RELATION OF SERUM LEVELS OF TESTOSTERONE AND DEHYDROEPIANDROSTERONE-SULFATE TO RISK OF BREAST-CANCER IN POSTMENOPAUSAL WOMEN

The authors examined the relation between postmenopausal serum levels of testosterone and dehydroepiandrosterone sulfate (DHEAS) and subsequ ent risk of breast cancer in a case-control study nested within the Ne w York University Women's Health Study cohort. A specific objective of their analysis was to examine whether androgens had an effect on brea st cancer risk independent of their effect on the biologic availabilit y of estrogen. A total of 130 cases of breast cancer were diagnosed pr ior to 1991 in a cohort of 7,054 postmenopausal women who had donated blood and completed questionnaires at a breast cancer screening clinic in New York City between 1985 and 1991. For each case, two controls w ere selected, matching the case on age at blood donation and length of storage of serum specimens. Biochemical analyses were performed on se ra that had been stored at -80 degrees C since sampling. The present r eport includes a subset of 85 matched sets, for whom at least 6 months had elapsed between blood donation and diagnosis of the case, In univ ariate analysis, testosterone was positively associated with breast ca ncer risk (odds ratio (OR) for the highest quartile=2.7, 95% confidenc e interval (CI) 1.1-6.8, p <0.05, test for trend), However, after incl uding % estradiol bound to sex hormone-binding globulin (SHBG) and tot al estradiol in the statistical model, the odds ratios associated with higher levels of testosterone were considerably reduced, and there wa s no longer a significant trend (OR for the highest quartile=1.2, 95% CI 0.4-3.5). Conversely, breast cancer risk remained positively associ ated with total estradiol levels (OR for the highest quartile=2.9, 95% CI 1.0-8.3) and negatively associated with % estradiol bound to SHBG (OR for the highest quartile=0.05, 95% CI 0.01-0.19) after adjustment for serum testosterone levels. These results are consistent with the h ypothesis that testosterone has an indirect effect on breast cancer ri sk, via its influence on the amount of bioavailable estrogen. No evide nce was found of an association between DHEAS and risk of breast cance r in postmenopausal women.