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Sources of Elevated Serum Androgens in Postmenopausal Women Who Develop Breast Cancer

Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 [J. F. D.]; Laboratoire de Biologie Hormonale, Centre Hospitalier Universitaire Saint-Louis,75010 Paris, France [P. B.]; Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, California 90033 [F. Z. S.]; Departments of Obstetrics and Gynecology and Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655 [C. L.]; Salomon Smith Barney, New York, New York 10013 [A. A. T.]; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892 [R. T. F.]; Information Management Services Incorporated, Silver Spring, Maryland 20904 [N. S.]; and Department of Surgery, University of Missouri Health Sciences Center, Columbia, Missouri 65212 [H. E. S.]

Postmenopausal women with elevated serum androgens are at an increased risk of breast cancer. High dehydroepiandrosterone sulfate concentrations in these women suggest increased adrenal secretion. Both the adrenals and ovaries could contribute to elevated concentrations of androstenedione (⁴A). 11ß-Hydroxyandrostenedione (11ßOHA) is elevated, and the ⁴A:11ßOHA ratio is depressed when the adrenals are the primary source of elevated ⁴A in women. Conversely, ⁴A:11ßOHA is elevated when the ovaries are the primary source. We prospectively evaluated associations of serum 11ßOHA and ⁴A:11ßOHA with breast cancer in the Columbia, Missouri Serum Bank to identify the source of elevated ⁴A related to risk. Fifty-three postmenopausal women who were not taking estrogens when they donated blood and were diagnosed with breast cancer up to 10 years later (median, 2.9 years) served as cases. Two controls, who were also postmenopausal and not taking estrogens, were matched to each case on age, date, and time of blood collection. Serum ⁴A concentration was significantly (trend P = 0.02) positively associated with breast cancer risk. Adjusted risk ratios for women in the lowest to highest tertiles were 1.0, 1.6, and 2.4 [95% confidence interval (CI), 0.9–6.5]. However, neither 11ßOHA concentration nor ⁴A:11ßOHA was related to risk. Comparable risk ratios were 1.0, 1.2, and 1.4 (95% CI, 0.5–3.6) for 11ßOHA and 1.0, 1.2, and 1.2 (95% CI, 0.4–3.5) for ⁴A:11ßOHA. Our results suggest that neither the ovaries nor adrenals are the predominant source of elevated serum ⁴A in postmenopausal women who develop breast cancer, but rather both may contribute.