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Trastuzumab mediated cardiotoxicity in the setting of adjuvant chemotherapy for breast cancer: a retrospective study
Authors:Deepa Wadhwa  Nazanin Fallah-Rad  Debjani Grenier  Marianne Krahn  Tielan Fang  Roien Ahmadie  Jonathan R. Walker  Danica Lister  Rakesh C. Arora  Ivan Barac  Andrew Morris  Davinder S. Jassal
Affiliation:1. Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
2. Cardiology Division, Department of Cardiac Sciences, Institute of Cardiovascular Sciences, St. Boniface General Hospital, University of Manitoba, Winnipeg, Manitoba, Canada
3. Oncology Division, Department of Internal Medicine, St. Boniface General Hospital, University of Manitoba, Winnipeg, Manitoba, Canada
4. Department of Pharmacy, CancerCare Manitoba, Winnipeg, Manitoba, Canada
5. Cardiac Surgery Division, Department of Cardiac Sciences, St. Boniface General Hospital, University of Manitoba, Winnipeg, Manitoba, Canada
6. Cardiology Division, Department of Cardiac Sciences, St. Boniface General Hospital, University of Manitoba, Rm Y3010, Bergen Cardiac Care Centre, 409 Taché Avenue, Winnipeg, Manitoba, Canada, R2H 2A6
7. Department of Radiology, St. Boniface General Hospital, University of Manitoba, Winnipeg, Manitoba, Canada
Abstract:Background The incidence and management of trastuzumab-mediated cardiotoxicity outside of clinical trials has not been well described. Objective and methods The aim of the study was to retrospectively evaluate the incidence of cardiac dysfunction, characterize its natural history, and identify the degree of reversibility using cardiac MRI, in a population of HER-2 positive breast cancer patients receiving trastuzumab in the adjuvant setting. Results Out of 152 patients (mean age 52 ± 10 years), 36 (24%) developed trastuzumab mediated cardiomyopathy, the majority asymptomatic. Factors that predicted the development of trastuzumab mediated cardiac dysfunction were a pre-existing history of hypertension, smoking history, and a family history of coronary artery disease. Within 3 months of treatment with trastuzumab, there was a difference in LVEF between the normal cohort and those patients who developed LV systolic dysfunction (61 ± 5% vs. 51 ± 8%, P < 0.01). During the 6-month-followup, 34/36 patients demonstrated subepicardial linear delayed enhancement of the lateral wall of the left ventricle on cardiac MRI, suggesting trastuzumab induced myocarditis. Conclusion Approximately 1 in 4 women may develop LV systolic dysfunction after treatment with adjuvant trastuzumab, necessitating careful patient selection and close serial monitoring using noninvasive cardiac imaging.
Keywords:Trastuzumab  Breast cancer  Cardiomyopathy
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