Anti-oestrogenic and anti-tumour properties of prolonged tamoxifen therapy in C3H/OUJ mice

The anti-oestrogenic and anti-tumour properties of a sustained-release preparation of tamoxifen were evaluated in female C3H/OUJ mice. Tamoxifen decreased uterine weight compared with controls in intact mice but caused an initial uterotrophic response for 2 months in ovariectomized mice. Prolonged tamoxifen therapy in ovariectomized mice resulted in a uterine weight no different from controls, but these uteri were eventually (at 6 months) refractory to oestradiol. Spontaneous mammary tumours were detected in female mice between 6 months and 1 year of age during continuous cycles of pregnancy and weaning. A similar tumour frequency occurred after one cycle of pregnancy and weaning initiated at 3 1 2 months. Prolonged tamoxifen, started at 3 1 2 or 4 1 2 months of age (following pregnancy/weaning), reduced the appearance of tumours. Similarly ovariectomy at 3 1 2 months prevented mammary tumorigenesis and prolonged tamoxifen could not increase tumour incidence consistently in ovariectomized mice. Although tamoxifen is oestrogenic in short-term tests the compound has the properties of an anti-oestrogen during prolonged administration.