INFLUENCE OF DIFFERENT COMBINATIONS OF TAMOXIFEN AND TOREMIFENE ON ESTROGEN RECEPTOR-POSITIVE BREAST-CANCER CELL-LINES

Acquired tamoxifen (TAM) resistance is supposed to be the major cause of hormone therapy failure in estrogen receptor (ER)-positive breast c ancer patients. Toremifene (TOR), a chlorinated TAM-related compound, has been found to be more effective and less toxic than TAM. Moreover, 4-hydroxy-toremifene (OH-TOR), like 4-hydroxy-tamoxifen (OH-TAM), is the most effective metabolite in humans. To better understand the rela tive role of TAM, TOR, OH-TAM, and OH-TOR, singly or in combination, w e studied their effect on MCF7, ZR-75.1, and T47D cell lines, which, d espite their positive receptor status, have a different responsiveness to estradiol and antiestrogenic compounds. The results may be summari zed as follows: in MCF7 cells, all compounds, singly or in association , showed an inhibitory effect; ZR75.1 cells were resistant to TAM and OH-TAM, but partially sensitive to TOR and OH-TOR; in T47D cells, all compounds displayed their estrogenic activity and induced cell growth. These results suggest the inefficacy of these triphenylethylene deriv atives as a hormone treatment even when given in a simultaneous or seq uential combination.