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Effect of tamoxifen treatment on estrogen metabolism in postmenopausal women with advanced breast cancer.

The effect of tamoxifen therapy on plasma estrone and estradiol concentration, urinary excretion of estrone, estradiol, and estriol glucuronides, and metabolism of a tracer of 3H-estradiol was studied in 12 postmenopausal women with metastatic breast cancer. The most striking change observed was consistent increase in the 72-hour urinary recovery of total radioactivity after the tracer, from a mean of 47% to a mean of 61% of the dose. This increase was accounted for by a corresponding increase in the recovery of total glucuronide radioactivity, from a mean of 32% to a mean of 44% of the dose; there was no change in the proportions of estrone, estradiol, estriol, or 2-hydroxyestrone in the glucuronide fraction. The most likely explanation for this finding is that the estrogen-receptor-blocking effect of tamoxifen decreases estrogen uptake by various tissues and permits the estrogen to be excreted in the urine instead. There was also a small but consistent and significant decrease in plasma estrone (from 47 to 36 pg/ml) and estradiol (from 15 to 13 pg/ml), with no change in urinary excretion of estrogen glucuronides. The drop in plasma estrogen levels without a decrease in estrogen production suggests that tamoxifen may increase the metabolic and/or renal clearance of estrogen metabolites. There was no correlation between the observed effects of tamoxifen and the pretreatment estrogen-receptor status of the patient or her response to tamoxifen therapy.