Estrone and estradiol metabolism in vivo in human breast cysts

Fibrocystic disease of the breast manifesting palpable cysts express breast cyst fluids frequently containing estrogen sulfates at concentrations far exceeding those found in sera of the patient. The study explored the potent ial of the breast cyst to synthesize some of these estrogen sulfates. Deute rated estrone and estradiol were synthesized and either (estradiol, 4 cases or estrone, 2 cases) was injected into a cyst. The cyst was aspirated at a pproximately 0, 4 and 8 h, the target being 1 ml, 50% and complete aspirati on respectively. Metabolites were purified sequentially by ether extraction , enzymatic hydrolysis of estrogen conjugates, chromatography on Sephadex L H 20 and identified by gas chromatography linked to mass spectrometry. The unconjugated fraction isolated from the ether extract was subjected to the same purification and detection scheme. Among the conjugates, deuterated es trone sulfate was the major metabolite of either precursor in all studies, while estradiol sulfate was not detected in any of the 6 experiments. The s ulfate fractions also yielded traces of 16 alpha -hydroxyestrone (2 studies ), 4-hydroxyestrone (4 studies) and 2-hydroxyestrone (1 study). in the unco njugated fraction, one study with deuterated estradiol, 4-hydroxyestrone wa s obtained. In one study with deuterated estrone, traces of 2-hydroxyestron e and 16 alpha -hydroxyestrone were obtained. These novel data are signific ant because patients with fibrocystic disease are at slightly elevated risk for developing breast cancer and 16 alpha -hydroxyestrone and 4-hydroxyest rone are reported carcinogens. (C) 2000 Elsevier Science Inc. All rights re served.