Laboratory models of breast and endometrial cancer to develop strategies for antiestrogen therapy

Laboratory models for breast and endometrial cancer have had an enormous impact on the clinical development of antiestrogens. Results from the DMBA-induced rat mammary cancer model has provided the scientific principles required to evaluate long-term adjuvant tamoxifen therapy. Similarly, the athymic mouse model allowed the identification of clinically relevant mechanisms of drug resistance to tamoxifen and a model system to test new agents for cross resistance. Additionally, the endometrial cancer model has allowed the identification of agents that cause a slight increase in the risk of endometrial cancer long before the data would have be available from clinical studies. However, it should be stressed that this model is really only relevant for agents to be tested as preventives in normal women. The risks of developing endometrial cancer during tamoxifen therapy are slight compared with the survival benefit in controlling breast cancer.