Aromatase inhibitors: are there differences between steroidal and nonsteroidal aromatase inhibitors and do they matter?
Aromatase inhibitors: are there differences between steroidal and nonsteroidal aromatase inhibitors and do they matter?
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DOI：
10.1634/theoncologist.2008-0055
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发表时间：
2008-08
期刊：
影响因子：
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通讯作者：
W. Miller;J. Bartlett;A. Brodie;R. Brueggemeier;E. di Salle;P. Lønning;A. Llombart;N. Maass;T. Maudelonde;H. Sasano;P. Goss
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文献类型：
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作者：
W. Miller;J. Bartlett;A. Brodie;R. Brueggemeier;E. di Salle;P. Lønning;A. Llombart;N. Maass;T. Maudelonde;H. Sasano;P. Goss
芳香酶抑制剂（AI）被批准用于绝经后妇女的早期和晚期乳腺癌。尽管目前批准的“第三代”AI均能有效抑制雌激素合成，但它们可细分为类固醇和非类固醇抑制剂，它们与芳香酶的相互作用不同。非类固醇 AI 以非共价且可逆的方式与芳香酶蛋白结合，而类固醇 AI 可以以共价且不可逆的方式与芳香酶结合。类固醇 AI 依西美坦可能会产生雄激素作用，但其临床相关性尚未确定。类固醇和非类固醇 AI 之间的转换会产生一定程度的额外临床益处，表明各类抑制剂之间存在部分非交叉耐药性。在这种情况下，对第二次人工智能的回应率普遍较低；关于人工智能的最佳序列还需要进一步的研究。迄今为止，临床研究表明，雌激素受体阻滞剂与非类固醇 AI 联合使用并不能提高疗效，而与类固醇 AI 联合使用尚未得到评估。比较类固醇和非类固醇 AI 的头对头试验结果将确定不同类 AI 之间在疗效或不良事件方面是否存在有意义的临床差异。本综述总结了有关已知差异的现有证据，并评估了其潜在的临床影响。
Aromatase inhibitors (AIs) are approved for use in both early- and advanced-stage breast cancer in postmenopausal women. Although the currently approved "third-generation" AIs all powerfully inhibit estrogen synthesis, they may be subdivided into steroidal and nonsteroidal inhibitors, which interact with the aromatase enzyme differently. Nonsteroidal AIs bind noncovalently and reversibly to the aromatase protein, whereas steroidal AIs may bind covalently and irreversibly to the aromatase enzyme. The steroidal AI exemestane may exert androgenic effects, but the clinical relevance of this has yet to be determined. Switching between steroidal and nonsteroidal AIs produces modest additional clinical benefits, suggesting partial noncrossresistance between the classes of inhibitor. In these circumstances, the response rates to the second AI have generally been low; additional research is needed regarding the optimal sequence of AIs. To date, clinical studies suggest that combining an estrogen-receptor blocker with a nonsteroidal AI does not improve efficacy, while combination with a steroidal AI has not been evaluated. Results from head-to-head trials comparing steroidal and nonsteroidal AIs will determine whether meaningful clinical differences in efficacy or adverse events exist between the classes of AI. This review summarizes the available evidence regarding known differences and evaluates their potential clinical impact.