Comparison of the effects of EM-652 (SCH57068), tamoxifen, toremifene, droloxifene, idoxifene, GW-5638 and raloxifene on the growth of human ZR-75-1 breast tumors in nude mice

Authors

  • Matthieu Gutman,

    1. Oncology and Molecular Endocrinology Research Center, Laval University Medical Center and Laval University, Quebec, Canada
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    • The first 2 authors contributed equally to this work.

  • Steeve Couillard,

    1. Oncology and Molecular Endocrinology Research Center, Laval University Medical Center and Laval University, Quebec, Canada
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    • The first 2 authors contributed equally to this work.

  • Jenny Roy,

    1. Oncology and Molecular Endocrinology Research Center, Laval University Medical Center and Laval University, Quebec, Canada
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  • Fernand Labrie,

    1. Oncology and Molecular Endocrinology Research Center, Laval University Medical Center and Laval University, Quebec, Canada
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  • Bernard Candas,

    1. Oncology and Molecular Endocrinology Research Center, Laval University Medical Center and Laval University, Quebec, Canada
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  • Claude Labrie

    Corresponding author
    1. Oncology and Molecular Endocrinology Research Center, Laval University Medical Center and Laval University, Quebec, Canada
    • Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, 2705 Laurier Boulevard, Quebec, G1V 4G2, Canada
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    • Fax: +418-654-2761


Abstract

EM-652 exerts pure antiestrogenic activity in the mammary gland and endometrium, while tamoxifen, the antiestrogen most widely used for the treatment of breast cancer, exerts mixed antiestrogenic–estrogenic activity in these tissues. Our objective was to compare the agonistic and antagonistic effects of EM-652 with tamoxifen and 5 other antiestrogens on the growth of ZR-75-1 human breast xenografts in ovariectomized nude mice. During the 23 weeks of treatment at a daily oral dose of 50 μg, EM-652 was the only compound that decreased tumor size relative to pretreatment values, whereas the 6 other antiestrogens only decreased to various extents the progression rate stimulated by estrone. Under estrone stimulation, all groups of animals had more than 60% of their tumors in the progression category except for the EM-652–treated group, where only 7% of the tumors progressed. In the absence of estrone stimulation, progression was seen in 60%, 33%, 21% and 12% of tumors in the tamoxifen-, idoxifene-, toremifene- and raloxifene-treated groups, respectively, while only 4% of tumors progressed in the EM-652–treated group. The agonistic and antagonistic actions of each antiestrogen were also measured on endometrial epithelial cell thickness. Our present findings indicate that EM-652, in addition to being the most potent antiestrogen on human breast tumor growth, has no agonistic effect in breast and endometrial tissues. Since previous data have shown benefits of EM-652 on bone density and lipid profile, this compound could be an ideal candidate for chemoprevention of breast and uterine cancers, while protecting against osteoporosis and cardiovascular disease. © 2002 Wiley-Liss, Inc.

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