Five years from now European cancer specialists should finally know whether anti-oestrogen drugs such as tamoxifen and raloxifene can prevent breast cancer and save the lives of women at high risk of the disease.
Professor Trevor Powles from the UK's Royal Marsden Hospital in Surrey told a news conference at the European Breast Cancer Conference in Brussels that an overview of all the current trials of tamoxifen and raloxifene will be possible in 2005.
This will allow full evaluation of the long-term effects of tamoxifen and the newer drug raloxifene on breast cancer incidence and mortality, and of the drugs' side-effects. It should also be possible to identify which sub-groups of healthy women can gain clinical benefit from these drugs.
"Until this is known, the general opinion of cancer specialists in Europe is that it is not possible to identify any risk groups of healthy women in whom use of tamoxifen or raloxifene prophylaxis is justified at this time outside of clinical trials. That's why it has not yet been licensed in Europe for use in a preventive setting."
He said that in the United States, tamoxifen has been approved by the Food and Drugs Administration for risk reduction in healthy women at high risk - the criteria in the US being women who had two-thirds increased risk over ten years. The FDA had come to this decision after the 13,000-women US trial was stopped early when an interim analysis in 1998 showed a 49% reduction in the incidence of early breast cancer in those who took tamoxifen compared with those who took the placebo.
But European experts are more cautious as the interim analysis of trials at the Royal Marsden and in Italy failed to show a similar effect - probably because there were differences in the risk factors and characteristics of the women in the three trials.
"The US results are very encouraging and indicate that there is a real chance that tamoxifen can prevent cancer and hopefully give rise to long-term clinical benefit. But lack of mortality data from the US trial and any data pointing to clinical benefit from the reduced incidence, together with indications we have from the Italian and Royal Marsden trial that there may be groups of women who are tamoxifen-resistant, raises concerns about its widespread use in healthy women at present. That's why we need to continue to recruit to the European trials and follow-up the participants over time."
Professor Powles said that whatever the outcome of these two trials prospects for eventual chemoprevention of breast cancer using designer drugs looked bright.
"We already have clinical evidence that raloxifene does not have the side effect of increasing the risk of endometrial cancer, which is one of the drawbacks of tamoxifen. In addition it has been shown to reduce fractures arising from osteoporosis: so the time is approaching when we will have drugs that can prevent breast cancer but without unwanted side-effects.
"Up to now there has been very little we can offer women at high risk except more frequent checks and screening - and for those at very high risk - the drastic step of preventive mastectomy. I'm confident that situation will change within the next few years," said Professor Powles.
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