Cardiotoxicity and Cardiac Monitoring During Adjuvant Trastuzumab in Daily Dutch Practice: A Study of the Southeast Netherlands Breast Cancer Consortium

Introduction. We assessed the incidence and timing of first cardiac events, impact on trastuzumab prescription, and role of left ventricular ejection fraction (LVEF) monitoring in daily practice of trastuzumab-treated patients with human epidermal growth receptor 2 (HER2)-positive early breastcancer.
Methods. We included all patients with stageI–III breastcancer diagnosed in the early years(2005–2007)after the introduction of adjuvant trastuzumab in five hospitals in Southeast Netherlands.We studied the incidence and timing ofcardiotoxicity in patients treated with adjuvant trastuzumab, using similar cardiac endpointsasintheHerceptinAdjuvant(HERA)trial.
Results. Of 2,684 included patients, 476 (17.7%) had a HER2positive tumor. Of these, 269 (56.9%) were treated with adjuvant chemotherapy, and of these, 230 (85.5%) also received trastuzumab. Cardiotoxicity was observed in 29 of 230 patients (12.6%).Twenty of the 230 patients (8.7%) had symptomatic cardiotoxicity definedasadropinLVEFofatleast 10 percentage points and to below 50%, accompanied by symptoms of congestive heart failure. Trastuzumab was definitely discontinued because of supposed cardiotoxicity in 36 patients (15.6%), of whom only 15 (6.5%) had a significant LVEF drop. Of the 36 patients who prematurely discontinued trastuzumab (including the 29 in whom cardiotoxicity was observed), 84.8% stopped in the first 6 months. No cardiac deaths were seen.
Conclusion. In the first years after implementation of trastuzumab for treatment of early breastcancer,physiciansfrequently based their decision to discontinue treatment on patient symptomsapartfromLVEFoutcome.Wesuggestthatfocusing LVEF monitoring on the first 6 months might be more costeffective without compromising patient safety. Nonetheless further research is needed.