绝经前乳腺癌化疗致闭经相关因素分析及绝经评估的研究  

Analysis and Identification of Factors in Chemotherapy-Induced Amenorrhea and Menstrual Status

作　　者：吴卿[1] 谢贤和[1] WU Qing;XIE Xianhe(Department of Chemotherapy,The First Affiliated Hospital of FujianMedical University,Fuzhou 350005,China)

机构地区：[1]福建医科大学附属第一医院化疗科,福州350005

出　　处：《福建医科大学学报》2019年第1期33-39,共7页Journal of Fujian Medical University

基　　金：福建医科大学女性研究课题(2016FN008)

摘　　要：目的探讨绝经前乳腺癌化疗致闭经(CIA)的影响因素,了解化疗后卵巢功能的变化规律及CIA与绝经的关系。方法回顾性收集300例接受化疗(至少4个周期)的绝经前乳腺癌的临床资料,记录患者的年龄、病理类型、肿块分期、腋窝淋巴结转移数、激素受体、人表皮生长因子受体-2(HER-2)、化疗方案、放疗、内分泌治疗、靶向治疗、月经变化等情况和血清性激素水平[卵泡剌激素(FSH),黄体生成素(LH),雌二醇(E2)]并进行分析。采用ROC曲线、Fisher精确概率检验及卡方检验分析各因素与CIA之间的关系。使用Kaplan-Meier生存分析统计CIA发生时间与性激素水平达到绝经时间的差异。结果 204例患者出现CIA,年龄与CIA发生具有明显相关性,曲线下面积为0.899(P<0.001,95%CI:0.863～0.935),年龄影响CIA的最佳临界值为43岁。CIA的发生与病理类型、肿块分期、腋窝淋巴结转移数、雌激素受体(ER)、孕激素受(PR)、HER-2状态无关、化疗方案、是否放疗、曲妥珠单抗靶向治疗、内分泌治疗无关(P>0.05)。CIA患者中,年龄≤45岁者更易恢复月经(91.4%vs 35.8%,P<0.001),月经恢复的中位时间为6.7月(3.0～11.3月);绝经更多见于年龄>45岁者(1.4%vs 50.0%,P<0.001)。Kaplan-Meier分析显示,CIA的发生时间明显早于性激素水平达到绝经的时间(2.6月vs 13.6月,P<0.001);在46～50岁、>50岁两个年龄组中,CIA均明显早于性激素水平达绝经的时间[(2.6月vs 17.2月,P<0.001),(1.9月vs 12.1月,P<0.001)]。结论年龄是CIA发生、月经恢复的独立且具有预测意义的重要影响因素。绝经多发生在确诊乳腺癌时年龄>45岁的患者,月经恢复多见于≤45岁患者。CIA的发生明显早于性激素水平达绝经状态,这一时间间隔对乳腺癌患者出现CIA后绝经状态的判断具有重要的参考价值,对合理选择内分泌治疗药物具有重要的临床意义。Objective To investigate influencing factors of Chemotherapy-Induced Amenorrhea (CIA) and identify their ovarian function and actual menstrual status.Methods Patients with premenopausal breast cancer undergoing at least 4 cycles of chemotherapy were recruited. The patient′s age, pathological type, tumor stage, the number of axillary lymph node metastasis, the hormone receptor, HER-2, chemotherapy, radiotherapy, endocrine therapy, targeted therapy, the changes of menstruation, and serum sex hormone levels (FSH, LH, E2) were analyzed. ROC curve, Fisher′s exact probability test, and chi-square test were used to determine the relationship between the factors and CIA.Meanwhile, Kaplan Meier-survival was applied to analyze the interval between CIA and menopause. Results The CIA was observed in 204 patients. Age exhibited apparent correlation with the CIA, AUC 0.899 ( P <0.001 ,95% CI : 0.863~0.935) and the CIA′s best threshold was 43. The occurrence of CIA was not significantly associated with tumor stage, pathological type, the number of axillary lymph node metastasis, the status of ER, PR, and HER-2, chemotherapy regimens, whether received radiotherapy,targeted therapy or endocrine therapy ( P >0.05). Among the individuals with CIA, age less than or equal to 45 years old were more likely to restore menstruation (91.4% vs 35.8%, P <0.001), the median time of menstrual recovery was 6.7 months (3.0~11.3 months). Menopause generally occurred in cases over 45 years old (1.4% vs 50.0%, P <0.001).Through Kaplan Meier-analysis, the time of CIA occurred evidently earlier than menopause (2.6 months vs 13.6 months, P <0.001);in the group of 46~50 years old and over 50 years old, the time interval was significantly (2.6 months vs 17.2 months, P <0.001;1.9 months vs 12.1 months, P <0.001). Conclusions Age is an independent and major predictor for the occurrence of CIA, menstrual resumption, and menopause. Menopause generally occurs in patients over 45 years old, while menstruation recovery is found in patients less than or

关 键 词：乳腺肿瘤 化学疗法 辅助 年龄因素 闭经 

分 类 号：R45[医药卫生—治疗学] R711.51[医药卫生—临床医学]