HER2 Support Group Forums - View Single Post - Scientist discovering mechanism of herceptin cardiotoxicity

Lani · 07-15-2006, 05:20 AM

1: J Clin Oncol. 2005 Nov 1;23(31):7820-6. Links

Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment.

Ewer MS, Vooletich MT, Durand JB, Woods ML, Davis JR, Valero V, Lenihan DJ.

Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, 77030, USA. mewer@mdanderson.org

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.

PMID: 16258084 [PubMed - indexed for MEDLINE]

"ultrastructural changes" refers to findings such as changes in subcellular organelles ( including abnormal appearance of mitochondria)

07-15-2006, 05:20 AM	#6
Lani Senior Member Join Date: Mar 2006 Posts: 4,782	Here is a study where some patients agreed to cardiac biopsy! 1: J Clin Oncol. 2005 Nov 1;23(31):7820-6. Links Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. Ewer MS, Vooletich MT, Durand JB, Woods ML, Davis JR, Valero V, Lenihan DJ. Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, 77030, USA. mewer@mdanderson.org 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. PMID: 16258084 [PubMed - indexed for MEDLINE] "ultrastructural changes" refers to findings such as changes in subcellular organelles ( including abnormal appearance of mitochondria)