HUMAN RECOMBINANT INTERFERON-BETA(SER) AND TAMOXIFEN - GROWTH SUPPRESSIVE EFFECTS FOR THE HUMAN BREAST-CARCINOMA MCF-7 GROWN IN THE ATHYMICMOUSE

Tamoxifen is the endocrine treatment of choice for breast cancer. Howe ver, resistance to therapy and patient relapse inevitably occurs. In f uture treatment schedules, interferons could be administered with tamo xifen, in an attempt to prevent disease recurrence. Human recombinant interferon-beta(SER) (rIFN-beta(SER) inhibited the growth in vitro of the estrogen receptor (ER) positive breast cancer cell line MCF-7 and the ER negative breast cancer cell line MDA-MB-231. This inhibitory ef fect was achieved at doses of 50 U/ml and above. The growth of MCF-7 t umors in estradiol-stimulated athymic mice was greatly inhibited by hi gh dose rIFN-beta(SER) treatment (10(6)U/day). In spite of the impress ive antitumor effects upon MCF-7 tumors, rIFN-beta(SER) had no effect upon ER levels within the tumors at either the RNA or protein level, a s measured by Northern blotting and ER-EIA respectively. High dose rIF N-beta(SER) (10(6) U/day) did result in some inhibition in the growth in vivo of the tamoxifen-stimulated MCF-7 variant MCF-7 TAM, although not to the same extent as was observed with the estradiol-stimulated M CF-7 tumors. rIFN-beta(SER) was also administered to animals bearing M CF-7 tumors and treated with estradiol and tamoxifen. In the animals u ndergoing high dose therapy (10(6) U/day), tumor growth was completely suppressed. Furthermore, tumor growth continued to be suppressed in t hose animals in which the rIFN-beta(SER) therapy was halted and the ta moxifen capsule removed. No tumors were observed in spite of the envir onment of estradiol stimulation. Thus, the combination of interferon a nd tamoxifen was totally growth suppressive for MCF-7 xenografts in nu de mice.