Breast cancer drug raises new fears: Benefit of treatment tried on thousands of women under question

THE CONTROVERSIAL research programme, just starting in this country, to give healthy but 'at risk' women the drug, tamoxifen, to prevent breast cancer has hit another obstacle.

A report in tomorrow's edition of the Lancet has found further evidence that the drug increases the risk of cancer of the lining of the womb, the endometrium.

While the benefits of tamoxifen still outweigh the risks for those women already diagnosed as having breast cancer, the researchers warn that the benefits may not be so apparent in women who are still healthy but at future risk from breast cancer.

'It is debatable whether the use of a medical intervention can be justified when it prevents breast cancer in some women at the cost of inducing endometrial cancer in others,' according to Flora van Leeuwen, an epidemiologist working at the Netherlands Cancer Institute in Amsterdam.

In their study of endometrial cancer, the Dutch researchers found that women who had been taking tamoxifen for more than two years were more than twice as likely to develop endometrial cancer than those not taking the drug. The risk increased with time and the amount taken. Women taking the drug for more than five years were three times more likely to have endometrial cancer.

Tamoxifen was introduced in the Seventies to treat advanced breast cancer and more recently has been found to be very effective in keeping women with early breast cancer disease-free, and for women over 50 with this disease.

The new international trial, which is intended to involve thousands of women in 14 countries, has already begun in the United States, Australia, Italy and Switzerland. Last July, the Department of Health sanctioned the study in 18 British centres, involving 15,000 patients. Women are beginning to be recruited in this country, starting in Manchester. Volunteers in London will be sought shortly.

The plan is to give tamoxifen to healthy women who have a two or three times higher risk of breast cancer than normal because of family history and it is being organised here by the United Kingdom Co-ordinating Committee on Cancer Research. However, the Medical Research Council refused to join the study because of evidence that tamoxifen caused liver cancer in rats; it is conducting its own toxicity studies.

Yesterday, Dr Jack Cuzick, of the Imperical Cancer Research Fund and chairman of the international trialists' group, said that the researchers knew of the Dutch work and had discussed it at a meeting in January.

'An expert monitoring committee is meeting regularly to evaluate all new data that might have a bearing on this study,' he said.

He said that Dr van Leeuwen's findings showed a lower risk level than they had allowed for in their prevention study.

'We have been working on the possibility of a threefold risk. This level means that over the five years the women in the trial are taking tamoxifen, their risk of developing endometrial cancer rises from 2 per 1,000 women to 5 per 1,000,' Dr Cuzick said.

'We are not underestimating the importance of this risk factor - certainly for the individual women who develop endometrial cancer it is very important indeed.

'But we do not see it as a reason for denying the option of taking part in the trial to the women at increased risk of breast cancer. They are being informed of the potential risks as well as the potential benefits,' he said.