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Effects of Tamoxifen on Estrogen and Progesterone Receptors in Human Breast Cancer¹

Second Medical Clinic, Department of Medicine, Kyoto University Faculty of Medicine, Kyoto 606, [N. W., Y. K., H. I.], and Department of Surgery, Kitano Hospital, Osaka 530 [M. K.], Japan

Twenty patients with primary breast cancer were treated with tamoxifen (10 mg p.o. twice a day) for 1 to 4 weeks. Before and after the tamoxifen administration, tumor specimens were obtained and assayed for estrogen receptors and progesterone receptors (PGR). Total cytosol estrogen receptor (ERC) and occupied nuclear estrogen receptor (ERN) were measured by hydroxylapatite assay, and unoccupied PGR was measured by the dextran-coated charcoal assay. ERC, ERN, and PGR were detectable in 11, 8, and 6 tumors, respectively, before tamoxifen administration. After tamoxifen treatment, ERC decreased in 10 of 11 ERC-positive tumors. Occupied ERN increased in three of five ERN-positive tumors treated with tamoxifen for a short period (1 to 2 weeks), but they decreased in all of three ERN-positive tumors after longer administration (3 to 4 weeks). PGR increased in three of five ERN-positive tumors after short-term tamoxifen treatment, but they decreased in all of three tumors treated by the drug for a longer period. Increased PGR responses were accompanied by an increase of ERN in two of three ERN-positive tumors. These results suggest that tamoxifen interacts with the estrogen receptor system in human breast cancer tissue and may be estrogenic during short treatment, while longer treatment results in an antiestrogenic response.

¹ This work was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education, Science, and Culture and the Ministry of Health and Welfare, Japan.

² To whom requests for reprints should be addressed.

Received 7/23/80. Accepted 2/ 4/81.

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