title: Cardiotoxicity and Cardiac Monitoring During Adjuvant Trastuzumab in Daily Dutch Practice: A Study of the Southeast Netherlands Breast Cancer Consortium.
abstract: 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 breast cancer.
  
  
  
  We included all patients with stage I-III breast cancer 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 of cardiotoxicity in patients treated with adjuvant trastuzumab, using similar cardiac endpoints as in the Herceptin Adjuvant (HERA) trial.
  
  
  
  Of 2,684 included patients, 476 (17.7%) had a HER2-positive 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, defined as a drop in LVEF of at least 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.
  
  
  
  In the first years after implementation of trastuzumab for treatment of early breast cancer, physicians frequently based their decision to discontinue treatment on patient symptoms apart from LVEF outcome. We suggest that focusing LVEF monitoring on the first 6 months might be more cost-effective without compromising patient safety. Nonetheless, further research is needed.
  
  
  
  Knowledge of when cardiotoxicity occurs in daily practice will help shape the best follow-up method for cardiac monitoring in trastuzumab-treated patients with human epidermal growth receptor 2-positive early breast cancer. In the first years after implementation of trastuzumab for treatment of early breast cancer, physicians frequently based their decision to discontinue treatment on patient symptoms apart from left ventricular ejection fraction (LVEF) outcome. When cardiotoxicity was found in daily practice, it occurred mainly in the first 6 months after start of trastuzumab. This study suggests that focusing LVEF monitoring on the first 6 months might be more cost-effective without compromising patient safety. This insight stresses the relevance of performing real-world analyses.
authors.affiliation: Department of Medical Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Shanly C
authors.initials: SC
authors.lastname: Seferina
authors.affiliation: Department of Medical Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Maaike
authors.initials: M
authors.lastname: de Boer
authors.affiliation: Department of Internal Medicine, Máxima Medical Centre, Veldhoven, The Netherlands.
authors.forename: M Wouter
authors.initials: MW
authors.lastname: Derksen
authors.affiliation: Department of Internal Medicine, Atrium Medical Centre Parkstad, Heerlen, The Netherlands.
authors.forename: Franchette
authors.initials: F
authors.lastname: van den Berkmortel
authors.affiliation: Department of Medical Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands Department of Internal Medicine, Orbis Medical Centre, Sittard, The Netherlands.
authors.forename: Roel J W
authors.initials: RJ
authors.lastname: van Kampen
authors.affiliation: Department of Internal Medicine, VieCuri Medical Centre, Venlo, The Netherlands.
authors.forename: Agnès J
authors.initials: AJ
authors.lastname: van de Wouw
authors.affiliation: GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Manuela
authors.initials: M
authors.lastname: Joore
authors.affiliation: Department of Medical Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands Radboud Institute for Health Science, Nijmegen, The Netherlands.
authors.forename: Petronella G M
authors.initials: PG
authors.lastname: Peer
authors.affiliation: Department of Medical Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands Department of Epidemiology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Adri C
authors.initials: AC
authors.lastname: Voogd
authors.affiliation: Department of Medical Oncology, Maastricht University Medical Centre, Maastricht, The Netherlands GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands vcg.tjan.heijnen@mumc.nl.
authors.forename: Vivianne C G
authors.initials: VC
authors.lastname: Tjan-Heijnen
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D066126:Cardiotoxicity / Q000453:epidemiology*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors*; D000068878:Trastuzumab / Q000009:adverse effects*; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Adjuvant trastuzumab; Cardiac monitoring; Cardiotoxicity; Daily practice