title: Long-term inhibitory effect of the orally active and pure antiestrogen EM-800 on the growth of human breast cancer xenografts in nude mice.
abstract: 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 microg, s.c. daily). At the daily 50 microg (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 microg 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 microg, 20 microg and 50 microg 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 microg 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 microg 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.
authors.affiliation: Oncology and Molecular Endocrinology Research Center, Centre Hospitalier Universitaire de Québec and Laval University, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Couillard
authors.forename: C
authors.initials: C
authors.lastname: Labrie
authors.forename: S
authors.initials: S
authors.lastname: Gauthier
authors.forename: Y
authors.initials: Y
authors.lastname: Merand
authors.forename: S M
authors.initials: SM
authors.lastname: Singh
authors.forename: B
authors.initials: B
authors.lastname: Candas
authors.forename: F
authors.initials: F
authors.lastname: Labrie
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D010052:Ovariectomy; D011422:Propionates / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D018931:Antineoplastic Agents, Hormonal; D001578:Benzopyrans; D020847:Estrogen Receptor Modulators; D011422:Propionates; C106945:EM 800