Actions of oestrogens and antioestrogens on rat mammary gland development: relevance to breast cancer prevention.

The proliferative actions of a series of antioestrogens on the development of the second thoracic mammary gland of ovariectomized immature Sprague-Dawley rats have been investigated. Evidence is presented that shows trans-tamoxifen, LY 117018 and LY 139481, like oestradiol-17 beta and cis-tamoxifen, promote full mammary gland ductal development and induce a high rate of cell proliferation in the undifferentiated epithelial cells of the terminal end buds, the main growth region for ductal growth. Conversely, ICI 164,384, a new antioestrogen, is without effect on ductal elongation. In vivo exposure of trans-tamoxifen and LY 117018 treated glands in medically castrated animals to the carcinogen DMBA, results in a high rate of mammary tumour development. Indeed, the actions of these so-called antioestrogens are equivalent to those observed in oestradiol-treated rats.