Q:Can you tell me about the risks of tamoxifen for women at risk of developing breast cancer? C. H., London.
A:Tamoxifen, which has been used to treat women with breast cancer for nearly 20 years, is now on trial for possible liver toxicity. As you may know, in February, the Committee on Safety of Medicines approved the use of tamoxifen for use on 16,000 healthy women considered to have a risk of contracting breast cancer in the future. A trial has been planned by the Imperial Cancer Research Fund and the Cancer Research Campaign to see whether the drug could prevent cancer, with the blessing of the Medical Research Council.The MRC has recently withdrawn its support for the trial for anyone other than women over 40 with a fourfold or greater relative risk of breast cancer. This means a woman with a first degree relative with breast cancer on both breasts or two first degree relatives with breast cancer, those with existing cancer or those with "hyperplasia" ie, abnormal cells that have not yet progressed on to cancer.
The reason for their misgivings has to do with the 20 mg per day dosage proposed for the trial. This dosage is considered equivalent to one that has caused highly malignant liver tumours in rats. It also caused DNA mutations in the animals after receiving the drug for at most six doses (and sometimes only one).
Although there is not enough data on the effects of the drug in the livers of man, there have been some suspicious findings. One Swedish trial, published in the Lancet, showed two cases of liver tumours. There are also associations between the drug and problems of the retina of the eye. All of these suspicions have caused the MRC to ask its toxicology unit to investigate the toxicity of the drug as a matter of urgency. The trial will now proceed without the MRC.
Says Dr Dai Rees, MRC secretary: "The MRC has no wish to spread alarm among women taking tamoxifen for proven cases of breast cancer. . . The trial in question seeks to use the drug in well women. We have taken the view that until more evidence is obtained to inform better risk/benefit calculations the best course is to proceed with caution."
Among those who do have breast cancer, studies have shown that tamoxifen seems to reduce the rate of recurrence and death among women over 50 who take it. It also may reduce the risk of cancer in the well breast by 40 per cent, according to a study in the Lancet in January. Nevertheless, its benefits for young women have never been proved. Furthermore, one of the problems is that you need to take the drug for at least five years. This could cause a number of other problems, including secondary cancers.
Because the drug has oestrogen antagonist properties (reactions that reduce oestrogen, which is thought to aid tumour growth), one worry was that it might lower bone density in older women. A recent trial (New England Journal of Medicine, 26 March 1992) showed that it actually has a slightly favourable effect on bone density.
Nevertheless, nearly half the women taking tamoxifen report symptoms similar to those experienced in the menopause (hot flushes and vaginal dryness); 10 per cent quit the drug because they find the side effects unacceptable. The drug has also been associated with stroke or blood clots in 1 to 2 per cent of patients.
Finally, there is the risk of other cancers developing in other parts of the body. At least one trial in the Lancet (1989) showed an increase in endometrial cancer in women undergoing long term treatment with tamoxifen.
Whether or not you should take this drug depends on many variables, including your age, and whether you actually have breast cancer. If you haven't developed cancer it certainly seems prudent to avoid taking it, as a New England Journal editorial (same issue as above) suggests, until the trial on healthy women is completed. If you do decide to go ahead, make sure that your doctor closely monitors your liver, eyes and various reproductive organs for possible problems or tumours.