Antiestrogens mammary glands

Labrie F, Labrie C, Belanger A, Simard J, Gauthier S, Luu-The V, et al. (1999) EM-652 (SCH 57068), a third generation SERM acting as pure antiestrogen in the mammary gland and the endometrium. J Steroid Biochem Mol Biol 69 51-84... 

E. Need of an Antiestrogen Having Pure Antiestrogenic Activity in the Mammary Gland and Endometrium... 

The steroidal antiestrogens ICI 164,384, ICI 182,780, and EM-139 are devoid of estrogenic activity in the mammary gland, uterus, and hypothalamic-pituitary-ovarian axis (Labrie et al., 1992b Wakeling and Bowler, 1988b). 

Stimulated by the need for an improved therapy for breast cancer, considerable efforts have been devoted to the synthesis of compounds that would exert pure antiestrogenic activity in the mammary gland and uterus. As mentioned above, while tamoxifen has beneficial effects on breast cancer, it clearly acts as an estrogen agonist in the endometrium, leading to an increased rate of endometrial carcinoma in women taking tamoxifen under chronic conditions. Moreover, it is most likely that a pure antiestrogen will have beneficial effects superior to those of tamoxifen in breast cancer prevention and treatment. 

The present data clearly demonstrate that in the rat, low doses of EM-800 prevent bone loss and lower serum cholesterol levels without stimulatory effect on the endometrium, and previous studies have described the pure antiestrogenic activity of this compound in the mammary gland. Such data are encouraging and suggest that the antiestrogen EM-652 and its precursor EM-800 have the potential for exerting simultaneous beneficial effects on four important aspects of women s health, namely, prevention and/or treatment of breast and uterine cancer, osteoporosis, and coronary heart disease. 

In ovariectomized rats administered 250, 500, or 750 mg daily of a red clover extract (15% isoflavones) for 21 days, a dose-dependent increase in uterine weight and differentiated vaginal cells were observed at the two higher doses, but no stimulation of cell proliferation was observed in the mammary glands. Neither antiestrogenic nor additive estrogenic properties were observed in any of the tissues studied (Burdette et al. 2002). 

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