Dezellus A, Barriere P, Campone M, Lemanski C, Vanlemmens L, Mignot L, Delozier T, Levy C, Bendavid C, Debled M, Bachelot T, Jouannaud C, Loustalot C, Mouret-Reynier M A, Gallais-Umbert A, Masson D, Freour T
Service de médecine et biologie du développement et de la reproduction, CHU de Nantes, Nantes, France; Institut de Cancérologie de l'Ouest et INSERM UMR 892 - 6299 CNRS, Nantes, France.
Service de médecine et biologie du développement et de la reproduction, CHU de Nantes, Nantes, France; INSERM UMR 1064 - ITUN, Nantes, France; Faculté de médecine, Université de Nantes, Nantes, France.
Eur J Cancer. 2017 Jul;79:72-80. doi: 10.1016/j.ejca.2017.03.035. Epub 2017 Apr 29.
Women of reproductive age with breast cancer generally receive gonadotoxic chemotherapy. Fertility issues are of great concern for them. However, little is known on ovarian damage during chemotherapy and its evolution during long-term follow-up. The aim of this study was to provide a detailed description of serum anti-Müllerian hormone (AMH) evolution during chemotherapy and 24-month follow-up.
This prospective cohort study was conducted in 250 patients, aged 18-39 years, diagnosed with breast cancer and treated with adjuvant/neoadjuvant chemotherapy. Each patient underwent blood AMH measurement at each chemotherapy cycle, and at 6, 12 and 24 months after chemotherapy. Menses occurrence was also recorded.
Mean basal AMH level was 4.19 ± 4.84 ng/mL, and was negatively correlated with age. Serum AMH level rapidly decreased in all patients after each chemotherapy cycle to undetectable levels in most of them, and slowly increased in 45% of the patients during the 24-month follow-up. AMH decrease was significantly associated with age and basal AMH level, but not with cyclophosphamide dose and tamoxifen use. The prevalence of chemotherapy-related amenorrhoea was 92.4% at the end of chemotherapy; women with amenorrhoea being significantly older and having lower basal AMH than women who resumed menses.
Our study confirms rapid and deep ovarian reserve alteration in young women receiving chemotherapy for breast cancer, and shows moderate AMH recovery in some patients. Although AMH cannot alone predict fertility potential, these new data emphasise the need for post-treatment ovarian insufficiency follow-up, strongly support the use of fertility preservation strategies and may provide new tools for improved counselling.
患有乳腺癌的育龄女性通常会接受具有性腺毒性的化疗。生育问题是她们极为关注的。然而,关于化疗期间卵巢损伤及其在长期随访中的演变情况却知之甚少。本研究的目的是详细描述化疗期间及24个月随访期内血清抗苗勒管激素(AMH)的变化情况。
本前瞻性队列研究纳入了250例年龄在18至39岁之间、被诊断为乳腺癌并接受辅助/新辅助化疗的患者。每位患者在每个化疗周期以及化疗后6个月、12个月和24个月时均接受血液AMH检测。同时记录月经来潮情况。
平均基础AMH水平为4.19±4.84 ng/mL,且与年龄呈负相关。所有患者在每个化疗周期后血清AMH水平迅速下降,大多数患者降至检测不到的水平,45%的患者在24个月随访期间缓慢上升。AMH下降与年龄和基础AMH水平显著相关,但与环磷酰胺剂量和他莫昔芬的使用无关。化疗结束时化疗相关闭经的发生率为92.4%;闭经女性的年龄明显更大,基础AMH水平低于恢复月经的女性。
我们的研究证实了接受乳腺癌化疗的年轻女性卵巢储备迅速且深度改变,并显示部分患者AMH有中度恢复。虽然AMH不能单独预测生育潜力,但这些新数据强调了治疗后卵巢功能不全随访的必要性,有力支持了生育力保存策略的应用,并可能为改善咨询提供新工具。