Lønning P E
Department of Oncology, Haukeland University Hospital, Bergen, Norway.
Acta Oncol. 1996;35 Suppl 5:38-43. doi: 10.3109/02841869609083966.
While the first generation aromatase inhibitor aminoglutethimide and second- and third generation inhibitors like formestane and fadrozole all have been found to inhibit in vivo aromatization by 85-93%, the novel aromatase inhibitors letrozole and arimidex inhibit in vivo aromatization by 97-99%. However, we do not know whether these drugs cause a higher response rate or a longer duration of remission compared with less potent aromatase inhibitors. Lack of cross-resistance to steroidal and non-steroidal aromatase inhibitors suggests that these drugs may have partially different mechanisms of action, probably by influencing the intratumour aromatase enzyme. Recent studies have shown that breast cancer cells may adapt to alterations in oestrogen concentration in vitro by increasing their sensitivity. The observation that patients suffering relapse following castration, hypophysectomy or adrenalectomy may respond to treatment with aromatase inhibitors suggests that similar mechanisms could be responsible for acquired resistance to oestrogen deprivation.
虽然第一代芳香化酶抑制剂氨鲁米特以及第二代和第三代抑制剂如福美司坦和法倔唑均已被发现可在体内抑制85%-93%的芳香化作用，但新型芳香化酶抑制剂来曲唑和阿那曲唑在体内可抑制97%-99%的芳香化作用。然而，与效力较弱的芳香化酶抑制剂相比，我们并不清楚这些药物是否能带来更高的缓解率或更长的缓解持续时间。对甾体类和非甾体类芳香化酶抑制剂不存在交叉耐药性表明，这些药物可能具有部分不同的作用机制，可能是通过影响肿瘤内的芳香化酶来实现的。最近的研究表明，乳腺癌细胞在体外可能通过提高敏感性来适应雌激素浓度的变化。去势、垂体切除或肾上腺切除术后复发的患者可能对芳香化酶抑制剂治疗有反应，这一观察结果表明，类似的机制可能导致对雌激素剥夺产生获得性耐药。
