British and American researchers have adopted different approaches to trials into the drug tamoxifen as prevention against breast cancer. Why?

The Americans, finding tamoxifen gives a substantial benefit in protecting against breast cancer, stopped their trial. One result of this is that women who were taking placebo now have the chance to take tamoxifen if they and their doctors so choose. In the UK and other countries, researchers are continuing their trials, because they feel they need to find out whether the benefits of tamoxifen continue long term, and whether the benefits outweigh the long-term disadvantages.

Here, Professor Anthony Howell of Christie Hospital, Manchester, who is co-chairman of the British-based trial into tamoxifen, explains the issues involved, and why the British and other researchers feel it is important to continue with these trials.

Six years after its inception the US Breast Cancer Prevention Trial (BCPT) shows a 45% reduction in breast cancer incidence among high-risk participants who took tamoxifen. This is not completely surprising since the prevention trials are based on a similar reduction in second cancers in the opposite breast in breast cancer patients.

Over 13,000 women were randomised to receive five years of tamoxifen or placebo. After an average follow up of four years, women taking tamoxifen developed 85 cases of invasive breast cancer, compared to 154 cases in the women taking the placebo (a dummy treatment). The women taking tamoxifen also had slightly fewer fractures. On the down side, there were small increases in endometrial cancer (33 tamoxifen versus 14 placebo) and clots in leg veins and lungs (47 tamoxifen versus 25 placebo); these are well recognised side effects.

The real questions about the American results are: do the benefits of cancer reduction with tamoxifen outweigh the overall risks? Also, will the reduced incidence of cancer be sustained?

The long-term balance of risks and benefits will not be answered by the American trial since it has now been stopped. This adds to the importance of data from trials outside the Untied States. The IBIS (International Breast Cancer Intervention Society) has recruited no more than 4,300 subjects in the UK, Europe and Australia, the Italian trial approximately 6,000 subjects and the Royal Marsden Pilot Trial, started in 1986, 2,500 subjects.

Investigators in the IBIS trial have asked women to continue on their assigned treatment in order to discover the long-term risk benefit ratio of tamoxifen treatment. We have received very positive responses from participants, all of whom were told of the American results by letter as soon as they were published on the Internet. We plan to combine the results of the non-American trials. By the year 2000, we hope to have a more definite answer to the question of whether we can prevent breast cancer using tamoxifen.