| Abstract
| - Patients with advanced breast cancer were treated with antiestrogen, tamoxifen, 20 mg orally, twice a day. Of the evaluable 23 patients, one achieved complete response with a duration of 16 months, and five achieved partial response lasting from two to eight months, indicating that the response rate was 26%. In the five peri-and postmenopausal patients, basal and LH-RH stimulated plasma LH levels decreased but stayed within the postmenopausal range in three patients during the tamoxifen therapy. Basal and LH-RH stimulated FSH levels decreased also but stayed within the postmenopausal range in all five patients. In a premenopausal patient, basal and stimulated plasma LH and FSH levels did not change significantly during the tamoxifen therapy. The plasma TSH responses did not change significantly. In three of the six patients, basal and TRH-stimulated prolactin levels decreased slightly during the tamoxifen therapy. These relatively inconsistent and small changes in the pituitary hormone secretion observed during the tamoxifen therapy suggest that the anti-tumor effect of tamoxifen was not due to alteration of the pituitary hormone secretion. The binding of tamoxifen for the estrogen receptor was examined in the estrogen receptor assay system. The dose response curve for tamoxifen was parallel to that for estradiol, indicating that tamoxifen competes with estradiol for the estrogen receptor. The affinity constants of tamoxifen for the estrogen receptor in eight cytosols of human breast cancer tissues were (139 ±79) X 10−10M (mean±SD), indicating that the binding affinity of tamoxifen was about 0.7% that of estradiol. The affinity constants for nuclear receptors were similar to those for cytosol receptors. These data suggest that tamoxifen is a useful drug for treatment of advanced breast cancer, and that the anti-tumor effect could be related to its binding to estrogen receptors in tumor tissues, and not caused by altering the secretion of pituitary hormones.
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