Aldiab Abdurrahman
King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
J Saudi Heart Assoc. 2010 Jul;22(3):133-6. doi: 10.1016/j.jsha.2010.04.009. Epub 2010 May 11.
Trastuzumab use in Her-2-neu positive breast cancer patients is the current standard of care. Trastuzumab is known to result in cardiotoxicity. The toxicity seems to be dose-dependent, and serial cardiology assessment with echocardiography is advised. In spite of this, patients do develop cardiotoxicity and identification of patients at high risk and, if possible, any preventive means is of paramount importance.
We performed a retrospective analysis of medical records of all breast cancer patients presenting at King Khalid University Hospital from 02/2006 to 06/2009 and receiving adjuvant trastuzumab on the basis of either immunohistochemistry showing Her-2-neu (3+) or FISH positive Her-2-neu receptor status. Patients received adjuvant trastuzumab at an 8 mg/kg loading dose over 90 min, followed by 6 mg/kg every 3 weeks. A repeat multigated acquisition scan/echocardiogram was done after every 4 courses. Patient characteristics, such as age, menopausal status, tumor size, lymph nodal status, distant metastasis at presentation, grade of tumor, estrogen and progesterone receptor status, comorbid conditions (diabetes, hypertension, ischemic heart diseases), chemotherapy received, total dose of trastuzumab, timing of cardiotoxicity, and number of patients having cardiotoxicity, were recorded. A patient was said to have cardiotoxicity if the ejection fraction dropped by 10% of the original value or if there was a drop in the ejection fraction below the normal value.
A total number of 98 breast cancer patient records were analyzed in this study. A total of 11 patients developed cardiotoxicity, evident by a drop in the ejection fraction on an echocardiogram. Seven patients out of 11 had a drop in ejection fraction below 10% of the baseline value, and 4 patients out of 11 had a drop in ejection fraction below normal values. A total of 5 patients became symptomatic with dyspnea on exertion, with 2 being of NYC Class I, 2 being of NYC Class II, 1 being of NYC Class III, and none being of NYC Class IV. Seven patients out of 11 with cardiotoxicity had diabetes and hypertension as comorbid conditions. Patients receiving doxorubicin in neoadjuvant and adjuvant settings were associated with cardiotoxicity. The total dose of trastuzumab had a strong association, with the patient getting more than 60 mg/kg in a 3-weekly fashion being associated with cardiotoxicity.
Trastuzumab is associated with significant cardiotoxicity. Asymptomatic and symptomatic cardiotoxicity and toxicity seem to be dose-dependent in an adjuvant setting. At the end of therapy, more frequent than usual monitoring of cardiac function is suggested to prevent this toxicity.
在人表皮生长因子受体2（Her-2-neu）阳性乳腺癌患者中使用曲妥珠单抗是当前的标准治疗方法。已知曲妥珠单抗会导致心脏毒性。这种毒性似乎与剂量有关，建议通过超声心动图进行系列心脏评估。尽管如此，患者仍会出现心脏毒性，识别高危患者并尽可能采取任何预防措施至关重要。
我们对2006年2月至2009年6月在哈立德国王大学医院就诊并接受辅助曲妥珠单抗治疗的所有乳腺癌患者的病历进行了回顾性分析，这些患者基于免疫组化显示Her-2-neu（3+）或荧光原位杂交（FISH）检测Her-2-neu受体状态为阳性。患者接受90分钟静脉滴注8mg/kg的曲妥珠单抗负荷剂量，随后每3周给予6mg/kg。每4个疗程后进行一次重复门控心血池扫描/超声心动图检查。记录患者的特征，如年龄、绝经状态、肿瘤大小、淋巴结状态、就诊时远处转移情况、肿瘤分级、雌激素和孕激素受体状态、合并症（糖尿病、高血压、缺血性心脏病）、接受的化疗、曲妥珠单抗的总剂量、心脏毒性发生时间以及发生心脏毒性的患者数量。如果射血分数下降至原始值的10%或射血分数降至正常值以下，则认为该患者发生了心脏毒性。
本研究共分析了98例乳腺癌患者的病历。共有11例患者发生了心脏毒性，超声心动图显示射血分数下降。11例患者中有7例射血分数下降至基线值的10%以下，11例患者中有4例射血分数下降至正常值以下。共有5例患者出现劳力性呼吸困难症状，其中纽约心脏协会（NYC）心功能分级I级2例，II级2例，III级1例，IV级无。11例发生心脏毒性的患者中有7例合并糖尿病和高血压。在新辅助和辅助治疗中接受多柔比星的患者与心脏毒性相关。曲妥珠单抗的总剂量与心脏毒性有很强的相关性，每3周接受超过60mg/kg曲妥珠单抗的患者与心脏毒性相关。
曲妥珠单抗与显著的心脏毒性相关。在辅助治疗中，无症状和有症状的心脏毒性似乎都与剂量有关。在治疗结束时，建议比平时更频繁地监测心脏功能以预防这种毒性。
