Women randomized to 5 years of tamoxifen in the overview analysis were found to have a 47% (SD 9) reduction in the risk of contralateral breast cancer. In light of these promising results, large-scale trials were initiated in Europe and North America to definitively evaluate tamoxifen as a chemopreventive agent in healthy high-risk women.
The National Surgical Adjuvant Breast and Bowel Project (NSABP) has recently reported results from the Breast Cancer Prevention Trial (BCPT), a randomized double-blind, placebo-controlled trial of tamoxifen involving 13,388 high-risk women. Women were eligible for this trial if they were over the age of 60, or if their risk of breast cancer was calculated to be that of a 60-year-old woman (equivalent to a risk of breast cancer of 1.67 % over 5 years).
For women under age 60, the modified Gail model calculated this risk. This model took into account several risk factors including number of first-degree relatives with breast cancer, current age of the participant, age at menarche and at time of first delivery, parity, number of breast biopsies and history of atypical hyperplasia. Women with a history of lobular carcinoma in situ were eligible based on their risk of breast cancer after this biopsy result alone.
After a median follow-up of 4.5 years, a 49% reduction in the risk of invasive breast cancer was observed among the participants randomized to tamoxifen, with a relative risk of 0.51 (range, 0.39-0.66). This number closely approximates the risk reduction in the overview analysis, supporting the benefits of tamoxifen as a chemopreventive agent.
In addition, there was a significant reduction in the risk of noninvasive breast cancer, including ductal carcinoma in situ. Tamoxifen was also shown to reduce the number of fractures in the hip, wrist and spine; however, there was no difference in the risk of ischemic cardiac events between the treatment groups. As expected, there was an increased risk of thromboembolic events, including pulmonary emboli and deep vein thromboses in the tamoxifen group, with a relative risk of 3.01 (range, 1.15-9.27) and 1.60 (range, 0.91-2.86), respectively.
The results of two European studies evaluating tamoxifen as a chemopreventive agent have failed to confirm the positive results that were reported by the NSABP. These European trials differed from the NSABP trial with respect to trial design, size and populations of women enrolled, such that a valid comparison between the three trials is difficult to perform.
In addition, these trials allowed the use of hormone replacement therapy, which may have confounded the results. The negative European trials remain blinded, and will be updated after follow-up analyses.
Maura N. Dickler
American Cancer Society Guidelines for the Early Detection of Breast Cancer: Update 2003. CA Cancer J Clin 2003
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