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Annals of Oncology Advance Access published online on May 13, 2008
Annals of Oncology, doi:10.1093/annonc/mdn292
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

review

Anthracycline–trastuzumab regimens for HER2/neu-overexpressing breast cancer: current experience and future strategies

D. Rayson1,*, D. Richel2, S. Chia3, C. Jackisch4, S. van der Vegt5 and T. Suter6

1 Department of Medical Oncology, Dalhousie University, Halifax, Nova Scotia, Canada
2 Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands
3 Department of Medical Oncology, British Columbia Cancer Agency, Vancouver Cancer Centre, Vancouver, BC, Canada
4 Department of Obstetrics and Gynecology and Breast Center, Klinikum Offenbach, Offenbach, Germany
5 Department of Oncology, Mesos Medical Centre, Utrecht, The Netherlands
6 Swiss Cardiovascular Center, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland

* Correspondence to: Dr D. Rayson, Dalhousie University, Halifax, Nova Scotia, Canada. Tel: +1-902-473-6106; Fax: +1-902-473-6186; E-mail: daniel.rayson{at}cdha.nshealth.ca

Anthracycline–trastuzumab-containing regimens demonstrate significant clinical activity in human epidermal growth factor receptor 2 (HER2)-positive breast cancer; however, the utility of this strategy is limited by unacceptably high rates of significant cardiotoxicity, particularly with concurrent administration. Anthracycline-induced cardiotoxicity is thought to be mediated primarily through increased myocardial oxidative stress, modified partly by the activity of neuregulins. Trastuzumab-induced cardiotoxicity is thought to be mediated by the ErbB/neuregulin system, with exposure to trastuzumab partly blocking the protective effect of neuregulins on the myocardium. As a result, trastuzumab increases the risk of anthracycline-induced cardiotoxicity. Several strategies have been adopted in attempts to minimize cardiotoxicity, including patient selection on the basis of preexisting cardiac risk, monitoring of cardiac function during treatment, and early management of cardiac dysfunction. The use of less cardiotoxic anthracyclines may be one strategy to lessen the risk of cardiotoxicity. Liposomal doxorubicin products offer similar efficacy compared with conventional doxorubicin, with significantly less cardiotoxicity, and have been successfully used in combination with trastuzumab in the metastatic and neo-adjuvant setting. Clinical trials are currently underway to assess the safety of pegylated liposomal doxorubicin during concurrent administration with trastuzumab compared with standard sequential treatment using conventional doxorubicin in the adjuvant setting.

adjuvant therapy, anthracyclines, breast cancer, cardiotoxicity, HER2+, pegylated liposomal doxorubicin, trastuzumab

Received for publication February 21, 2008. Revision received April 11, 2008. Accepted for publication April 14, 2008.


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