Author + information
- Received June 24, 2018
- Revision received September 5, 2018
- Accepted September 19, 2018
- Published online February 25, 2019.
- Ann Banke, MDa,b,∗ (, )
- Emil L. Fosbøl, MD, PhDc,
- Marianne Ewertz, Professor, MD, DMscb,d,
- Lars Videbæk, MD, PhDa,
- Jordi S. Dahl, MD, PhDa,b,
- Mikael Kjær Poulsen, MD, PhDa,
- Søren Cold, MD, PhDd,
- Maj-Britt Jensen, CandSciente,
- Gunnar H. Gislason, MD, PhDf,g,
- Morten Schou, MD, PhDh,∗ and
- Jacob E. Møller, MD, DMScia,b,∗
- aDepartment of Cardiology, Odense University Hospital, Odense, Denmark
- bInstitute of Clinical Research, University of Southern Denmark, Odense, Denmark
- cDepartment of Cardiology, Rigshospitalet, Copenhagen, Denmark
- dDepartment of Oncology, Odense University Hospital, Odense, Denmark
- eDanish Breast Cancer Cooperative Group, Rigshospitalet, Copenhagen, Denmark
- fDepartment of Cardiology, Copenhagen University, Herlev and Gentofte Hospital, Hellerup, Denmark
- gDanish Heart Foundation, Copenhagen, Denmark
- hDepartment of Cardiology, Copenhagen University, Herlev and Gentofte Hospital, Herlev, Denmark
- ↵∗Address for correspondence:
Dr. Ann Banke, Department of Cardiology, Odense University Hospital, J.B. Winsløws Vej 4, 5000 Odense, Denmark.
Objectives This study sought to evaluate the long-term risk of developing heart failure (HF) in patients receiving trastuzumab therapy.
Background Trastuzumab has improved the prognosis in patients with HER2-positive breast cancer, but it can induce left ventricular dysfunction with reduced ejection fraction or HF during treatment. The long-term risk of HF is less well described.
Methods In a nationwide Danish retrospective cohort study, 9,901 patients scheduled for adjuvant treatment for early-stage breast cancer were identified in the Danish Breast Cancer Cooperative Group database. Of these, 8,812 patients (25% HER2-positive; 51.7 ± 8.5 years of age) received chemotherapy including anthracycline; and if they were HER2 positive, trastuzumab was added. The primary endpoint was a diagnosis of HF assessed before and after 18 months in a landmark analysis to distinguish short- and long-term risks.
Results Median follow-up was 5.4 years (interquartile range [IQR]: 4.1 to 6.8 years). In the trastuzumab group, 60 patients had HF by 9 years versus 51 in the group who were treated with chemotherapy alone, corresponding to incidence rates per 1,000 patient years of 5.3 (95% confidence interval [CI]: 4.1 to 6.8) versus 1.4 (95% CI: 1.1 to 1.8), respectively. The cumulative incidence of HF was higher in the trastuzumab group at both the short- and long-term (p < 0.01), yielding adjusted hazard ratios of 8.7 (95% CI: 4.6 to 16.5; p < 0.01) for early HF and 1.9 (95% CI: 1.2 to 3.3; p = 0.01) for late HF associated with trastuzumab treatment.
Conclusions Trastuzumab treatment is associated with a 2-fold increased risk of late HF compared with chemotherapy treatment alone.
↵∗ Drs. Schou and Møller contributed equally to this work and are joint senior authors.
Supported by Danish Heart Foundation grants 14-R97-A5188-22839 and 15-R99-A5940; and the Research Fond of the Region of Southern Denmark, Vejle, to Dr. Banke during her PhD study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received June 24, 2018.
- Revision received September 5, 2018.
- Accepted September 19, 2018.
- 2019 American College of Cardiology Foundation
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