曼月乐对口服他莫昔芬的乳腺癌患者子宫内膜保护作用的Meta分析

The Meta-analysis Protective Effect of Mirena on Endometrial Protection in Breast Cancer Patients Taking Oral Tamoxifen

目的系统评价使用曼月乐对乳腺癌术后口服他莫昔芬内分泌治疗的患者进行保护子宫内膜的临床疗效和安全性。方法通过计算机检索PubMed(1966年1月至2021年10月),Cochrane临床对照试验注册资料库、EMbase,中国知网数据库,收集乳腺癌术后长期口服他莫昔芬的患者,同时使用曼月乐进行子宫内膜保护的临床随机对照试验(RCT)。采用RevMan 5.4软件分析子宫内膜息肉发生率、子宫内膜增生发生率、子宫内膜癌发生率、子宫肌瘤发生率、异常子宫出血发生率、乳腺癌复发发生率、乳腺癌相关病死率等相关指标。结果最终6篇文献被纳入本研究,包含629例乳腺癌患者。Meta分析结果显示:①使用曼月乐明显降低了子宫内膜息肉发生率[OR=0.22,95%CI(0.14~0.36),P<0.00001]。同时,曼月乐降低了子宫内膜增生的发生率[OR=0.13,95%CI(0.03~0.67),P<0.00001]。而曼月乐+他莫昔芬组与他莫昔芬组两组之间的肌瘤发病率几乎没有差异[OR=0.56,95%CI(0.19~1.63),P=0.29]。②曼月乐增加了异常子宫出血的发生率[OR=5.07,95%CI(2.71~9.52),P<0.00001]。两组之间的乳腺癌复发率及乳腺癌相关的病死率无显著差异[复发率OR=1.74,95%CI(0.64~4.74),P=0.28;病死率OR=1.02,95%CI(0.36~2.84),P=0.97]。结论曼月乐对长期口服他莫西芬治疗的乳腺癌患者的子宫内膜良性病变有保护作用。能降低了子宫内膜息肉、子宫内膜增生的发生率,但放置曼月乐1年内增加了异常子宫出血的发生率,尚不明确其对于子宫肌瘤发病率、乳腺癌的复发率及病死率的影响。

Objective To systematically evaluate the clinical efficacy and safety of endometrial protection in patients treated with oral tamoxifen endocrine therapy for postoperative breast cancer using Mirena.Methods A computer search of PubMed(January 1966 to October 2021),the Cochrane Register of Controlled Clinical Trials,EMbase,and the China Knowledge Base database was conducted to collect patients on long-term oral tamoxifen after breast cancer surgery,along with a clinical randomized controlled trial(RCT)of endometrial protection with Mirena.RevMan 5.4 software was used to analyses the incidence of endometrial polyps,incidence of endometrial hyperplasia,incidence of endometrial cancer,incidence of uterine fibroids,incidence of abnormal uterine bleeding,incidence of breast cancer recurrence,breast cancer-related mortality and other relevant indicators.Results The final 6 publications were included in this study,containing 629 breast cancer patients.the results of the Meta-analysis showed that:(1)the use of Mirena significantly reduced the incidence of endometrial polyps[OR=0.22,95%CI(0.14-0.36),P<0.00001].At the same time,the Mirena ring reduced the incidence of endometrial hyperplasia[OR=0.13,95%CI(0.03-0.67),P<0.00001].In contrast,there may be almost no difference in the incidence of myomas between the Mirena+tamoxifen and tamoxifen groups[OR=0.56,95%CI(0.19-1.63),P=0.29].(2)Mirena increases the incidence of abnormal uterine bleeding[OR=5.07,95%CI(2.71-9.52),P<0.00001].There was no significant difference in the recurrence rate of breast cancer and breast cancer-related mortality between the two groups[recurrence rate OR=1.74,95%CI(0.64-4.74),P=0.28;mortality rate OR=1.02,95%CI(0.36-2.84),P=0.97].Conclusion The Mirena ring was protective against benign endometrial lesions in breast cancer patients treated with long-term oral tamoxifen.It reduced the incidence of endometrial polyps and endometrial hyperplasia,but increased the incidence of abnormal uterine bleeding within 1 year of placement of the Mirena ring.It is unclear what effect it has on the incidence of uterine fibroids,the recurrence rate of breast cancer and mortality.