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111Indium-trastuzumab visualises myocardial human epidermal growth factor receptor 2 expression shortly after anthracycline treatment but not during heart failure: A clue to uncover the mechanisms of trastuzumab-related cardiotoxicity

2007; Elsevier BV; Volume: 43; Issue: 14 Linguagem: Inglês

10.1016/j.ejca.2007.06.024

1879-0852

M.A. de Korte, Elisabeth G.E. de Vries, Marjolijn N. Lub–de Hooge, P.L. Jager, Jourik A. Gietema, Winette T.A. van der Graaf, W.J. Sluiter, D.J. van Veldhuisen, Thomas M. Suter, Dirk Th. Sleijfer, Patrick J. Perik,

Chemotherapy-induced cardiotoxicity and mitigation

Abstract Aim Trastuzumab can induce cardiotoxicity, particularly when combined with anthracyclines. Myocardial human epidermal growth factor receptor 2 (HER2) expression may be transiently upregulated by a compensatory mechanism following cardiac stress. 111 In-DTPA-trastuzumab, scintigraphy can detect HER2 positive tumour lesions, however previously, we found myocardial uptake in only 1 of the 15 anthracycline-pre-treated patients with a median of 11 months after the last anthracycline administration. To evaluate whether myocardial HER2 expression is upregulated by anthracycline-induced cardiac stress or in case of heart failure by chronic pressure or volume overload, we performed 111 In-DTPA-trastuzumab scans in patients shortly after anthracyclines and with non-anthracycline-related heart failure. Methods Patients within 3 weeks after undergoing 4–6 cycles first-line anthracycline-based chemotherapy and patients with heart failure due to cardiac disease underwent gammacamera imaging 48 and 96h after 111 In-DTPA-trastuzumab intravenously. Results Myocardial 111 In-DTPA-trastuzumab uptake was observed in 5 out of 10 anthracycline-treated patients, who all were without symptomatic cardiac dysfunction. None of the 10 heart failure patients showed myocardial uptake. Conclusion Shortly after completion of anthracycline treatment, myocardial HER2 over-expression was detectable in 50% of the patients. 111 In-DTPA-trastuzumab scintigraphy after anthracyclines prior to adjuvant trastuzumab potentially identifies patients susceptible for trastuzumab-related cardiotoxicity and thus may facilitate the optimal timing of trastuzumab therapy.