Tamoxifen still is the mainstay of endocrine therapy in women with advanced breast cancer. Response rates in hormone receptor-positive patients are reported in about 50%. Second-line therapy so far consisted of high-dosed progestins such as megestrolacetate or of the first-generation aromatase inhibitor aminoglutethimide. Though the objective remission rates still are about 25–30%, these drugs have a considerable side effect potential. The first selective aromatase inhibitor introduced was the steroid aromatase inhibitor 4-hydroxyandrostenedione (4-OHA). Due to a high first-pass effect, 4-OHA has to be applicated parenterally. The higher selectivity leads to a better tolerability. In a next step, highly selective, orally applicable aromatase inhibitors were developed. These third-generation aromatase inhibitors such as letrozole, anastrozole or vorozole combine high remission rates and low side effect potential with the possibility of oral daily application. In phase II and III studies these new aromatase inhibitors could show their superiority over progestins. Letrozole and vorozole even achieved higher remission rates than aminoglutethimide. Therefore the third-generation aromatase inhibitors should be used in the second-line therapy of advanced breast cancer after failure of tamoxifen. Trials are in progress to test the use of the new aromatase inhibitors in the adjuvant or first-line therapy.

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1999
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