基于CYP2D6多态性晚期乳腺癌内分泌解救策略的研究

目的:探讨大剂量托瑞米芬能否克服乳腺癌CYP2D6*10代谢缺陷，为晚期激素受体阳性乳腺癌患者寻求一种廉价有效的解救策略。方法:选取我院2015年1月至2018年6月收治的晚期乳腺癌患者95例，用PCR方法检测CYP2D6基因多态性。对于CYP2D6*10型患者，按照最佳三阶段设计原则，给予托瑞米芬120 mg每天一次。按修订的实体瘤疗效评价标准评价治疗效果。结果:95例晚期乳腺癌患者中，Wt/Wt 型28例（29.5%），Wt/*10型49例(51.6%)，*10/*10型18例(18.9%)。χ2检验显示CYP2D6 基因多态性与年龄、组织类型、Ki67高低、内脏转移、转移数目等均无明显相关性。第二阶段纳入41例患者，疾病稳定患者仅为10例，遂终止研究。*10/*10型患者疾病控制率为33.3%(5/15)，Wt/*10型患者疾病控制率为19.2%(5/26)。3例PR患者均来自*10/*10组。中位随访46个月，*10/*10型患者和Wt/*10型患者OS分别为41个月和43个月，无统计学差异，P=0.327。结论:总体而言，在他莫昔芬治疗失败后CYP2D6*10型乳腺癌患者继续用大剂量托瑞米芬来解救获益不明显，但对于CYP2D6*10/*10亚型的患者，托瑞米芬可能有潜在的解救价值。

Salvage endocrine strategy for metastatic breast cancer

Objective:To explore whether the CYP2D6 metabolic defect can be conquered by high dose toremifene or not，searching a new and affordable salvage treatment for hormone receptor positive metastatic breast cancer.Methods:From 2015 January to 2018 June，the CYP2D6 polymorphisms were detected in 95 metastatic breast cancer patients using polymerase chain reaction method.The patients with CYP2D6*10 subtype were administered toremifene 120 mg daily according to optimal three-stages designs.Tumor response was based on the modified response evaluation in solid tumor.Results:CYP2D6 Wt/Wt subtype had 28 cases (29.5%)，Wt/*10 subtype 49 cases (51.6%) and *10/*10 subtype 18 cases (18.9%) in 95 metastatic breast cancer patients.χ2 test showed CYP2D6 genotype was not significantly correlated with age，histology，Ki67，visceral involvement and metastatic sites.The trial was closed in second stage because only 10 patients had achieved disease control out of 41 patients.The disease control rate was 33.3%(5/15) in patients with CYP2D6*10/*10 subtype and 19.2%(5/26) in Wt/*10 subtype.Three partial response cases were all out of CYP2D6*10/*10 subtype.With a median follow-up of 46 months，there was no significant difference in overall survival between *10/*10 subtype and Wt/*10 subtype (41 months vs 43 months respectively，P=0.327).Conclusion:Generally，high dose toremifene could not gain benefit to CYP2D6*10 breast cancer patients previously treated with tamoxifen.But for CYP2D6*10/*10 subtype，toremifene may play a potential role in salvage setting.