PTEN缺失与HER2阳性晚期乳腺癌曲妥珠单抗耐药后拉帕替尼治疗疗效分析

PTEN loss correlates with the clinical efficacy of lapatinib in HER2 positive metastatic breast cancer with trastuzumab-resistance

目的 观察PTEN、p-4EBP1的状态及临床特征与人表皮生长因子受体2（HER2）阳性晚期乳腺癌患者曲妥珠单抗耐药后二线抗HER2药物拉帕替尼疗效的相关性.方法 回顾分析军事医学科学院附属医院乳腺肿瘤中心60例拉帕替尼联合卡培他滨治疗的HER2阳性晚期乳腺癌患者的临床疗效,采用免疫组化方法对患者拉帕替尼疗前转移病灶组织标本进行PTEN及p-4EBP1状态的检测,分析PTEN、p-4EBP1的状态及临床特征与疗效的相关性.结果 该组患者中位无进展生存期（PFS）为4.6个月,ORR、CBR分别为36.7％、50.0％.单因素分析显示：PTEN缺失（P=0.015）、肝转移（P=0.02）患者的中位PFS较短.多因素分析显示：PTEN缺失、肝转移是患者独立的不良预后因素（P值分别为0.005,0.006）.结论 HER2阳性晚期乳腺癌曲妥珠单抗耐药后能从新靶向药物拉帕替尼治疗中获益,PTEN状态及肝转移能够预测后续拉帕替尼治疗的疗效.相关分子指标的检测能为优化HER2阳性乳腺癌的个体化治疗提供参考.

Objective To discuss the indexes related to the efficacy of lapatinib after failure in trastuzumab in HER2-positive metastatic breast cancer （MBC） such as the status of PTEN,p-4EBP1 and clinical features.Methods Sixtymatched patients were included.Immunohistochemical （IHC） test of tissue specimens of metastatic lesions were applied to determine the status of PTEN and p-4EBP1.The correlation betweenclinical efficacy andthestatus of PTEN,p-4EBP1 and clinical features were analysed by long-rank test and Cox regression.Results In all patients,themedian progression free survival （PFS）,ORR and CBR was 4.6 months,36.7％ and 50.0％ respectively.Univariate analysis revealed that lapatinibtreated patients with PTEN loss （P =0.015） and liver metastasis （P =0.02） had significantly shorter median PFS.Multivariate analysis revealed that patients with PTEN lossandliver metastasis had higher risk of diseaseprogression （P =0.005,0.006,respectively）.Conclusion HER2-positive MBC with trastuzumab-resistance could benefit from lapatinib regimen.PTEN statusand liver metastasis couldpredict theclinical efficacyof subsequent lapatinib therapy.The detection ofrelated biomarkers could provide some referenceto optimize the personal treatment with HER2-positive breast cancer.