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在阿曼三级保健中心,曲妥珠单抗在人表皮生长因子受体 2 阳性乳腺癌患者中的心脏毒性。

Trastuzumab cardiotoxicity in HER2-positive breast cancer patients in tertiary health care center, sultanate of Oman.

机构信息

Pharmacy Department, Sultan Qaboos University Hospital, Seeb, Oman.

School of Pharmacy, Queens University, Belfast, Northern Ireland.

出版信息

J Oncol Pharm Pract. 2021 Mar;27(2):312-321. doi: 10.1177/1078155220919888. Epub 2020 Apr 27.

Abstract

Trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2), is used to treat breast cancers harboring amplification of the HER2 locus. Cardiotoxicity is a common side effect of trastuzumab that leads to discontinuation of treatment in a significant proportion of cancer patients. In our retrospective study, we evaluate the prevalence and identify the risk factors for cardiotoxicity associated with trastuzumab in HER2-positive breast cancer patients attending to Sultan Qaboos University Hospital between 10/2012 and 10/2017. Using patient records, we collected patients' characteristics (age, menopausal status, lymph nodal status, distant metastasis at presentation, grade of tumor, comorbidities (diabetes mellitus, hypertension, coronary artery disease diseases)), chemotherapy received and total dose of trastuzumab as well as cardiotoxicity (including timing). Cardiotoxicity was defined based on the ejection fraction dropping by 10% of the original value or a drop in the ejection fraction below the normal value. Among the 146 patients included in the study, 35 showed trastuzumab-induced cardiotoxicity (24%). Twenty-nine (83%) of those patients stopped trastuzumab temporarily. Risk of trastuzumab-induced cardiotoxicity was not altered by common cardiac risk factors such as history of coronary artery disease, hypertension and diabetes. Previous anthracyclines therapy exposure increased the risk of trastuzumab-induced cardiotoxicity significantly (=0.009). None of the other covariates influenced the incidence of trastuzumab-induced cardiotoxicity, which may be related to the relatively small sample size. Further studies are warranted to establish ways to predict, prevent, and treat trastuzumab-induced cardiotoxicity to provide patients with maximal therapeutic benefit.

摘要

曲妥珠单抗是一种针对人表皮生长因子受体 2(HER2)的单克隆抗体,用于治疗 HER2 基因座扩增的乳腺癌。曲妥珠单抗的心脏毒性是一种常见的副作用,导致相当一部分癌症患者停止治疗。在我们的回顾性研究中,我们评估了在 2012 年 10 月至 2017 年 10 月期间在苏丹卡布斯大学医院就诊的 HER2 阳性乳腺癌患者中,与曲妥珠单抗相关的心脏毒性的患病率,并确定了其危险因素。我们使用患者记录收集了患者的特征(年龄、绝经状态、淋巴结状态、初诊时的远处转移、肿瘤分级、合并症(糖尿病、高血压、冠心病))、接受的化疗和曲妥珠单抗的总剂量以及心脏毒性(包括时间)。心脏毒性的定义是射血分数比原始值下降 10%或射血分数下降到正常值以下。在纳入研究的 146 名患者中,有 35 名出现曲妥珠单抗诱导的心脏毒性(24%)。其中 29 名(83%)患者暂时停止了曲妥珠单抗治疗。冠心病、高血压和糖尿病等常见心脏危险因素并未改变曲妥珠单抗诱导的心脏毒性的风险。先前接受蒽环类药物治疗显著增加了曲妥珠单抗诱导的心脏毒性的风险(=0.009)。其他协变量均未影响曲妥珠单抗诱导的心脏毒性的发生率,这可能与样本量较小有关。需要进一步研究以确定预测、预防和治疗曲妥珠单抗诱导的心脏毒性的方法,为患者提供最大的治疗效益。

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