Publication Year: 2000 Visited: 74

393

HER2-Expression in the Myocardium as a Cause for the Cardiotoxicity of Trastuzumab (Herceptin)? Ilka Fuchs, Solveyg Landt, Helmut Buehler, Katja Evers, Uwe Kuehl, Anke Kleine-Tebbe, Frank Schaeper, Sylvia Coupland, Werner Lichtenegger, Gerhard Schaller, Charité Campus Virchow Humboldt Univ, Berlin, Germany; Free Univ, Berlin, Germany.

The combination of the FDA approved HER2-antibody trastuzumab (Herceptin) with anthracyclines in the therapy of metastatic breast cancer proofed to be very effective, but this regimen is limited by a dramatic increase in cardiotoxicity. Since HER2 plays an essential role in embryonic cardiogenesis as well as in cardiac hypertrophy, a putative interaction of trastuzumab with HER2-expressing myocardial cells is an interesting hypothesis. Therefore we investigated myocardial tissue to clarify whether or not HER2 is upregulated. Heart biopsies of 33 patients with decreased left ventricular function of the heart were obtained. The histological alterations ranged from acute and chronic myocarditis to different degrees of myocardial hypertrophy. Heart tissue of 15 patients with the history of anthracycline therapy for breast cancer as well as myocardium of 10 breast cancer patients without anthracycline treatment was also assessed. HER2 expression was analyzed immunhistochemically using the HercepTest or the primary antibody A 0485 of DAKO´s. HER2 gene amplification was analyzed by fluorescence in situ hybridzation (FISH) using the Inform-Kit of Ventana. In all specimen, 2 copies of the HER2 gene could be detected. Only in a few biopsies a light, discontinuous membrane staining was notable. None of the specimens showed an overexpression or gene amplification of HER2. Therefore, we conclude that pathological alterations of the heart do not necessarily lead to an overexpression or gene amplification of HER2 in the myocardium. On the other hand we can presently not assess the relevance of low HER2 expression levels to the cardiotoxic effects of trastuzumab.