Friedrichs K, Jänicke F
Frauenklinik und Poliklinik, Universitäts-Krankenhaus Eppendorf, Hamburg.
Praxis (Bern 1994). 1998 Apr 22;87(17):584-8.
Aromatase inhibition is now an acknowledged second line treatment modality for advanced breast cancer in postmenopausal women. Aminoglutethimide is an inhibitor of adrenal steroid biosynthesis and blocks the conversion of cholesterol to pregnenolone, and therefore reduces levels of adrenal androgens, which are a source of estrogens in both premenopausal and postmenopausal women. Aminoglutethimide has produced antitumor response rates of 35% in unselected patients, most of whom have undergone prior therapy with either chemotherapy or hormonal manipulation. As is true of other hormonal responses, high response rates of up to 70% are observed in patients who are ER and/or PR positive. The reason why these drugs are currently used after tamoxifen is mainly due to the side effects of aminoglutethimide, which impairs the mineralocorticoid and glucocorticoid synthesis. New, less toxic compounds appear, which block the conversion of androstenedione to estrone and efficiently suppress plasma estrogen levels., e.g. formestane, anastrozole and letrozole. Aromatase inhibitors are now being compared to tamoxifen as first-line endocrine treatment in relapsing patients. If these trials confirm a similar or better response rate to new aromatase inhibitors compared to tamoxifen, the time will come to study them as the first line adjuvant treatment in non-metastatic disease.
芳香化酶抑制作用目前是绝经后妇女晚期乳腺癌公认的二线治疗方式。氨鲁米特是肾上腺类固醇生物合成的抑制剂，可阻断胆固醇转化为孕烯醇酮，从而降低肾上腺雄激素水平，而肾上腺雄激素是绝经前和绝经后妇女雌激素的来源之一。在未经过筛选的患者中，氨鲁米特产生的抗肿瘤反应率为35%，其中大多数患者之前已接受过化疗或激素治疗。与其他激素反应情况相同，雌激素受体（ER）和/或孕激素受体（PR）阳性的患者中观察到高达70%的高反应率。目前这些药物在他莫昔芬之后使用的原因主要是氨鲁米特的副作用，它会损害盐皮质激素和糖皮质激素的合成。出现了毒性较小的新化合物，它们可阻断雄烯二酮转化为雌酮，并有效抑制血浆雌激素水平，例如福美司坦、阿那曲唑和来曲唑。目前正在将芳香化酶抑制剂与他莫昔芬作为复发性患者的一线内分泌治疗进行比较。如果这些试验证实新的芳香化酶抑制剂与他莫昔芬相比有相似或更好的反应率，那么就到了将它们作为非转移性疾病的一线辅助治疗进行研究的时候了。
