Tamoxifen offers long-term benefits for breast cancer prevention among women at high risk of the disease, according to two randomized, blinded clinical trials in the February 21 Journal of the National Cancer Institute. 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."