Cardiotoxicity with adjuvant trastuzumab use in breast cancer: A single institution's experience

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.