Chemoprevention: beyond tamoxifen

Four trials have now reported on the use of tamoxifen for the prevention of breast cancer and one trial on the use of raloxifene. Overall, more than 28,000 women have participated in tamoxifen prevention trials and more than 140,000 women-years of follow up have accrued. Although early reports on the ability of tamoxifen to prevent breast cancer were apparently contradictory, with further follow up a consensus is now emerging indicating that 30–40% of breast cancers can be prevented by tamoxifen [1]. The benefit is restricted to oestrogen receptor positive tumours, where it is about 50%, but no reduction in receptor negative tumours has been found. Thrombo-embolic events are emerging as the most important side effects, and endometrial cancers are increased about twofold, although these are almost all low/intermediate grade, stage I cancers.

Raloxifene does not have the gynaecologic problems of tamoxifen, but still leads to an increase in thromboembolic events. Recent data from CORE/MORE [2] suggests that this selective oestrogen receptor modulator (SERM) may be more effective in prevention than tamoxifen. Six adjuvant trials have reported on the use of aromatase inhibitors for early breast cancer. All of them show a marked reduction in contralateral tumours compared with tamoxifen [3]. The drugs are also better tolerated and have fewer side effects than tamoxifen, suggesting that they are very promising agents for breast cancer prevention. These data will be reviewed and ongoing chemoprevention trials discussed.