Dahabreh Issa, Terasawa Teruhiko, Castaldi Peter, Trikalinos Thomas A
ICRHPS, Tufts Medical Center; Department of Internal Medicine, Fujita Health University School of Medicine; Tufts Medical Center and Tufts Evidence-based Practice Center, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center.
PLoS Curr. 2010 Sep 2;2:RRN1176. doi: 10.1371/currents.RRN1176.
Tamoxifen, a selective estrogen receptor modulator, is the standard of care for premenopausal women with estrogen or progesterone receptor-positive breast cancer and a valid option for treating post-menopausal women. However, a substantial number of tamoxifen-treated patients relapse following surgical resection, while others remain disease-free for many years. It appears that the primary effectors of tamoxifen activity are its active metabolites, rather than tamoxifen itself. Cytochrome P450 (CYP) enzymes, CYP2D6 in particular, play a major role in the metabolism of tamoxifen to active metabolites. More than 75 germline CYP2D6 variants have been identified. A test predicting lack of response to tamoxifen could supplement information used by clinicians and patients in treatment decision-making. For example, physicians and patients may opt to switch to an alternative therapy upfront.
他莫昔芬是一种选择性雌激素受体调节剂，是雌激素或孕激素受体阳性的绝经前乳腺癌女性的标准治疗药物，也是治疗绝经后女性的有效选择。然而，相当数量接受他莫昔芬治疗的患者在手术切除后复发，而其他患者则多年无病生存。他莫昔芬活性的主要效应物似乎是其活性代谢产物，而非他莫昔芬本身。细胞色素P450（CYP）酶，尤其是CYP2D6，在他莫昔芬代谢为活性代谢产物的过程中起主要作用。已鉴定出75种以上的CYP2D6种系变体。一种预测对他莫昔芬无反应的检测方法可以补充临床医生和患者在治疗决策中使用的信息。例如，医生和患者可能会选择提前改用替代疗法。
