Tamoxifen risk and benefits still inconclusive

Yet another clinical trial of tamoxifen can’t decide if the drug is worth taking.

Originally hailed as a major contribution to breast cancer prevention, tamoxifen has had a bumpy ride since AstraZeneca first launched it more than 15 years ago.

Before the latest trial, three separate clinical research groups, one in the USA and two in Europe, had already put the drug to the test – with mixed results. While a 50 per cent decrease in breast cancer was reported in the US, the European trials showed ‘little or no’ benefit from the drug.

Now, the results of a fourth investigation have just been announced by a UK cancer research team. For five years, over 7000 women aged 35-70 were given either 20 mg of tamoxifen a day or a placebo. At the end of the trial in January 2002, a total of 180 women (2.5 per cent) had contracted breast cancer.

At first sight, the results appeared to be marginally favourable to tamoxifen as 69 women taking the drug had succumbed to the disease, but 101 women in the placebo group had too.

However, when the researchers looked at death rates, the situation was totally reversed. More than twice as many women died with tamoxifen as with placebo.

The researchers said the drug’s side-effects could be the reason. During the trial, tamoxifen was found to cause severe gynaecological problems, resulting in an unusually high rate of womb and ovary removal.

But the most damaging side-effect was the appearance of blood clots, and these were apparently responsible for every one of the deaths among the group of women taking the drug.

Small wonder that the researchers concluded that ‘the overall risk to benefit ratio for the use of tamoxifen in breast cancer prevention is still unclear’ (Lancet, 2002; 360: 817-24).