Current prevention trials have shown that tamoxifen can reduce the incidence of breast cancer by about 30%-40% in high-risk women, but that the risk of thromboembolic disease and endometrial cancer are increased about twofold. An alternative approach for postmenopausal women is to use an aromatase inhibitor to reduce oestrogen to very low levels. Data from the ATAC adjuvant trial indicate that the aromatase inhibitor anastrozole is more effective than tamoxifen in reducing recurrence and preventing new contralateral tumours, and also has a more favourable side-effect profile. This has led us to launch a new prevention trial--IBIS-II--in 6,000 high-risk postmenopausal women comparing anastrozole against placebo. A parallel trial will compare anastrozole against tamoxifen in 4,000 women with locally excised DCIS.