含蒽环类和蒽环类序贯紫杉类方案辅助化疗对早期乳腺癌患者致闭经作用的比较及影响因素分析

Comparison and analysis of influencing factors of amenorrhea due to adjuvant chemotherapies of anthracycline-based and anthracycline followed by taxen in women with early breast cancer

目的探讨含蒽环类方案和蒽环类序贯紫杉类方案辅助化疗对绝经前早期乳腺癌患者致闭经的作用及影响因素。方法收集中国医学科学院北京协和医学院肿瘤医院2008至2010年收治的雌激素受体阳性且接受含蒽环类或蒽环类序贯紫杉类方案辅助化疗的绝经前早期乳腺癌患者的病历资料进行回顾性分析。化疗方案包括含蒽环类的6EC方案(环磷酰胺600 mg/m^2+表柔比星75mg/m^2,21 d为1个周期,共6个周期)和蒽环类序贯紫杉类的4EC-4T方案(环磷酰胺600 mg/m^2+表柔比星90 mg/m^2,21 d为1个周期,共4个周期;序贯紫杉醇175 mg/m^2或多西紫杉醇75 mg/m^2,21 d为1个周期,共4个周期)。按辅助化疗方案将患者分为2组,统计化疗所致闭经(CIA)发生率,记录CIA患者化疗结束后2年内月经和卵巢功能(以卵泡刺激素、黄体生成素和雌二醇水平反映)恢复情况,采用Logistic回归方法和χ~2检验分析CIA的影响因素。结果纳入分析的患者共96例。6EC方案组45例,中位年龄43岁;4EC-4T方案组51例,中位年龄42岁。化疗结束时96例患者中77例发生CIA(80.2%),化疗后2年内CIA患者中月经恢复者51例(66.2%),卵巢功能恢复者53例(68.8%)。6EC方案组和4EC-4T方案组CIA发生率、月经恢复率和卵巢功能恢复率差异无统计学意义[75.6%(34/45)比84.3%(43/51),70.6%(24/34)比62.8%(27/43),73.5%(25/34)比65.1%(28/43),均P<0.05]。年龄是CIA转归的重要影响因素(风险比=0.759,95%置信区间为0.448~0.968,P=0.048)。年龄>40岁和≤40岁者CIA发生率分别为86.9%(53/61)和68.6%(24/35)(P=0.022),卵巢功能恢复率分别为56.6%(30/53)和100.0%(24/24)(P=0.000)。年龄≤40岁者月经恢复时间与卵巢功能恢复时间同步,年龄>40岁者月经恢复时间(中位时间11个月)晚于卵巢功能恢复时间(中位时间9个月)。结论含蒽环类方案和蒽环类序贯紫杉类方案辅助化疗均可导致绝经前早期乳腺癌患者发生CIA,两组CIA的发生率及转归相似。年龄是CIA发生及其转归的重要影响因素。对于发生CIA的年轻患者,术后辅助化疗后的内分泌治疗选择应慎重。

Objective To determine the effect and influence factors of amenorrhea due to adjuvant chemotherapies of anthracyeline-based and anthracycline followed by taxen in premenopausal patients with early breast cancer. Methods Case records of the patients who were premeriopausal and estrogen receptor-positive with early breast cancer and received adjuvant chemotherapies of anthracycline-based and anthracycline followed by taxen in Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College from 2008 to 2010 were collected and retrospectively analysed. The chemotherapy regimens included anthracycline-based regimen 6EC （ epirubicin 75 mg/m2 and cyclophosphamide 600 mg,/m2 for 6 cycles and each cycle taking 21 days ） and the anthracycline followed by taxen regimen 4EC-4T （ epimbicin 90 mg/m2 and cyclophosphamide 600 mg/m2 for 4 cycles and each cycle taking 21 days, followed by paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 for 4 cycles and each cycle taking 21 days）. The patients were divided into two groups by the regiments. The incidence of chemotherapy-induced amenorrhea （CIA） was calculated and the recovery situation of menses and ovarian function in the patients with CIA during two years after the end of chemotherapy was recorded. The ovarian function was showed by luteinizing hormone, follicle-stimulating hormone, and estradiol levels. Influence factors of C1A was analysed in Logistic regression and X2 test methods. Results Ninety-six patients were enrolled in this study. Of them, 45 patients were in the 6EC group with a media age of 43-year-old and 5l patients were in the 4EC-4T group with a media age of 42-year-old. Seventy-seven of ninety-six patients （ 80.2% ） suffered from CIA during two years after the end of chemotherapy. Of the 77 patients with CIA, 51 patients＇menses （66.2%） normalized and 53 patients＇ ovarian function （68.8%） normalized during the two years after the end of chemotherapy. There were no statistical differences in the CIA incidence, the rate of recovery of menses, and the rate of recovery of ovarian function between the 4EC-4T and the 6EC groups [ 75.6% （34/45） vs. 84.3% （43/51）, 70.6% （24/34）vs. 62.8% （27/43）, 73.5% （25/34）vs. 65.1% （28/43）, P〉 0. 05 for all the comparisons]. Age was an important influence factor of outcome of CIA [ P = 0. 048, hazard ratio =0. 759, 95% confidence interval （0.448, 0. 968） ]. The incidences of CIA and the rates of recovery of ovarian function in the patients aged 〉40 years and the patients aged ≤40 years were 86.9% （53/61） vs. 68. 6% （24/35） , 56.6% （30/53） vs. 100.0% （24/24） respectively, （P = 0.022, P = 0. 000）. The time of menses recovery synchronized with the time of ovarian function recovery in the patients aged ≤ 40 years and the time of menses recovery （a median time of 11 months） was later than the time of ovarian function recovery （ a median time of 9 months ） in the patients aged 〉 40 years. Conclusions Both anthracycline-based and anthracycline followed by taxen regiments can induce CIA in the premenopausal patients with early breast cancer and the incidence and outcome of the two groups are similar. Age is an important influence factor of the incidence and outcome of CIA. The choice of endocrinotherapy after postoperation chemotherapy for the younger patients with CIA should be careful.