Factors Predicting Trastuzumab-related Cardiotoxicity in a Real-world Population of Women with HER2+ Breast Cancer

BACKGROUND: Trastuzumab may improve disease-free survival after chemotherapy for HER2-positive breast cancer. However, it carries a risk of cardiotoxicity and counseling patients about such risks is part of informed consent. The National Institute for Health and Clinical Excellence has published guidelines for cardiac assessment before and during treatment with trastuzumab in order to minimize the risk of cardiotoxicity. The aim of the present study was to identify risk factors for cardiotoxicity attributed to trastuzumab in a cohort population treated for primary and metastatic breast cancer. PATIENTS AND METHODS: This study included all women who started a course of trastuzumab from February 2006 - February 2011 at three NHS Trusts in the UK. Their cardiac function during treatment was recorded and cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF) ≥ 10% and a reduction to <50%, or a clinical reduction in cardiac function as defined by the New York Heart Association. An independent samples t-test was used to assess whether patient age predicted cardiotoxicity. Pearson's chi-squared tests of independence were used to investigate the association between cardiotoxicity, the indication for trastuzumab, exposure to anthracycline chemotherapy, and Adult Comorbidity Evaluation-27 index (ACE-27) scores. RESULTS: There were 388 female patients included in this study, with a mean age of 54 (range = 25-100 years). Cardiotoxicity was recorded during 61 (15.72%) courses of trastuzumab treatment. There were no associations between cardiotoxicity and the three factors (indication, exposure to anthracyclines, or ACE-27 score), and no significant difference in age between patients with and those without cardiotoxicity. However, subgroup analysis of patients who experienced cardiotoxicity (n = 61) showed that there was a negative correlation (-0.455; p = 0.001) between time-to-first cardiotoxicity event and age in the group who had received concurrent anthracycline therapy (n=49). CONCLUSION: In a real-world 5-year population of patients who received trastuzumab, the incidence of drug-related cardiotoxicity was higher than expected, and the age of the patients appeared to predict the first cardiotoxic event amongst those who experienced cardiotoxicity and had received prior anthracyclines. However, incidence of cardiotoxicity in the whole cohort did not appear to be predicted by age, comorbidity, indication, or exposure to anthracylines. Vigilance, therefore, seems justified when conducting cardiac surveillance for all patients during treatment with trastuzumab, but especially for those who are elderly and receiving concurrent anthracycline therapy.