早期乳腺癌患者化疗联合促性腺激素释放激素激动剂：一项单中心、双盲、随机对照临床试验

doi:10.3969/j.issn.1009-976X.2022.01.002

岭南现代临床外科 ›› 2022, Vol. 22 ›› Issue (01): 7-13.DOI: 10.3969/j.issn.1009-976X.2022.01.002

早期乳腺癌患者化疗联合促性腺激素释放激素激动剂：一项单中心、双盲、随机对照临床试验

林威威¹, 林确然^2,3, 何钻玉⁴, 苏逢锡^2,3, 潘萍¹, 陈凯^2,3,*, 杨冬梓^1,*

1.中山大学孙逸仙纪念医院妇产科,广州510120;
2.广东省恶性肿瘤表观遗传与基因调控重点实验室,广州 510120;
3.中山大学孙逸仙纪念医院逸仙乳腺肿瘤医院乳腺外科,广州 510120;
4.卓祥医疗门诊部,广州510410

通讯作者: *杨冬梓, Email：yangdz@mail.sysu.edu.cn;陈凯, Email：chenkai23@mail.sysu.eu.cn; ckaichen@126.com.
基金资助:
中山大学5010项目（2007-017）; 广州再生医学与健康广东省实验室临床创新研究项目（2018GZR0201004）; 广州市科技计划项目中国乳腺癌产学研创新联盟（20212200003）; 广州市市校（院）联合资助（登峰医院）基础研究项目（202102010221）

Chemotherapy combined with gonadotropin-releasing hormone agonist in early breast cancer patients： a single-centre, double-blind, randomized controlled trial

LIN Wei-wei¹, LIN Que-ran^2,3, HE Zuan-yu⁴, SU Feng-xi^2,3, PAN Ping¹, CHEN Kai^2,3, YANG Dong-zi^1,*

1. Department of Obstetrics and Gynecology;
2. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation;
3. Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China;
4. Zhuoxiang Medical Out-patient Centre, Guangzhou 510410,China

Received:2022-01-20 Online:2022-03-17 Published:2022-03-17
Contact: YANG Dong-zi, yangdz@mail.sysu.edu.cn; CHEN Kai, chenkai23@mail.sysu.eu.cn; ckaichen@126.com

摘要/Abstract

摘要： 目的分析化疗联合促性腺激素释放激素激动剂（GnRHa）对于乳腺癌患者化疗后月经恢复的情况,并探讨GnRHa的应用对患者的潜在副作用。方法本研究是一项单中心,双盲,随机对照临床试验。共纳入了141名年龄从14 ~ 45岁的女性乳腺癌早、中期患者并采用SPSS软件生成随机码把患者随机分为干预组（n = 69）和对照组（n = 72）。随访在中山大学孙逸仙纪念医院进行,从2008年8月到2021年12月结束。使用Logistic回归来研究GnRHa对化疗结束后患者月经恢复的疗效,线性回归研究GnRHa与肝功能指标和卵泡计数的关系,Cox回归分析月经恢复与否对于患者预后的影响。结果化疗结束六个月后,干预组患者有69.2%恢复月经,同比对照组为75.9%,差异无统计学意义（P > 0.05）。多因素logistic回归显示使用GnRHa与否对月经恢复无显著影响（OR=0.19,95% CI：0.03 ~ 1.14）;对丙氨酸转氨酶、窦卵泡计数均无显著副作用（P > 0.05）。Cox回归显示月经恢复与否死亡,转移和复发无显著联系（P > 0.05）,右侧卵巢容积与转移呈显著负相关（HR=0.76;P = 0.046）。Log-rank test结果显示干预组与对照组的无转移生存期（MFS）和无复发生存期（RFS）无显著差异（P > 0.05）。结论在乳腺癌患者化疗中配合使用GnRHa对化疗后月经恢复率无显著影响,使用GnRHa安全性较高,无显著肝脏毒性。

关键词: 乳腺癌, 化疗, 促性腺激素释放激素激动剂, 月经恢复

Abstract: Objective To analyze the effect of chemotherapy combined with gonadotropin-releasing hormone （GnRHa） on the menstrual recovery of breast cancer patients after chemotherapy and explore the potential side effects of GnRHa on patients. Methods This is a single-centre, double-blind, randomized clinical trial. A total of 141 early- or middle-stage breast cancer patients aged 14 ~ 45 years were included. The patients were randomly assigned to the intervention group （n=69） and control group （n=72） using random digits generated by SPSS. The follow-up was conducted in Sun Yat-sen Memorial Hospital, Sun Yat-sen University from August 2008 to December 2021. Logistic regression was used to study the effect of GnRHa on menstrual recovery after chemotherapy, linear regression was used to study the relationship between GnRHa and liver function indicator and antral follicle count （AFC）, and Cox regression was used to analyze the impact of menstrual recovery on the prognosis of patients. Results At six months after chemotherapy, 69.2% of the patients in the intervention group recovered menstruation compared with 75.9% in the control group, with no statistically significant difference （P>0.05）. Multivariate logistic regression showed that the use of GnRHa had no significant effect on menstrual recovery （OR=0.19, 95% CI： 0.03~1.14）; no significant side effects on alanine aminotransferase and AFC （P> 0.05）. There were no significant associations between menstrual recovery with death, metastasis, and relapse （P>0.05）. The average volume of the right ovarian was significantly negatively associated with metastasis （HR=0.76; P=0.046）. The Log-rank test indicated no significant difference in metastasis-free survival （MFS） and relapse-free survival （RFS） between the intervention group and the control group （P>0.05）. Conclusion The use of GnRHa in chemotherapy among breast cancer patients had no significant effect on the menstrual recovery after chemotherapy. The safety of using GnRHa was high and there was no significant hepatotoxicity.

Key words: breast cancer, chemotherapy, gonadotropin-releasing hormone agonists, menstrual recovery

中图分类号:

R735.7

林威威, 林确然, 何钻玉, 苏逢锡, 潘萍, 陈凯, 杨冬梓. 早期乳腺癌患者化疗联合促性腺激素释放激素激动剂：一项单中心、双盲、随机对照临床试验[J]. 岭南现代临床外科, 2022, 22(01): 7-13.

LIN Wei-wei, LIN Que-ran, HE Zuan-yu, SU Feng-xi, PAN Ping, CHEN Kai, YANG Dong-zi. Chemotherapy combined with gonadotropin-releasing hormone agonist in early breast cancer patients： a single-centre, double-blind, randomized controlled trial[J]. Lingnan Modern Clinics In Surgery, 2022, 22(01): 7-13.

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早期乳腺癌患者化疗联合促性腺激素释放激素激动剂：一项单中心、双盲、随机对照临床试验

Chemotherapy combined with gonadotropin-releasing hormone agonist in early breast cancer patients： a single-centre, double-blind, randomized controlled trial

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