Department of Breast Surgery, Peking University People's Hospital, Beijing, China.
Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
Hum Reprod. 2021 Mar 18;36(4):976-986. doi: 10.1093/humrep/deaa349.
Does goserelin, a GnRH agonist, have a protective effect in young breast cancer patients in terms of ovarian reserve markers anti-Müllerian hormone (AMH) and antral follicle count (AFC) during chemotherapy?
Compared with chemotherapy alone, concurrent goserelin is associated with a higher probability of ovarian reserve recovery at 1 year after chemotherapy.
Previous studies on the administration of goserelin to protect ovarian function during chemotherapy have produced conflicting results because of the endpoint used, namely, chemotherapy-induced amenorrhoea. Reproductive medicine specialists consider AMH and AFC as the most sensitive ovarian reserve markers; however, they have never been used as biomarkers to assess the potential protective effects on ovarian reserve of goserelin during chemotherapy.
STUDY DESIGN, SIZE, DURATION: This was a prospective cohort study in which patients were assigned to receive (neo)adjuvant chemotherapy with goserelin (the goserelin group) or without goserelin (the control group) according to each patient's preference. Of 242 breast cancer patients enrolled between December 2015 and November 2019, 76 in control group and 73 in goserelin group were able to be assessed at 1 year after chemotherapy.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Premenopausal patients with a regular menstrual cycle and aged 18-45 years were eligible for enrolment if they were newly diagnosed with stages I-III breast cancer for which treatment with adjuvant or neoadjuvant chemotherapy was planned. Each patient in the goserelin group was given a subcutaneous dose of 3.6 mg at least 1 week before the first cycle of chemotherapy and then every 4 weeks for the duration of chemotherapy. Ovarian reserve markers and menstrual status were evaluated before and after chemotherapy in the two treatment groups. The primary endpoint was the AMH recovery rate, the secondary endpoints were the recovery rates of AFC, estradiol (E2), follicle-stimulating hormone (FSH) and menstruation.
Among 149 patients (76 in the control group and 73 in the goserelin group) with complete data at 1 year after chemotherapy, the adjusted recovery rate of AMH was 46.5% and 21.8% in the goserelin group and control group, respectively (odds ratio: 3.08; P = 0.002). The trends in AFC and FSH recovery rates were consistent with that in AMH recovery rate. Notably, AMH levels remained low in 41.3% of patients whose menstrual activity had resumed.
LIMITATIONS, REASONS FOR CAUTION: Randomisation was not performed because of ethical considerations, so selection bias was inevitable, although propensity score weighting was done. The study was also underpowered because 21.5% (52/242) of enrolled patients received GnRH agonist-containing endocrine therapy and could not be analysed at 1 and 2 years after chemotherapy.
Our results indicate that co-administration of goserelin with chemotherapy provides obvious ovarian reserve protection in these young breast cancer patients. We expect that these results will be applicable in clinical practice for young breast cancer patients.
STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Key R&D Program of China No. 2016YFC0901302, by the Research and Development Fund of Peking University People's Hospital No. RD2014-13, RDY2017-19 and by AstraZeneca. The authors have no disclosures.
NCT02430103.
在化疗期间，促性腺激素释放激素激动剂（GnRH 激动剂）戈舍瑞林是否对年轻乳腺癌患者的卵巢储备标志物抗苗勒管激素（AMH）和窦卵泡计数（AFC）具有保护作用？
与单独化疗相比，同期戈舍瑞林与化疗后 1 年卵巢储备恢复的可能性更高。
以前关于在化疗期间给予戈舍瑞林以保护卵巢功能的研究由于使用的终点（化疗诱导的闭经）而产生了相互矛盾的结果。生殖医学专家认为 AMH 和 AFC 是最敏感的卵巢储备标志物；然而，它们从未被用作评估戈舍瑞林在化疗期间对卵巢储备潜在保护作用的生物标志物。
研究设计、规模、持续时间：这是一项前瞻性队列研究，根据每位患者的偏好，将患者分配接受（新）辅助化疗联合戈舍瑞林（戈舍瑞林组）或不联合戈舍瑞林（对照组）。在 2015 年 12 月至 2019 年 11 月期间纳入的 242 名乳腺癌患者中，对照组 76 例，戈舍瑞林组 73 例，可在化疗后 1 年进行评估。
参与者/材料、设置、方法：新诊断为 I-III 期乳腺癌且计划接受辅助或新辅助化疗的 18-45 岁有规律月经周期的绝经前患者符合入组条件。戈舍瑞林组的每位患者在化疗第一周期前至少 1 周皮下给予 3.6mg，然后每 4 周给予一次，直至化疗结束。在两组治疗中，在化疗前后评估卵巢储备标志物和月经状况。主要终点是 AMH 恢复率，次要终点是 AFC、雌二醇（E2）、卵泡刺激素（FSH）和月经恢复率。
在化疗后 1 年有完整数据的 149 名患者（对照组 76 名，戈舍瑞林组 73 名）中，戈舍瑞林组和对照组的 AMH 恢复率分别为 46.5%和 21.8%（优势比：3.08；P=0.002）。AFC 和 FSH 恢复率的趋势与 AMH 恢复率一致。值得注意的是，在月经活动恢复的 41.3%的患者中，AMH 水平仍然较低。
局限性、谨慎的原因：由于伦理考虑，未进行随机分组，因此不可避免地存在选择偏倚，尽管进行了倾向评分加权。由于 21.5%（52/242）入组患者接受了含有 GnRH 激动剂的内分泌治疗，无法在化疗后 1 年和 2 年进行分析，因此该研究也没有足够的效力。
我们的研究结果表明，戈舍瑞林联合化疗对这些年轻乳腺癌患者的卵巢储备有明显的保护作用。我们期望这些结果将适用于年轻乳腺癌患者的临床实践。
研究基金/利益冲突：本研究由国家重点研发计划（No.2016YFC0901302）、北京大学人民医院研发基金（RD2014-13、RDY2017-19 和 AstraZeneca）资助。作者没有披露。
NCT02430103。
