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Long‐term inhibitory effect of the orally active and pure antiestrogen EM‐800 on the growth of human breast cancer xenografts in nude mice
Author(s) -
Couillard Steeve,
Labrie Claude,
Gauthier Sylvain,
Merand Yves,
Singh Shankar Mohan,
Candas Bernard,
Labrie Fernand
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000201)85:3<424::aid-ijc20>3.0.co;2-s
Subject(s) - antiestrogen , medicine , cancer , inhibitory postsynaptic potential , breast cancer , tamoxifen , oncology , orally active , mammary gland , cancer research , endocrinology , oral administration
The antiproliferative effect of the new antiestrogen EM‐800 has been studied during 40 weeks of treatment on human breast carcinoma ZR‐75–1 xenografts in ovariectomized nude mice supplemented with estrone (0.5 μg, s.c. daily). At the daily 50 μg (approximately 2.5 mg/kg) oral dose, EM‐800 caused a complete inhibition of the 680% stimulatory effect of estrone on the growth of the ZR‐75–1 human breast cancer xenografts. Complete response, defined as the complete disappearance of the tumors, was observed in 41% of tumors following treatment with the 50 μg dose of the antiestrogen, while a value of 26% was found in ovariectomized animals. The proportion of tumors showing progression at the end of 40 weeks of treatment decreased from 94% in the estrone‐supplemented animals to 62%, 61% and 19% in the animals receiving the 5 μg, 20 μg and 50 μg daily doses of the antiestrogen, respectively. None of the tumors that showed a complete or a partial response progressed at later time intervals. The 50 μg daily dose of EM‐800 nearly completely (93%) or completely (28% below the value in ovariectomized animals) reversed the stimulatory effect of estrone on uterine and vaginal weight, respectively. The disappearance of 41% of tumors in the group of animals that received the 50 μg daily dose of EM‐800 indicates that the antiestrogen induces cell death or apoptosis in ZR‐75–1 human breast cancer cells and that its action is cytotoxic and not only cytostatic. Int. J. Cancer 83:424–429, 2000. ©2000 Wiley‐Liss, Inc.