HER2 in Brain Metastases: Issues of Concordance, Survival, and Treatment

Abstract

To the Editor: We read with interest the article by Seidman et al 1 describing the risks of adverse cardiac events associated with trastuzumab therapy for metastatic breast cancer, published in the March 1, 2002, issue of the Journal of Clinical Oncology. In that retrospective review of records from 1,219 patients enrolled onto one of seven phase II or III clinical trials, the risk of adverse cardiac events was low (3% to 7%) when trastuzumab was prescribed alone. In contrast, the risk was higher when trastuzumab was combined with paclitaxel (13%) and inordinately high when it was combined with anthracyclines and cyclophosphamide (26%).From pathophysiologic and clinical perspectives, several aspects of this cardiotoxicity remain unclear. 2,3 For instance, data from clinical studies do not clarify whether cardiotoxicity develops early or whether it is related to a cumulative dose of treatment, as has been observed with anthracyclines. Likewise, the clinical course of the cardiomyopathic disorder after discontinuation of treatment has not been described.Since March 2001, we have followed prospectively 28 consecutive patients treated for metastatic breast cancer with trastuzumab, administered in an initial dose of 4 mg/m 2 followed by 2 mg/m 2 weekly, and paclitaxel, in a dose of 80 mg/m 2 , 6 out of 8 weeks. Surveillance of the cardiac status was by way of echocardiography, systematically performed at weekly intervals during the first month and then every 2 months by the same techniques and same operator, to ensure reproducibility of the measurements. The criterion threshold for detection of cardiotoxicity was a more than 10% decrease in left ventricular ejection fraction between two consecutive examinations. The 28 patients (mean age, 54 years; range, 40 to 70 years) had received an anthracycline, including doxorubicin in five patients, epirubicin in 11 patients, or mitoxantrone in 12 patients, as adjunctive therapy before being placed on the trastuzumab-paclitaxel combination. A more than 10% decrease in left ventricular ejection fraction was observed in four patients (14%), similar to the 13% incidence of adverse cardiac effects reported by Seidman et al. 1 In all cases, this decrease in left ventricular function appeared unexpectedly early. It was observed immediately after the first inductive course of therapy in two patients, after 2 weeks of treatment in one patient, and after 4 weeks in one patient. No progression of ventricular dysfunction was observed after withdrawal of therapy. Echocardiographic measurements have remained unchanged in two patients and have normalized within 4 months in the others. During long-term follow-up of the other 24 patients, including a mean number of courses of therapy of 20 (range, 12 to 54 courses), no evidence of cardiotoxicity was observed.This observation of very early, non-dose-dependent cardiotoxicity suggests the development of an acute inflammatory reaction resembling acute myocarditis. Like myocarditis, the disorder may resolve without sequelae, or evolve toward chron...

Risk factors for brain relapse in HER2-positive metastatic breast cancer patients

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Extended trastuzumab therapy improves the survival of HER2-positive breast cancer patients following surgery and radiotherapy for brain metastases

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Radiotherapy in Lung Adenocarcinoma with Brain Metastases: Effects of Activating Epidermal Growth Factor Receptor Mutations on Clinical Response

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