RELATIONSHIP OF SERUM DEHYDROEPIANDROSTERONE (DHEA), DHEA SULFATE, AND 5-ANDROSTENE-3-BETA,17-BETA-DIOL TO RISK OF BREAST-CANCER IN POSTMENOPAUSAL WOMEN

Laboratory evidence suggests a role for dehydroepiandrosterone (DHEA) and its metabolite 5-androstene-3 beta,17 beta-diol (ADIOL) in mammary tumor growth. Serum DHEA also has been related to breast cancer in po stmenopausal women, but the relationship of ADIOL to risk has not been evaluated previously. To assess the relationship of serum DHEA, its s ulfate (DHEAS), and ADIOL with breast cancer risk in postmenopausal wo men, we conducted a prospective nested case-control study using serum from the Columbia, MO Breast Cancer Serum Bank. Cases included 71 heal thy postmenopausal volunteers not taking replacement estrogens when th ey donated blood and who were diagnosed with breast cancer up to 10 ye ars later (median, 2.9 years). Two randomly selected controls, who als o were postmenopausal and not taking estrogens, were matched to each c ase on exact age, date (+/-1 year), and time (+/-2 h) of blood collect ion. Significant (trend P = 0.02) gradients of increasing risk of brea st cancer were observed for increasing concentrations of DHEA and ADIO L, and women whose serum levels of these hormones were in the highest quartiles were at a significantly elevated risk compared to those in t he lowest; their risk ratios were 4.0 (95% confidence interval (CI), 1 .3-11.8) and 3.0 (95% CI, 1.0-8.6), respectively. The relationship of DHEAS to breast cancer was less consistent, but women whose serum DHEA S concentration was in the highest quartile also exhibited a significa ntly elevated risk ratio of 2.8 (95% CI, 1.1-7.4). Results of this pro spective study support a role for the adrenal androgens, DHEA, DHEAS, and ADIOL, in the etiology of breast cancer.