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matase is a cytochrome P-450 enzyme that catalyzes the rate-limiting step in the synthesis of estradiol from androgens.72 The aromatase inhibitors represent a new class of agents in the treatment and prevention of breast cancer. Recent evidence suggests that aromatase inhibitors have several advantages over tamoxifen for the prevention and treatment of breast cancer.73-75 For example, aromatase inhibitors are effective in treating tamoxifen-resistant cancers as second-line agents, and they do not increase the risk of endometrial cancers.76 It is likely that the aromatase inhibitors may replace tamoxifen in the management of metastatic breast cancer.77 However, there is concern that these estrogen-lowering drugs may promote osteoporosis or decrease bone density and, in turn, increase the risk of bone fractures. Because aromatase inhibitors cannot prevent the production of estrogen by the ovaries, the use of aromatase inhibitors may be limited to postmenopausal women.

Another potential alternative to tamoxifen that prevents bone loss and does not appear to increase the risk of endome-trial cancer is raloxifene.78 Results from the Multiple Outcomes of Raloxifene Evaluation Trial showed that raloxifene has positive estrogenic effects on bone and lipid metabolism and antiestrogenic effects on breast tissue.78 Even though this trial was designed to assess raloxifene's effect on bone density, results showed a 65% reduction in risk of both in situ and invasive breast cancer in women taking raloxifene78; moreover, raloxifene did not appear to increase risk of endometrial cancer. These results have led to further evaluation of ralox-ifene as a possible alternative to tamoxifen. Currently, raloxifene is being evaluated in the Study of Tamoxifen and Raloxifene (STAR) trial.65

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