|
Tamoxifen and chemopreventive treatment for breast cancer risk reduction
In 1992, the National Surgical Adjuvant Breast and Bowel Project (NSABP) began the Breast Cancer Prevention Trial (P-1), a double-blinded, randomized clinical trial designed to determine whether tamoxifen could prevent breast cancer in women at high risk for the disease. In that study, more than 13,000 women aged 35 years and older were randomly assigned to either tamoxifen or placebo for 5 years. Initial findings from P-1, which were reported in 1998, when the trial was unblinded, demonstrated a reduction in the risk of both invasive and noninvasive estrogen receptor-positive breast cancer in women who received tamoxifen. Tamoxifen also reduced the risk of osteoporotic fractures but increased the risks of endometrial cancer and thromboembolism. In the updated report of the P-1 study, after 7 years of follow-up, it was found that tamoxifen continued to substantially reduce the cumulative rates of invasive and noninvasive breast cancer and to significantly reduce the rate of osteoporotic fractures. These reductions were similar to those observed in the original report of P-1. Risks of pulmonary embolism were lower than in the original report, and risks of endometrial cancer were higher. The net benefit from tamoxifen varied by age, race, and level of breast cancer risk. The authors of the updated report clearly identified cohorts of women at increased risk for breast cancer. It has been estimated that approximately 2.5 million women in the United States could derive a net benefit from tamoxifen. The P-1 trial should be viewed not only as the first study that demonstrated that breast cancer can be prevented but also 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 the risk of breast cancer and reducing the frequency of undesirable side effects noted with the drug. However, 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.
Reference:
Bernard Fisher Operations Center, National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, USA
|