The use of tamoxifen as a preventive agent against breast cancer in healthy women has been questioned by Dutch researchers.
In a study published in this week's Lancet (2000;356:881), they say that prognosis of endometrial cancer is worse in long-term users of tamoxifen than in non-users. While in patients with breast cancer the benefit of tamoxifen outweighs this risk, this may not be the case in healthy women who take tamoxifen as a preventive measure, they say.
The study of 309 women who developed endometrial cancer after breast cancer and 860 matched controls who had breast but not endometrial cancer was conducted by Dr Leisbeth Bergman (department of epidemiology, Netherlands cancer institute, Amsterdam) and colleagues, on behalf of the ALERT (assessment of liver and endometrial cancer risk following tamoxifen) group. Information on tamoxifen use and other risk factors was obtained for each patient from medical records.
The researchers found that the risk of endometrial cancer in breast cancer patients taking tamoxifen increased with duration of use, irrespective of daily dose. Little evidence was found that the excess risk disappeared after cessation of treatment and they suggest that the effects of tamoxifen could last for several years once treatment is stopped.
While it was known that tamoxifen was associated with an increase in risk of endometrial cancer, it had been assumed that tamoxifen-related tumours were early stage, well-differentiated and prognostically favourable, the researchers comment. However, they found that endometrial tumours developed after long-term use of tamoxifen seemed to be prognostically worse than those in patients who had not taken tamoxifen. In addition, tamoxifen users were more likely to die from endometrial cancer than non-users. They add that tamoxifen's mechanism of action on the endometrium is not fully understood but is probably oestrogen-receptor dependent. They conclude: "We do not think that this unexpected result has consequences for the treatment of breast cancer patients because the survival benefits of tamoxifen for breast cancer far outweigh the adverse effects. . . However, our finding of a less favourable prognosis of endometrial cancer after long-term tamoxifen use suggests the need to question widespread use of the drug as a preventive agent in healthy women at increased risk of breast cancer."