More Evidence That Tamoxifen Prevents Breast Cancer In High-Risk Women (dateline September 14, 2002)
Preliminary results of a large European clinical trial find that the drug tamoxifen (brand name, Nolvadex) reduces the risk of breast cancer by one-third among women at high risk of the disease. The trial results are consistent with findings from a large U.S. clinical trial, although the amount of the risk reduction was found to be slightly lower in the European trial (30% reduced risk of breast cancer with tamoxifen versus 49% in the U.S. trial). However, the lead researcher of the European trial warned that these trial results do not suggest that the benefits of tamoxifen outweigh the risks for healthy women at high breast cancer risk. The trial found the increased risk of blood clots to be the most serious potential side effect of tamoxifen.
Tamoxifen is an anti-estrogen drug commonly used to treat estrogen-sensitive breast cancer, usually in conjunction with surgery and/or other treatments. Recently, a clinical trial conducted by researchers of the University of Pittsburgh's National Adjuvant Breast and Bowel Project (NSABP) found that tamoxifen reduced the risk of breast cancer in high risk women by nearly 50%, compared to women who took a placebo (an inactive pill). In fact, the trial was stopped early so that the women taking the placebo could also benefit from tamoxifen. However, British researchers argued that more long-term studies were needed to determine whether the benefits of tamoxifen were greater than its risks.
Therefore, European researchers began the International Breast Cancer Intervention Study (IBIS), which involved more than 7,000 healthy, high-risk women from the United Kingdom, Finland, Switzerland, Belgium, Australia, and New Zealand. Like the U.S. NSABP trial, half of the women in the study were given tamoxifen and half a placebo.
In March 2002 at the 3rd European Breast Cancer Conference in Barcelona, Spain, Professor Jack Cuzick from Cancer Research U.K. presented early results of the IBIS trial. He also presented a review of other breast cancer prevention trials: the NSABP P1 Tamoxifen Prevention Trial, the Royal Marsden Hospital Chemoprevention Trial, and the Italian National Trial. In the IBIS trial, Professor Cuzick said that tamoxifen reduced the risk of breast cancer by one-third in high risk women, compared to the women taking a placebo.
While Professor Cuzick said that the benefits of tamoxifen were "indisputable," he also cautioned that there is no conclusive evidence that those benefits outweigh the risks for healthy, high-risk women (Cuzick said that the benefits do generally outweigh the risks when tamoxifen is taken as a treatment for women already diagnosed with breast cancer). In the IBIS trial, Professor Cuzick noted a two to three times higher risk of endometrial cancer (cancer of the uterine lining) and thromboembolism (the blocking of a blood vessel by a blood clot dislodged from its original site).
"Every effort should be made to reduce this risk [of thromboembolism], although we must keep it in perspective," said Professor Cuzick, as published in a Federation of European Cancer Societies press release on the IBIS trial. "It is about the same level of risk as that faced by a woman taking HRT [hormone replacement therapy], and if you are a breast cancer patient taking tamoxifen for treatment it is absolutely essential that you continue the treatment. Tamoxifen is a lifesaver and the single most effective medical treatment for breast cancer. Any risks from tamoxifen used for treatment are far outweighed by the benefits. There are many more thousands of breast cancer patients alive today because of tamoxifen."
While the rate of non-breast cancer deaths in the IBIS trial were general similar among the women who took tamoxifen and the women who took a placebo, there was a slight increase in the deaths from thromboembolism, suggesting that these blood clots are the most serious potential complication of tamoxifen. Deaths from thromboembolism were also higher in one other trial that Professor Cuzick reviewed. Of the blood clotting cases among tamoxifen users, 40% occurred within three months of surgery or after a patient was immobile for a prolonged period of time. Thus, Professor Cuzick said healthy patients should be advised to discontinue tamoxifen prior to any major surgery and not to re-start tamoxifen for at least one month following surgery. Patients who become immobile should follow similar precautions, said Professor Cuzick. Overall, Cuzick and his team calculated that preventive tamoxifen could reduce breast cancer deaths by 18%.
According to the IBIS trial, the NSABP trial, and other results, tamoxifen is only effective at preventing or treating estrogen-sensitive, or estrogen receptor-positive, breast cancer (i.e., cancer that contains estrogen receptors and depends on the hormone for survival). Approximately 80% of breast cancer cases are estrogen receptor-positive and the remaining 20% are estrogen receptor-negative (i.e., do not depend on estrogen for survival).