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The Association of Plasma DHEA and DHEA Sulfate with Breast Cancer Risk in Predominantly Premenopausal Women

¹ Channing Laboratory, Department of Medicine and ² Department of Obstetrics, Gynecology, and Reproductive Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of ³ Epidemiology and ⁴ Biostatistics, Harvard School of Public Health, Boston, Massachusetts; and ⁵ Academic Department of Biochemistry, Royal Marsden Hospital, London, United Kingdom

Requests for reprints: Shelley S. Tworoger, Channing Laboratory, 181 Longwood Avenue, 3rd Floor, Boston, MA 02115. Phone: 617-525-2087; Fax: 617-525-2008. E-mail: nhsst{at}channing.harvard.edu

Concentrations of adrenal androgens are positively associated with postmenopausal breast cancer risk; however, results in premenopausal women are conflicting. Therefore, we conducted a prospective nested case-control study within the Nurses' Health Study II cohort to examine the relationship of DHEA and DHEA sulfate (DHEAS) with breast cancer risk in predominantly premenopausal women. Blood samples were collected from 1996 to 1999. The analysis included 317 cases of breast cancer diagnosed after blood collection and before June 1, 2003; for each case, two controls were matched on age, fasting status, time of day and month of blood collection, race/ethnicity, and timing of blood draw within the menstrual cycle. No associations were observed between DHEA or DHEAS levels and breast cancer risk overall [in situ and invasive; DHEA relative risk (RR), top versus bottom quartile, 1.2; 95% confidence interval (95% CI), 0.8-1.8, P_trend = 0.53; DHEAS RR, 1.3; 95% CI, 0.9-2.0; P_trend = 0.07]. However, both DHEA and DHEAS were positively associated with estrogen receptor–positive/progesterone receptor–positive breast cancer (DHEA RR, 1.6; 95% CI, 0.9-2.8, P_trend = 0.09; DHEAS RR, 1.9; 95% CI, 1.1-3.3, P_trend = 0.02). We observed a significant interaction by age, with an RR for DHEAS of 0.8 (95% CI, 0.4-1.5, P_trend = 0.62) for women <45 years old and 2.0 (95% CI, 1.2-3.5, P_trend = 0.003) for women 45 years old; results were similar for DHEA. Our results suggest that adrenal androgens are positively associated with breast cancer among predominately premenopausal women, especially for estrogen receptor–positive/progesterone receptor–positive tumors and among women over age 45 years. (Cancer Epidemiol Biomarkers Prev 2006;15(5):967–71)

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