早期乳腺癌绝经前患者化疗期间
促性腺激素释放激素激动剂对于
卵巢功能和生育能力的保护作用
患者个体数据系统回顾荟萃分析
编者按：早期乳腺癌绝经前女性化疗期间，利用瑞林类促性腺激素释放激素激动剂（例如曲普瑞林、戈舍瑞林、亮丙瑞林、戈那瑞林、布舍瑞林、组氨瑞林、那法瑞林、德舍瑞林、舍莫瑞林）暂时抑制卵巢，作为卵巢功能和生育能力的保护措施，既往随机对照研究结果不一，仍然存在争议。
2018年5月2日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表比利时布鲁塞尔自由大学、美国克利夫兰医院、旧金山加利福尼亚大学、西南肿瘤协作组（SWOG）统计中心、西雅图华盛顿大学弗雷德·哈金森癌症研究中心、南佛罗里达大学莫菲特癌症中心、芝加哥洛约拉大学、达拉斯次世代肿瘤医院、哈佛大学达纳法伯癌症研究所、英国伦敦帝国学院、爱丁堡大学、邓迪大学奈威尔斯医院、苏塞克斯癌症中心、德国乳腺癌协作组、罗斯托克大学医院、意大利热那亚大学圣马蒂诺综合医院、佛罗伦萨大学卡勒吉医院的研究报告，通过患者个体水平数据系统回顾与荟萃分析，评定了瑞林类保护早期乳腺癌绝经前患者化疗期间卵巢功能和生育能力的有效性和安全性。
作者通过PubMed、Embase、Cochrane数据库对2015年4月30日之前公开发表的早期乳腺癌绝经前女性接受（新）辅助化疗±瑞林类随机对照研究报告进行了系统回顾，并于2017年8月31日进行荟萃分析。主要终点为早期卵巢功能不全（卵巢早衰）率和治疗后妊娠率。次要终点为无病生存和总体生存。由于各个研究均为独立分组，故通过随机效应模型进行统计学分析。
结果发现共有5项研究873例患者符合要求：
PROMISE-GIM6（NCT00311636）281例±曲普瑞林
POEMS/S0230（NCT00068601）257例±戈舍瑞林
OPTION（NCT00427245）227例±戈舍瑞林
GBG-37 ZORO（NCT00196846）60例±戈舍瑞林
MCC-0203（NCT00090844）48例±曲普瑞林
瑞林组与对照组相比：
卵巢早衰率较低：14.1%比30.9%（校正比值比：0.38，95%置信区间：0.26～0.57，P<0.001）
治疗后妊娠较多：10.3%比 5.5%（发生率比值：1.83，95%置信区间：1.06～3.15，P=0.030）
无病生存率相似：79.5%比80.0%（校正风险比：1.01，95%置信区间：0.72～1.42，P=0.999）
总体生存率相似：90.2%比86.3%（校正风险比：0.67，95%置信区间：0.42～1.06，P=0.083）
因此，该研究结果为早期乳腺癌绝经前患者化疗期间利用瑞林类促性腺激素释放激素激动剂暂时抑制卵巢作为可选手段减少化疗引起卵巢早衰可能并且潜在改善将来生育能力的有效性和安全性提供了证据。
对此，以色列理工大学医学院妇产科学教授、迈蒙尼德医院生殖内分泌科主任兼女性健康中心主任发表编者评论：利用促性腺激素释放激素激动剂抑制卵巢功能保护生育能力的争议可以盖棺定论了吗？
读者调查
相关阅读
J Clin Oncol. 2018 May 2. [Epub ahead of print]
Gonadotropin-Releasing Hormone Agonists During Chemotherapy for Preservation of Ovarian Function and Fertility in Premenopausal Patients With Early Breast Cancer: A Systematic Review and Meta-Analysis of Individual Patient-Level Data.
Lambertini M, Moore HCF, Leonard RCF, Loibl S, Munster P, Bruzzone M, Boni L, Unger JM, Anderson RA, Mehta K, Minton S, Poggio F, Albain KS, Adamson DJA, Gerber B, Cripps A, Bertelli G, Seiler S, Ceppi M, Partridge AH, Del Mastro L.
Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium; Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Imperial College, London; University of Edinburgh, Edinburgh; Ninewells Hospital, Dundee; Sussex Cancer Centre, Brighton, United Kingdom; German Breast Group, Neu-Isenburg; University Hospital Rostock, Rostock, Germany; University of California, San Francisco, San Francisco, CA; Ospedale Policlinico San Martino; University of Genova, Genova; Azienda Ospedaliero Universitaria Careggi, Florence, Italy; SWOG Statistical Center and Fred Hutchinson Cancer Research Center, Seattle, WA; Moffitt Cancer Center, Tampa, FL; Loyola University Chicago Stritch School of Medicine, Maywood, IL; Nexgen Oncology, Dallas, TX; Dana-Farber Cancer Institute, Boston, MA.
PURPOSE: The role of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal women remains controversial. This systematic review and meta-analysis using individual patient-level data was conducted to better assess the efficacy and safety of this strategy in patients with early breast cancer.
METHODS: The trials in which premenopausal women with early breast cancer were randomly assigned to receive (neo)adjuvant chemotherapy alone or with concurrent GnRHa were eligible for inclusion. Primary end points were premature ovarian insufficiency (POI) rate and post-treatment pregnancy rate. Disease-free survival and overall survival were secondary end points. Because each study represents a cluster, statistical analyses were performed using a random effects model.
RESULTS: A total of 873 patients from five trials were included. POI rate was 14.1% in the GnRHa group and 30.9% in the control group (adjusted odds ratio, 0.38; 95% CI, 0.26 to 0.57; P < .001). A total of 37 (10.3%) patients had at least one post-treatment pregnancy in the GnRHa group and 20 (5.5%) in the control group (incidence rate ratio, 1.83; 95% CI, 1.06 to 3.15; P = .030). No significant differences in disease-free survival (adjusted hazard ratio, 1.01; 95% CI, 0.72 to 1.42; P = .999) and overall survival (adjusted hazard ratio, 0.67; 95% CI, 0.42 to 1.06; P = .083) were observed between groups.
CONCLUSION: Our findings provide evidence for the efficacy and safety of temporary ovarian suppression with GnRHa during chemotherapy as an available option to reduce the likelihood of chemotherapy-induced POI and potentially improve future fertility in premenopausal patients with early breast cancer.
PMID: 29718793
DOI: 10.1200/JCO.2018.78.0858
J Clin Oncol. 2018 May 2. [Epub ahead of print]
Fertility Preservation by Endocrine Suppression of Ovarian Function Using Gonadotropin-Releasing Hormone Agonists: The End of the Controversy?
Blumenfeld Z.
Technion-Israel Institute of Technology, Haifa, Israel.
PMID: 29718789
DOI: 10.1200/JCO.2018.78.9347
联系客服
