摘要
目的分析吡咯替尼治疗HER-2阳性乳腺癌患者的疗效并建立HER-2阳性乳腺癌预后预测模型。方法采取回顾性队列研究,收集2020年5月至2023年5月在四川省岳池县人民医院治疗的250例HER-2阳性乳腺癌患者临床资料,吡咯替尼联合常规化疗的125例患者为观察组,常规化疗的125例患者为对照组。2组患者化疗疗效、不良反应发生率的比较采用χ^(2)检验。采用Kaplan-Meier法分析2组患者的无进展生存期(PFS),2组患者的PFS比较采用对数秩检验。采用COX比例风险模型对可能影响HER-2阳性乳腺癌预后不良的因素进行多因素分析。采用简单随机抽样法,将患者分为建模组与验证组(7∶3比例),使用R 4.1.0软件及rms包,建立HER-2阳性乳腺癌患者预后不良预测模型,Bootstrap法计算一致性指数(C-index)。绘制受试者操作特征曲线(ROC),计算曲线下面积(AUC),检验列线图模型对HER-2阳性乳腺癌患者预后的预测价值。结果观察组患者的总有效率高于对照组(86.4%比69.6%,χ^(2)=10.280,P=0.001)。2组患者化疗期间的不良反应发生率比较,差异无统计学意义(P均>0.050)。中位随访24个月,观察组PFS为20.0(18.0,21.0)个月,长于对照组的17.0(16.0,19.0)个月(Z=16.673,P<0.001)。建模组175例患者中有39例(22.3%)预后不良,验证组75例患者中16例(21.3%)预后不良,2组患者的预后差异无统计学意义(χ^(2)=0.028,P=0.868)。多因素分析显示内脏转移(HR=2.684,95%CI:1.056~6.821,P=0.038)、Ki-67阳性(HR=8.209,95%CI:3.048~22.106,P<0.001)、临床Ⅲ期(HR=4.038,95%CI:1.865~8.744,P<0.001)、TNF-α高表达(HR=7.433,95%CI:3.370~16.396,P<0.001)、IL-6高表达(HR=1.066,95%CI:1.004~1.131,P=0.036)和IL-8高表达(HR=1.735,95%CI:1.251~2.406,P=0.001)是HER-2阳性乳腺癌患者预后的危险因素。建模组、验证组的C-index值分别为0.938和0.946,2组的校正曲线均与理想曲线拟合反应良好。建模组AUC为0.936(95%CI:0.879~0.993,P<0.001),验证组AUC为0.944(95%CI:0.872~0.988,P<0.001)。结论吡咯替尼能有效提高HER-2阳性乳腺癌患者的临床治疗疗效,本研究的预后预测模型可筛选出需要进一步强化辅助治疗的HER-2阳性乳腺癌患者。
Objective To analyze the efficacy of pyrotinib in the patients with HER-2-positive breast cancer and identify risk factors associated with poor prognosis.Methods A retrospective cohort study was conducted,involving 250 HER-2-positive breast cancer patients in the People’s Hospital of Yuechi County,Sichuan Province from May 2020 to May 2023.Among them,125 patients receiving pyrotinib combined with conventional chemotherapy served as the observation group,and 125 patients undergoing conventional chemotherapy served as the control group.The chemotherapy efficacy and adverse reaction rates between the two groups were compared using χ^(2) test.Progression-free survival(PFS)was analyzed using the Kaplan-Meier method,with log-rank tests used for intergroup PFS comparisons.Cox proportional hazards models were used for multivariate analysis of potential risk factors of poor prognosis.Patients were randomly divided into a modeling group and a validation group(7∶3 ratio)using simple random sampling.The R 4.1.0 software with the rms package was utilized to establish a prognostic prediction model for HER-2-positive breast cancer.Bootstrap validation was performed to calculate the concordance index(C-index).Receiver operating characteristic(ROC)curves were plotted,and the area under the curve(AUC)was computed to evaluate the predictive value of the nomogram model.Results The overall response rate was significantly higher in the observation group than in the control group(86.4%vs 69.6%,χ^(2)=10.280,P=0.001).No significant difference was found in the incidence of adverse reactions between two groups(all P>0.050).After a median follow-up of 24 months,the PFS was significantly longer in the observation group than in the control group[20.0(18.0,21.0)months vs 17.0(16.0,19.0)months,Z=16.673,P<0.001].Among the 175 patients in the modeling group,39(22.3%)had poor prognosis,while 16 out of 75 patients(21.3%)in the validation group experienced poor prognosis,with no significant intergroup difference(χ^(2)=0.028,P=0.868).Multivariate analyses identified visceral metastasis(HR=2.684,95%CI:1.056-6.821,P=0.038),Ki-67 positivity(HR=8.209,95%CI:3.048-22.106,P<0.001),clinical stage Ⅲ(HR=4.038,95%CI:1.865-8.744,P<0.001),and elevated expression of TNF-α(HR=7.433,95%CI:3.370-16.396,P<0.001),IL-6(HR=1.066,95%CI:1.004-1.131,P=0.036)and IL-8(HR=1.735,95%CI:1.251-2.406,P=0.001)as independent risk factors for poor prognosis.The C-index values were 0.938 and 0.946 in the modeling and validation group,respectively,with calibration curves closely aligned to the ideal curve.The modeling group achieved an AUC of 0.936(95%CI:0.879-0.993,P<0.001),while the validation group showed an AUC of 0.944(95%CI:0.872-0.988,P<0.001).Conclusion Pyrotinib significantly improves therapeutic efficacy in patients with HER-2-positive breast cancer.The prognostic prediction model developed in this study can identify patients requiring intensified adjuvant therapy.
作者
郑仁英
罗凤梅
李婷婷
金勇
万小亚
Zheng Renying;Luo Fengmei;Li Tingting;Jin Yong;Wan Xiaoya(Department of Oncology,People’s Hospital of Yuechi County,Yuechi 638300,Sichuan Province,China)
出处
《中华乳腺病杂志(电子版)》
2025年第3期167-174,共8页
Chinese Journal of Breast Disease(Electronic Edition)
基金
2021年四川青年创新科研资助课题(Q21034)。
作者简介
通信作者:金勇,Email:3234523@qq.com。
