Gaston Cindy, Kolesar Jill
University of Wisconsin Hospitals and Clinics, Madison, WI 53792, USA.
Clin Adv Hematol Oncol. 2008 Nov;6(11):825-33.
Tamoxifen has been used as adjuvant hormonal therapy for estrogen receptor positive breast cancer for over 30 years and is also widely used for the treatment of metastatic breast cancer. Tamoxifen is metabolized to its more active form by cytochrome P450 2D6 (CYP2D6); decreases in CYP2D6 activity, either by inactivating polymorphisms or drug interactions, can reduce concentrations of tamoxifen's active metabolites. Clinical studies demonstrate that breast cancer patients treated with adjuvant tamoxifen who have decreased CYP2D6 due to genetic polymorphisms or drug interactions may have an increased risk of recurrence and reductions in disease-free survival. Pharmacogenetic testing is currently available to predict CYP2D6 phenotypes and individualize tamoxifen therapy.
他莫昔芬作为雌激素受体阳性乳腺癌的辅助激素治疗药物已使用了30多年，也广泛用于转移性乳腺癌的治疗。他莫昔芬通过细胞色素P450 2D6（CYP2D6）代谢为活性更高的形式；CYP2D6活性的降低，无论是由于失活的基因多态性还是药物相互作用，都可能降低他莫昔芬活性代谢物的浓度。临床研究表明，因基因多态性或药物相互作用导致CYP2D6降低而接受辅助性他莫昔芬治疗的乳腺癌患者，复发风险可能增加，无病生存期缩短。目前可进行药物遗传学检测以预测CYP2D6表型并实现他莫昔芬治疗的个体化。
