Department of Oncology, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905, USA.
J Clin Oncol. 2010 Jun 1;28(16):2768-76. doi: 10.1200/JCO.2009.23.8931. Epub 2010 May 3.
Evidence has emerged that the clinical benefit of tamoxifen is related to the functional status of the hepatic metabolizing enzyme cytochrome P450 2D6 (CYP2D6). CYP2D6 is the key enzyme responsible for the generation of the potent tamoxifen metabolite, endoxifen. Multiple studies have examined the relationship of CYP2D6 status to breast cancer outcomes in tamoxifen-treated women; the majority of studies demonstrated that women with impaired CYP2D6 metabolism have lower endoxifen concentrations and a greater risk of breast cancer recurrence. As a result, practitioners must be aware that some of the most commonly prescribed medications coadministered with tamoxifen interfere with CYP2D6 function, thereby reducing endoxifen concentrations and potentially increasing the risk of breast cancer recurrence. After reviewing the published data regarding tamoxifen metabolism and the evidence relating CYP2D6 status to breast cancer outcomes in tamoxifen-treated patients, we are providing a guide for the use of medications that inhibit CYP2D6 in patients administered tamoxifen.
有证据表明，他莫昔芬的临床获益与肝代谢酶细胞色素 P450 2D6（CYP2D6）的功能状态有关。CYP2D6 是生成强效他莫昔芬代谢物，依西美坦的关键酶。多项研究探讨了 CYP2D6 状态与接受他莫昔芬治疗的女性乳腺癌结局之间的关系；大多数研究表明，CYP2D6 代谢受损的女性依西美坦浓度较低，乳腺癌复发风险较高。因此，临床医生必须意识到，一些最常开的与他莫昔芬联合使用的药物会干扰 CYP2D6 的功能，从而降低依西美坦的浓度，并可能增加乳腺癌复发的风险。在回顾了关于他莫昔芬代谢的已发表数据以及 CYP2D6 状态与接受他莫昔芬治疗的患者乳腺癌结局之间的关系后，我们为接受他莫昔芬治疗的患者中抑制 CYP2D6 的药物的使用提供了指南。
