Based on a thorough review of all the available data, the FDA approved tamoxifen for the reduction of breast cancer incidence in high-risk pre- and postmenopausal women in 1998. However, the report that tamoxifen caused a small but significant increase in uterine sarcoma209 resulted in an industry request for a black box inclusion for tamoxifen from the FDA. Additionally, the IBIS-1 study noted an unacceptable increase in deaths from tamoxifen treated patients who inadvertently had surgery during the study acceptability of tamoxifen as a chemopreventive.210 This led to the development of IBIS-2 using an aromatase inhibitor to prevent breast cancer. Aromatase inhibitors have fewer side effects than tamoxifen and it is known that during adjuvant treatment, they reduce the incidence of contralateral breast cancer even more than tamoxifen.211-213
Another approach is the evaluation of the SERM raloxifene as a preventive for breast cancer in high-risk postmenopausal women. The Study of Tamoxifen and Raloxifene (STAR) has reduced its recruitment goal of 19 000 volunteers and the results will be available by July 2006.
The promise of the chemoprevention for breast cancer is becoming a reality. However, there are many challenges. Tamoxifen, the pioneering medicine, is considered by many to be too controversial to be widely used as a chemopreventive. However, there are no alternatives for the premenopausal woman at high risk for breast cancer and the good news is that this risk group has the best risk-benefit ratio.214 For postmenopausal women, where the side effects are well defined, the future depends on the results of current clinical trials with raloxifene or aromatase inhibitors. Unfortunately, there are no comparisons of a SERM with an aromatase inhibitor so the choice of a chemopreventive strategy will need to be made on a patient-by-patient basis. In other words, the options are the use of raloxifene or an aromatase inhibitor with bone monitoring and a bisphosphonate to avoid osteoporosis.
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