Non-steroidal antioestrogens--receptor binding and biological response in rat uterus, rat mammary carcinoma and human breast cancer cells.

The non-steroidal antioestrogens tamoxifen, 4-hydroxytamoxifen, trioxifene, LY 117018 and LY 139481 have widely divergent affinities for oestrogen receptors from rat mammary tumours. The latter two compounds have much reduced partial agonist activity in rat uterus, compared to tamoxifen, but were less effective antitumour agents than tamoxifen. No direct correlation was established between receptor affinity and biological response in rat uterus or rat mammary carcinoma. However, in in vitro studies of growth inhibition of human breast cancer cells (MCF7), the order of potency was the same as the order of relative binding affinity. Differences in in vivo activity of these antioestrogens may be related to biological "half-life" which is dependent on the dose, route of administration and metabolic stability of the antioestrogens. Growth inhibition in MCF 7 cells did not correlate with affinity for tamoxifen-specific binding sites, nor was there any evidence for differences between antioestrogens in their mechanism of action on the rat uterus. It is concluded that the primary effects of antioestrogens are mediated by binding to oestrogen receptors.