PURPOSE: Trastuzumab is an important biologic agent with significant activity in 
breast cancers that overexpress the HER2/neu marker. However, trastuzumab is 
associated with cardiotoxicity that has not yet been fully explored. We present 
our experience with patients who developed trastuzumab-related cardiotoxicity.
PATIENTS AND METHODS: Over a 4-year period, 38 patients with HER2/neu-positive 
breast cancer were referred for suspected trastuzumab-related cardiotoxicity. 
All patients had previously received anthracycline-based chemotherapy. Results 
After doxorubicin but before trastuzumab, the mean (+/- standard deviation) left 
ventricular ejection fraction (LVEF) was 0.61 +/- 0.13, and the LVEF decreased 
to 0.43 +/- 0.16 after trastuzumab (P < .0001). After withdrawal of trastuzumab, 
the LVEF increased to 0.56 +/- 0.11. Mean time to recovery of LVEF was 1.5 
months and was temporally associated with medical treatment in 32 (84%) of the 
38 patients but occurred without treatment in six patients (16%). Increases in 
LVEF were noted in 37 of the 38 patients. Twenty-five of these patients were 
re-treated with trastuzumab; three patients had recurrent left ventricular 
dysfunction, but 22 patients (88%) did not. All re-treatment patients continued 
on their therapeutic regimen for heart failure when rechallenged with 
trastuzumab. Nine patients underwent endomyocardial biopsy. Ultrastructural 
changes were not seen.
CONCLUSION: Patients who develop cardiotoxicity while receiving trastuzumab 
therapy generally improve on removal of the agent. The mechanism of 
trastuzumab-related cardiac dysfunction is different from that of anthracycline 
cardiotoxicity, in part, demonstrated by the absence of anthracycline-like 
ultrastructural changes. Reintroducing trastuzumab may be appropriate for some 
individuals who previously have experienced trastuzumab-related cardiac 
dysfunction.