Women who take tamoxifen to prevent breast cancer may want to reconsider, say Dutch researchers, who report that the drug boosts the risk of particularly virulent uterine tumors. The findings, which American scientists challenged, don't question the use of tamoxifen in women who already have breast cancer. Yet, Flora Van Leeuwen, the Dutch scientist who led the latest study, says tamoxifen may cause roughly one case of uterine cancer for every four cases of breast cancer it prevents. "In the prevention of serious diseases like cancer, to use drugs that can have fatal side effects is not a very good idea," says Van Leeuwen, of the Netherlands Cancer Institute in Amsterdam. A report on the study appears in The Lancet. Tamoxifen has been available as a treatment for breast cancer for more than 20 years. The drug counteracts the hormone estrogen, which spurs the formation of tumor cells -- leading some to call it an "anti-estrogen." A major American trial found that women who took tamoxifen cut their risk of breast cancer by about 45 percent compared to those who didn't use the drug. And in October 1998, the U.S. Food and Drug Administration approved a form of tamoxifen, Nolvadex, for the prevention of breast cancer. But British and Italian scientists couldn't confirm that effect in their own research, Van Leeuwen notes. "This publication should never be a reason for breast cancer patients to stop taking their medication," Van Leeuwen says. However, "In Europe we are not convinced that tamoxifen has this preventive potential." Van Leeuwen and her colleagues compared nearly 1,200 women with breast cancer, 309 of whom had also developed endometrial tumors. Of the women with uterine cancer, 36 percent had used tamoxifen, compared with 28 percent of those without the additional tumors. Risk higher with long-term use The risk of uterine cancer doubled in patients who took tamoxifen for two to five years, and spiked sevenfold among those who took it for five years or longer, the researchers found. Moreover, women on the drug were less likely to survive endometrial cancer than those who didn't use it. Tests of tumor tissue revealed that tamoxifen users had more aggressive forms of uterine cancer than women who didn't take the drug. The researchers speculate that long-term exposure to tamoxifen might promote uterine cancer in a number of ways, from acting as a form of estrogen -- which is known to prompt endometrial tumors -- to mutating DNA. "What the exact biological mechanism underlying this finding is we don't actually know," says Van Leeuwen. Dr. Richard Barakat, associate chief of gynecology at the Memorial Sloan-Kettering Cancer Center in New York City, says the Dutch research has a few crucial caveats. First, Barakat says, the study was a look-back analysis, a less conclusive investigation than randomized, controlled trials that have found no link between tamoxifen and more aggressive uterine tumors. And, Barakat says, the rate of advanced uterine cancer in the group of comparison women with the disease was only one-third of normal -- 15 to 20 percent of cases -- suggesting that they were somehow an unrepresentative population. Not surprisingly, then, he says, the rate of advanced cancers for women who took tamoxifen seemed high in comparison, though it was within the expected range. Both Barakat and Van Leeuwen say the results of a large ongoing study comparing tamoxifen and the osteoporosis drug raloxifene for breast cancer prevention should shed more light on the toxicity of these compounds. Raloxifene is believed to be less harmful to the uterus than the older drug, though its effects on other tissues are less clear. What To Do About 180,000 American women will develop breast cancer this year, and some 43,000 will die from the disease. For uterine cancer, the numbers are smaller: 32,000 cases and 6,000 deaths. Women can reduce their risk of breast cancer through lifestyle changes like regular exercise and eating a healthy diet. To learn more about breast cancer and its treatment options, visit the Karmanos Cancer Institute or the National Cancer Institute. The NCI also has information on tamoxifen. SOURCES: Interviews with Flora E. Van Leeuwen, Ph.D., epidemiologist, Netherlands Cancer Institute, Amsterdam; and Richard Barakat, M.D., associate chief of gynecology, Memorial Sloan-Kettering Cancer Center, New York; Sept. 9, 2000 The Lancet By Adam Marcus HealthSCOUT Reporter From advocate Helen Schiff 9/11/00 Breast Cancer Research & Treatment, 4/02 Cancer, 5/02 Brit J Cancer, 4/03 Remember we are NOT Doctors and have NO medical training. This site is like an Encyclopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.