Athymic nude mouse model for the study of new antioestrogens in breast cancer

Endocrine therapy utilizing agents that reduce oestrogen levels or block the oestrogen receptor remains an important modality in breast cancer management. While hormonal treatments are effective in many patients, de novo and acquired resistance are common problems. Model systems are needed that mimic the clinical situation to facilitate studies of the mechanisms of hormonal resistance. We have developed an in vivo model system for studies of endocrine therapy using the ER-positive MCF-7 human breast cancer cells growing subcutaneously in athymic mice. Similar to observations in patients, treatment of these mice by oestrogen withdrawal, tamoxifen, or steroidal antioestrogens (which have a pure antioestrogenic profile), inhibits growth of established tumours for several months. Eventually, tumours develop resistance and progression occurs. The steroidal antioestrogens offer more prolonged tumour control compared to tamoxifen and oestrogen withdrawal. Furthermore, these antioestrogens inhibit tumours that have developed resistance to oestrogen deprivation and/or tamoxifen. Studies from this model system support the hypothesis that pure steroidal antioestrogens may be effective antitumour agents in patients and that they may be useful in patients with tamoxifen resistance.