Wang S Y, Wang S
Department of Breast Surgery, Peking University People's Hospital, Beijing 100044, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2019 Jun 18;51(3):536-541. doi: 10.19723/j.issn.1671-167X.2019.03.024.
To observe the dynamic change of anti-Müllerian hormone (AMH) in 1 year after chemotherapy which is the best biochemical marker of ovarian reserve in reproductive medicine setting and to evaluate the effect of gonadotropin-releasing hormone agonist (GnRHa)goserelin to prevent ovarian reserve function during (neo)adjuvant chemotherapy for young breast cancer patients.
Between December 2015 and June 2017, 101 breast cancer patients of age ≤ 45 years with stages I to III had been enrolled. The patients were assigned without interference to receive either (neo) adjuvant chemotherapy with goserelin (goserelin group) or without goserelin (chemotherapy group) as their own selection. AMH and menstrual status were evaluated before, during and 0.5 year, 1 year after chemotherapy. Primary end point was the incidence of low AMH value (<0.4 μg/L) at the end of 1 year. Secondary end point was the incidence of amenorrhea (the absence of menses in the preceding 12 months after assignment).
In the study, 51 patients chose to join the chemotherapy group, while the other 50 patients selected goserelin to preserve their ovarian reserve function. More unmarried or childless, hormone receptors negative,receiving breast conservation therapy patients with earlier stage selected goserelin before chemotherapy. The incidence of low AMH value was significantly higher in chemotherapy group than in goserelin group (74.5% vs. 38.0%, P<0.001) in 1 year after chemotherapy. The incidence of amenorrhea was consistent with AMH (56.9% vs. 24.0%, P=0.001). And more patients' menstruation (78.9% vs. 54.5%) and AMH value (71.0% vs. 53.8%) recovered in goserelin group within 6 months after chemotherapy. In subgroup analysis, AMH and menstruation seemingly recovered more in goserelin group independent of age, chemotherapy regimen and use of tamoxifen. Especially, AMH value of 36.4% (8/22) patients in chemotherapy group and 18.4% (7/38) patients in goserelin group still maintained low level (<0.4 μg /L) although their menstruation had recovered 1 year after chemotherapy. In addition, 41 patients (20 patients in chemotherapy group, 21 patients in goserelin group) could be evaluated for the dynamic change of AMH and menstrual status during chemotherapy. The mean level of AMH in chemotherapy group declined rapidly to very low level before the 3rd cycle, while 70% of the patients kept presence of menstruation. At the same time, the mean level of AMH in goserelin group was still above 0.4 μg /L, but all of the patients had menopause.
Our study has offered evidence that Goserelin with chemotherapy could protect against ovarian reserve failure for young breast cancer patients, now that more patients' AMH value recovered earlier who had selected co-treatment. AMH may be a more precise marker than menstrual status to clinically evaluate ovarian reserve function pre-, during and post- chemotherapy.
观察抗苗勒管激素（AMH）在化疗后1年内的动态变化，AMH是生殖医学领域评估卵巢储备功能的最佳生化标志物，并评估促性腺激素释放激素激动剂（GnRHa）戈舍瑞林在年轻乳腺癌患者（新）辅助化疗期间对卵巢储备功能的保护作用。
2015年12月至2017年6月，纳入101例年龄≤45岁、分期为Ⅰ至Ⅲ期的乳腺癌患者。患者自行选择，无干预地接受含戈舍瑞林的（新）辅助化疗（戈舍瑞林组）或不含戈舍瑞林的化疗（化疗组）。在化疗前、化疗期间以及化疗后0.5年、1年评估AMH和月经状态。主要终点是化疗1年末AMH值低（<0.4μg/L）的发生率。次要终点是闭经的发生率（入组后前12个月无月经）。
研究中，51例患者选择加入化疗组，另外50例患者选择戈舍瑞林以保留其卵巢储备功能。更多未婚或未育、激素受体阴性、接受保乳治疗且分期较早的患者在化疗前选择了戈舍瑞林。化疗后1年，化疗组AMH值低的发生率显著高于戈舍瑞林组（74.5%对38.0%，P<0.001）。闭经发生率与AMH情况一致（56.9%对24.0%，P=0.001）。化疗后6个月内，戈舍瑞林组更多患者月经（78.9%对54.5%）和AMH值（71.0%对53.8%）恢复。在亚组分析中，无论年龄、化疗方案和他莫昔芬的使用情况如何，戈舍瑞林组AMH和月经恢复情况似乎更好。特别是，化疗组36.4%（8/22）的患者和戈舍瑞林组18.4%（7/38）的患者在化疗后1年月经已恢复，但AMH值仍维持在低水平（<0.4μg/L）。此外，41例患者（化疗组20例，戈舍瑞林组21例）可评估化疗期间AMH和月经状态的动态变化。化疗组AMH平均水平在第3周期前迅速降至极低水平，而70%的患者仍有月经。同时，戈舍瑞林组AMH平均水平仍高于0.4μg/L，但所有患者均出现闭经。
我们的研究提供了证据表明，戈舍瑞林联合化疗可预防年轻乳腺癌患者卵巢储备功能衰竭，因为选择联合治疗的更多患者的AMH值更早恢复。AMH可能是比月经状态更精确的标志物，用于临床评估化疗前、化疗期间及化疗后的卵巢储备功能。
