprint requests to Heather Eliassen, ScD, Channing Laboratory, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115; e-mail: heather.eliassen{at}channing.harvard.edu

PURPOSE: To examine whether the associations of endogenous estrogens and testosterone with breast cancer risk differ between high- and low-risk women, as determined by the Gail model and the Rosner and Colditz model, and by family history of breast cancer.

METHODS: We conducted a prospective nested case-control study within the Nurses' Health Study. From 1989 or 1990 until June 2000, blood samples were collected, 418 breast cancer patient cases were identified, and two controls (total n = 817) were matched to each case. We classified women as high or low risk based on their family history of breast cancer, their 5-year Gail risk score, and their 5-year Rosner and Colditz risk score. Multivariate relative risks (RR) and 95% CI were calculated by unconditional logistic regression, adjusting for matching and breast cancer risk factors.

RESULTS: Estrone sulfate was statistically significantly associated with breast cancer risk among women with low (< 1.66%) and high ( 2.52%; 75th percentile) Gail predicted risk (fourth v first quartile RR = 3.6; 95% CI, 1.9 to 7.0; RR = 2.5; 95% CI, 1.2 to 5.1, respectively). Testosterone results were similar across strata of predicted risk, with two times the risk in the fourth (v first) quartile. Estradiol appeared more strongly associated with breast cancer in women with higher predicted risk (RR = 4.5; 95% CI, 2.1 to 9.5) compared with women with lower risk (RR = 2.1; 95% CI, 1.2 to 3.6), but differences were not statistically significant. Results were similar across predicted Rosner and Colditz risk scores.

CONCLUSION: These data suggest that higher levels of endogenous estrogens and testosterone are associated with increased breast cancer risk, regardless of predicted risk or family history of breast cancer.

Supported by Research Grants No. CA49449 and CA87969 from the National Cancer Institute, Cancer Education and Career Development Grant No. R25 CA098566-02 from the National Cancer Institute (A.H.E.), and in part by Training Grant in Cancer Epidemiology No. T32 CA090001-281 from the National Cancer Institute (S.A.M. and S.S.T.).

Presented in part at the American Association for Cancer Research 96th Annual Meeting, Anaheim, CA, April 16-20, 2005 (poster session).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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