TAMOXIFEN INDUCED APOPTOSIS IN ZR-75 BREAST-CANCER XENOGRAFTS ANTEDATES TUMOR-REGRESSION

The ZR-75-1 ER positive breast cancer cell line, xenografted in female nude mice, has been used to determine the effect of tamoxifen on cell proliferation (as measured by mitosis) and cell death (as evidenced b y apoptosis and necrosis). After 2 days treatment, there was a signifi cant rise in apoptosis (p < 0.05), whereas a fall in mitosis was not a pparent until 7 days (p < 0.05). Furthermore there was an increase in the apoptotic : mitotic ratio on day 7 (p < 0.05). These changes anted ated tumour regression, which did reach not significance until day 14. Tamoxifen did not increase necrosis (which significantly decreased in treated tumours once they had regressed (p < 0.01)). In contrast tamo xifen treatment of xenografted MDA-MB-231 ER-negative breast cancer ce lls produced no significant effects on growth, apoptosis, or mitosis. This study presents clear evidence for tamoxifen inducing apoptosis in ZR-75-1 xenografts (but not MDA-MB-231 tumours). Since changes in apo ptosis and mitosis antedate tumour regression, their assessment may pr ovide the potential by which to predict tumour response to tamoxifen t herapy.