Stearns Vered, Rae James M
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21231-1000, USA.
Expert Rev Mol Med. 2008 Nov 20;10:e34. doi: 10.1017/S1462399408000896.
The identification of genetic polymorphisms that influence the efficacy and safety of therapies for breast cancer may allow future treatments to be individualised based not only on tumour characteristics but also on host genetics. Genetic factors that affect the metabolism, efficacy and safety of tamoxifen, one of the most common drugs used for the treatment and prevention of breast cancer, have received particular attention. Cytochrome P450 2D6 (CYP2D6) is crucial in the metabolism of tamoxifen to its active metabolite endoxifen. Women with genetic variants of CYP2D6 or who take drugs that inhibit the enzyme have low endoxifen plasma concentrations and may show reduced benefits to tamoxifen treatment. CYP2D6 polymorphisms and variants in other candidate genes may also influence secondary benefits and side effects of tamoxifen. Here, we summarise data suggesting that CYP2D6 status may be an important predictor of the benefits of tamoxifen to an individual; in addition, we briefly discuss the role of variants in other candidate genes. Whether CYP2D6 status should be determined prior to initiating tamoxifen therapy is currently under debate and may be appropriate only for select women who are candidates for tamoxifen alone but for whom alternative standard options are available.
识别影响乳腺癌治疗疗效和安全性的基因多态性，可能使未来的治疗不仅基于肿瘤特征，还基于宿主遗传学进行个体化。他莫昔芬是治疗和预防乳腺癌最常用的药物之一，影响其代谢、疗效和安全性的遗传因素受到了特别关注。细胞色素P450 2D6（CYP2D6）在他莫昔芬代谢为其活性代谢物4-羟基他莫昔芬的过程中起关键作用。携带CYP2D6基因变异或服用抑制该酶药物的女性，其血浆中4-羟基他莫昔芬浓度较低，他莫昔芬治疗的获益可能降低。CYP2D6基因多态性及其他候选基因的变异也可能影响他莫昔芬的次要获益和副作用。在此，我们总结数据表明，CYP2D6状态可能是他莫昔芬对个体获益的重要预测指标；此外，我们简要讨论其他候选基因变异的作用。在开始他莫昔芬治疗前是否应确定CYP2D6状态目前仍在争论中，可能仅适用于仅适合他莫昔芬治疗但有其他标准替代方案的特定女性。
