Sim Sarah, Lövrot John, Lindh Jonatan D, Bergh Jonas, Xie Hanjing
Department of Physiology & Pharmacology, Karolinska Institutet, SE171-76 Stockholm, Sweden.
Department of Oncology & Pathology, Karolinska Institutet, SE171-76 Stockholm, Sweden.
Pharmacogenomics. 2018 Aug 1;19(13):1027-1037. doi: 10.2217/pgs-2018-0089. Epub 2018 Jul 19.
We investigated the interaction of CYP2C19 and CYP2D6 genotype on clinical outcome in tamoxifen-treated breast cancer patients.
MATERIALS & METHODS: A cohort of 306 patients on tamoxifen treatment for a minimum of 1 year were employed to analyze the effect of genotype-predicted phenotype on relapse-free survival.
RESULTS & CONCLUSION: We show that the group with worst outcome and highest risk of relapse is that of 2C19↑-2D6↓ (hazard ratio: 2.94), when adjusting for age, Nottingham prognostic index and adjuvant chemotherapy. Furthermore, the effect of 2C19↑-2D6↓genotype-predicted phenotype is greatly enhanced in premenopausal patients (hazard ratio: 21.08). We hypothesize that poor bioactivation of tamoxifen in patients with low CYP2D6 activity and high CYP2C19 metabolism represents a tamoxifen-treated patient group that has the worst clinical outcome.
我们研究了CYP2C19和CYP2D6基因分型对他莫昔芬治疗的乳腺癌患者临床结局的相互作用。
选取306例接受他莫昔芬治疗至少1年的患者队列，分析基因分型预测表型对无复发生存率的影响。
我们发现，在调整年龄、诺丁汉预后指数和辅助化疗后，结局最差且复发风险最高的组是CYP2C19活性增强-CYP2D6活性降低组（风险比：2.94）。此外，CYP2C19活性增强-CYP2D6活性降低基因分型预测表型在绝经前患者中的影响显著增强（风险比：21.08）。我们推测，CYP2D6活性低且CYP2C19代谢高的患者中他莫昔芬的生物活化不良代表了临床结局最差的他莫昔芬治疗患者组。
