Brodie A M, Njar V C
Department of Pharmacology and Experimental Therapeutics, School of Medicine, University of Maryland, Baltimore 21201, USA.
Semin Oncol. 1996 Aug;23(4 Suppl 9):10-20.
Selective aromatase inhibitors cause regression of breast carcinomas by reducing estrogen production via inhibition of the enzyme aromatase (estrogen synthetase). A higher incidence of hormone-dependent breast cancer occurs in postmenopausal women than in younger women. Thus, total estrogen blockade is more likely to be achieved with systemic (pharmacologic) methods than by surgical removal of endocrine glands. At the present time, breast cancer patients with hormone-dependent disease usually receive the antiestrogen tamoxifen as first-line treatment. Although tamoxifen is effective initially, patients develop resistance to the drug, which results in disease progression. Aromatase inhibitors acting by a different mechanism from tamoxifen are effective in some of these patients. There is also the potential that aromatase inhibitors could be more effective as first-line treatment. Formestane, 4-hydroxyandrostenedione, the first approved aromatase inhibitor, is proving to be useful in postmenopausal breast cancer patients with advanced disease. Recently, anastrozole, a nonsteroidal agent, has been approved in the United States. Other very potent aromatase inhibitors are under development. Aromatase inhibitors as a new class of well-tolerated agents are now becoming available for improving the treatment of breast cancer patients.
选择性芳香化酶抑制剂通过抑制芳香化酶（雌激素合成酶）来减少雌激素生成，从而使乳腺癌消退。绝经后女性激素依赖性乳腺癌的发病率高于年轻女性。因此，与通过手术切除内分泌腺相比，采用全身（药物）方法更有可能实现完全的雌激素阻断。目前，激素依赖性疾病的乳腺癌患者通常接受抗雌激素他莫昔芬作为一线治疗。虽然他莫昔芬最初有效，但患者会对该药物产生耐药性，从而导致疾病进展。作用机制与他莫昔芬不同的芳香化酶抑制剂在部分此类患者中有效。芳香化酶抑制剂作为一线治疗可能也更有效。福美司坦，即首个获批的芳香化酶抑制剂4-羟基雄烯二酮，已被证明对患有晚期疾病的绝经后乳腺癌患者有用。最近，非甾体类药物阿那曲唑在美国已获批。其他非常强效的芳香化酶抑制剂也在研发中。作为一类耐受性良好的新型药物，芳香化酶抑制剂现正逐渐用于改善乳腺癌患者的治疗。
