Tamoxifen offers long-term benefits for breast cancer prevention among women at high risk of the disease, according to two randomized, blinded clinical trials. The trials found that the breast cancer risk reduction persists long after women stop taking tamoxifen.
Tamoxifen is used both to treat breast cancer and to prevent it among women at high risk of breast cancer. However, most of the data on tamoxifen for breast cancer prevention comes from the period when women were still taking tamoxifen, usually a period of five years. There is little information about breast cancer risk after tamoxifen use is stopped. Tamoxifen, an antiestrogen drug, is only active on estrogen receptor (ER)-positive breast cancer, which is dependent on estrogen to grow.
In the International Breast Cancer Intervention Study (IBIS-I), 7,145 women ages 35 to 70 who were at an increased risk of breast cancer were randomly assigned to receive either 20 milligrams per day of tamoxifen or a placebo for 5 years. Initial study results reported in 2002—about 4 years into the trial—showed that tamoxifen reduced the incidence of breast cancer by 32 percent. The risk reduction was only for ER-positive breast cancer; ER-negative breast cancer rates were similar in both groups.
In the updated report of the first study, Jack Cuzick, Ph.D., of the Wolfson Institute of Preventive Medicine in London, and colleagues report breast cancer rates on women about 8 years after they were enrolled in IBIS-I. Tamoxifen reduced the incidence of breast cancer by about 27 percent; this amounts to 4.97 breast cancer cases per 1,000 women in the tamoxifen group compared with 6.82 cases per 1,000 women in the placebo group. This reduction was restricted to ER-positive breast cancers. They note that, although the breast cancer reduction remained similar from the earlier report to the current one, side effects decreased after active treatment was stopped. For example, during the 5 years of tamoxifen (or placebo) treatment, women in the tamoxifen group experienced higher rates of deep-vein thrombosis and pulmonary embolism, but this difference disappeared after tamoxifen was stopped.
"These updated results from the IBIS-I trial provide further confirmation that tamoxifen reduces the risk of ER-positive breast cancers in high-risk women," the authors write. "More importantly, they provide the first randomized evidence that the benefits of tamoxifen extend beyond the active treatment period, but the side effects largely do not."
In the second study, Trevor J. Powles, Ph.D., of The Royal Marsden Hospital in London, and colleagues analyzed more than 13 years of data from 2,471 women enrolled in a clinical trial at the hospital. The women were randomly assigned to take 20 mg/day of tamoxifen or a placebo daily for 8 years. In their initial analysis in 1998, the researchers reported that there was no difference in breast cancer rates between the two groups, when using about 6 years of follow-up data.
In the new analysis with a 20 year follow-up, the researchers again found that overall invasive breast cancer rates were not statistically different (82 breast cancer cases among 1,238 women on tamoxifen, and 104 cases among 1,233 women on placebo). However, when the researchers looked specifically at ER-positive breast cancers, they found that tamoxifen reduced the risk of ER-positive breast cancer by 39 percent. This reduction occurred for the most part in the later follow-up period.
"We found that...a highly statistically significant risk reduction was found that could be attributed principally to a reduction in the risk of ER-positive breast cancers," the authors write. "This reduced risk appears to be increasing with longer follow-up."
In an editorial, Umberto Veronesi, M.D., of the European Institute of Oncology in Milan, Italy, and colleagues put the new results in context with other long-term studies of tamoxifen for breast cancer prevention. They note that, because both trials find that tamoxifen reduced the risk of only ER-positive cancers, it's important to identify specific risk factors for these cancers so tamoxifen use can be appropriately guided. "The results of these two trials ... convincingly move tamoxifen beyond the proof-of-principle stage and underscore its worth as a viable standard option for preventing ER-positive breast cancer in high-risk women," the editorialists write.