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

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 (Δ4A). 11β-Hydroxyandrostenedione (11βOHA) is elevated, and the Δ4A:11βOHA ratio is depressed when the adrenals are the primary source of elevated Δ4A in women. Conversely, Δ4A:11βOHA is elevated when the ovaries are the primary source. We prospectively evaluated associations of serum 11βOHA and Δ4A:11βOHA with breast cancer in the Columbia, Missouri Serum Bank to identify the source of elevated Δ4A 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 Δ4A 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 11βOHA concentration nor Δ4A:11βOHA was related to risk. Comparable risk ratios were 1.0, 1.2, and 1.4 (95% CI, 0.5–3.6) for 11βOHA and 1.0, 1.2, and 1.2 (95% CI, 0.4–3.5) for Δ4A:11βOHA. Our results suggest that neither the ovaries nor adrenals are the predominant source of elevated serum Δ4A in postmenopausal women who develop breast cancer, but rather both may contribute.