ACTIVITY OF TAMOXIFEN AND NEW ANTIESTROGENS ON ESTROGEN-RECEPTOR POSITIVE AND NEGATIVE BREAST-CANCER CELLS

The effect of some new antiestrogens (ICI 164384, ICI 182780, Ly 13331 4 and Ly 117018) on the growth of a panel of breast cancer cell lines (MDA-MB 231 ,BT20, MCF7 and T47D) was studied Their antiestrogenic act ivity was investigated in the presence of a physiologic concentration of estradiol and compared with the effect displayed by tamoxifen in th e same experimental conditions. Tamoxifen confirmed its antagonistic a ctivity in the presence of estradiol, whereas when given alone it did not exhibit a clear antiproliferative effect. All other compounds show ed variable activity: ICI 164384 and ICI 182780 exerted a variable inh ibitory effect in all cell lines, but only in the absence of estradiol ; Ly 133314 and Ly 117018 did not show a clear antagonistic activity a nd sometimes had a synergistic effect with estradiol in increasing cel l growth. These results indicate an extreme variability in terms of an tagonistic effect of these new compounds and suggest their inadequacy to replace tamoxifen as an antiestrogen during endocrine treatment. In terestingly, ICI 164384 exerted antiproliferative action also on estro gen receptor-negative cell lines, probably through an alternative mech anism non estrogen receptor-mediated, supporting the hypothesis that i t could be effective on estrogen receptor positive as well as estrogen receptor-negative tumors.