Data from additional years of follow-up of a large randomized placebo-controlled clinical trial of tamoxifen for the prevention of breast cancer confirm that the drug reduces the risk of invasive and noninvasive breast cancer, according to a report that appears in the current issue of the Journal of the National Cancer Institute.
The National Surgical Adjuvant Breast and Bowel Project (NSABP) Breast Cancer Prevention Trial (P-1) began in 1992. More than 13,000 women aged 35 years and older who were at high risk for breast cancer were randomly assigned to receive either a placebo or tamoxifen for 5 years. In 1998, the study's independent data monitoring committee recommended that the study be unblinded. An overall 49% reduction in breast cancer risk was observed in women taking tamoxifen. Participants were informed of whether they were taking a placebo or tamoxifen so that women who were taking placebo could be given the option to take tamoxifen.
The initial findings from the study--which appeared in the Sept. 16, 1998, issue of the Journal of the National Cancer Institute--indicated that tamoxifen reduced the risk of invasive and noninvasive breast cancer. Tamoxifen was also found to reduce the risk of osteoporotic fractures but to increase the risks of endometrial cancer and thromboembolism.
In their follow up study, Bernard Fisher, M.D., and colleagues have updated the P 1 data. They found that, after 7 years of follow-up, the cumulative rate of invasive breast cancer was reduced by 43%, from 42.5 cases per 1,000 women in the placebo group to 24.8 cases per 1,000 women in the tamoxifen group. The rate of noninvasive breast cancer was reduced by 37%, from 15.8 cases per 1,000 women in the placebo group to 10.2 cases per 1,000 women in the tamoxifen group. The risks of stroke, deep-vein thrombosis, cataracts, ischemic heart disease, and death were similar to what was reported in 1998. The risk of pulmonary embolism was about 11% lower and the risk of endometrial cancer was about 29% higher than first reported, but these differences were not statistically significant. The net benefit of tamoxifen varied by age, race, and level of breast cancer risk. The authors conclude that cohorts of women at increased risk for breast cancer who could derive a net benefit from receiving tamoxifen have been clearly identified.
"The P-1 trial should … be viewed as the starting point from which a new paradigm for breast cancer management can evolve. In that regard, a series of new breast cancer prevention trials are currently being conducted in postmenopausal women to evaluate other agents that could be more effective than tamoxifen in decreasing risk of breast tumors and reducing the frequency of undesirable side effects noted with the drug," the authors write. However, they note, "until one of these trials demonstrates a greater net benefit from an alternative therapy, tamoxifen remains the only proven chemopreventive treatment for breast cancer risk reduction."