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目的:研究乳腺癌术后服用他莫昔芬(TAM)辅助治疗绝经前、雌激素受体(ER)阳性患者CYP2D6基因多态性与TAM活性代谢产物Endoxifen血药浓度的相关性,及其与TAM不良反应发生的相关性。方法:57例乳腺癌术后经TAM辅助治疗的患者(绝经前、ER阳性),采用Tetra-primer ARMS PCR检测其CYP2D6基因型,采用LC-MS/MS测定所有患者体内TAM及其活性代谢产物Endoxifen的血药浓度;根据患者自述标记存在治疗不良反应的个体。结果:CYP2D6*10/*10型和*1/*10型受试者体内Endoxifen的血药浓度值分别为(23.55±4.01)和(25.90±3.93)ng/mL,均显著低于*1/*1型受试者(34.82±5.95)ng/mL,差异有统计学意义,P<0.01;但*10/*10型和*1/*10型之间Endoxifen的浓度值差异无统计学意义,P>0.05。CYP2D6*1/*1型组自述无任何不良反应的比例(22.2%)低于突变组(62.5%),且差异有统计学意义,P<0.05。结论:CYP2D6基因多态性与Endoxifen血药浓度的差异及TAM治疗不良反应的发生有关;根据CYP2D6基因型,可指导绝经前、ER阳性乳腺癌患者术后的TAM个体化用药。
Objective: To study the correlation between CYP2D6 polymorphism and endotoxemic plasma concentration of TAM, adjuvant to tamoxifen (TAM) in premenopausal and estrogen receptor (ER) positive patients after breast cancer surgery. TAM adverse reactions occurred in the correlation. Methods: 57 TAM-assisted patients (premenopausal and ER positive) after breast cancer surgery were enrolled in this study. CYP2D6 genotypes were detected by Tetra-primer ARMS PCR. TAM and its active metabolites in all patients were determined by LC-MS / MS Endoxifen blood concentration; according to patient readme mark the existence of adverse reactions in the treatment of individuals. Results: The plasma concentrations of Endoxifen in CYP2D6 * 10 / * 10 and * 1 / * 10 subjects were (23.55 ± 4.01) and (25.90 ± 3.93) ng / mL, * 1 type (34.82 ± 5.95) ng / mL, the difference was statistically significant, P <0.01; however, there was no significant difference in endoxifen concentration between * 10 / * 10 and * 1 / * 10 , P> 0.05. The proportion of self-reported CYP2D6 * 1 / * 1 group without any adverse reactions was lower than that of the mutation group (62.2%) (22.2%), and the difference was statistically significant (P <0.05). Conclusion: The difference of CYP2D6 gene polymorphism and Endoxifen plasma concentration is related to the occurrence of adverse reactions of TAM treatment. According to CYP2D6 genotype, it can guide the individualized administration of TAM after premenopausal and ER positive breast cancer patients.