The evolution of tamoxifen therapy in breast cancer: selective oestrogen-receptor modulators and downregulators.

Tamoxifen is the most widely used hormonal treatment for all stages of breast cancer and has been approved for the prevention of breast cancer in high-risk women. The observation that tamoxifen acts as an antioestrogen on the breast but has paradoxical oestrogenic effects on bones and lipids heralded the development of the selective oestrogen-receptor modulators (SERM). Raloxifene, another of these drugs, is being used to prevent osteoporosis in postmenopausal women, but it seems, like tamoxifen, to prevent breast cancer. The molecular basis for these target-site-specific actions remains unclear but may involve the relative expressions of coregulatory proteins in target tissues. Several new SERM agents are in clinical development in an attempt to decrease the unwanted effects. Furthermore, two different classes of hormonal agents, the aromatase inhibitors and oestrogen-receptor downregulators, which have no oestrogen-like properties at any site, are promising new treatments for breast cancer.