Article

Overview of the main outcomes in breast-cancer prevention trials

Cancer Research UK, London, UK.
The Lancet (Impact Factor: 39.21). 01/2003; 361(9354):296-300. DOI: 10.1016/S0140-6736(03)12342-2
Source: PubMed

ABSTRACT Early findings on the use of tamoxifen or raloxifene as prophylaxis against breast cancer have been mixed; we update available data and overview the combined results.
All five randomised prevention trials comparing tamoxifen or raloxifene with placebo were included. Relevant data on contralateral breast tumours and side-effects were included from an overview of adjuvant trials of tamoxifen versus control.
The tamoxifen prevention trials showed a 38% (95% CI 28-46; p<0.0001) reduction in breast-cancer incidence. There was no effect for breast cancers negative for oestrogen receptor (ER; hazard ratio 1.22 [0.89-1.67]; p=0.21), but ER-positive cancers were decreased by 48% (36-58; p<0.0001) in the tamoxifen prevention trials. Age had no apparent effect. Rates of endometrial cancer were increased in all tamoxifen prevention trials (consensus relative risk 2.4 [1.5-4.0]; p=0.0005) and the adjuvant trials (relative risk 3.4 [1.8-6.4]; p=0.0002); no increase has been seen so far with raloxifene. Venous thromboembolic events were increased in all tamoxifen studies (relative risk 1.9 [1.4-2.6] in the prevention trials; p<0.0001) and with raloxifene. Overall, there was no effect on non-breast-cancer mortality; the only cause showing a mortality increase was pulmonary embolism (six vs two).
The evidence now clearly shows that tamoxifen can reduce the risk of ER-positive breast cancer. New approaches are needed to prevent ER-negative breast cancer and to reduce the side-effects of tamoxifen. Newer agents such as raloxifene and the aromatase inhibitors need to be evaluated. Although tamoxifen cannot yet be recommended as a preventive agent (except possibly in women at very high risk with a low risk of side-effects), continued follow-up of the current trials is essential for identification of a subgroup of high-risk, healthy women for whom the risk-benefit ratio is sufficiently positive.

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