Author + information
- Anthony F. Yu, MDa,b,∗ (, )@AnthonyYuMD,
- Chaya S. Moskowitz, PhDc,
- Katherine Lee Chuy, MDd,
- Ji Yang, MDe,
- Chau T. Dang, MDa,b,
- Jennifer E. Liu, MDa,b,
- Kevin C. Oeffinger, MDf and
- Richard M. Steingart, MDa,b
- aDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- bWeill Cornell Medical College, New York, New York
- cDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
- dJohn H Stroger Jr Hospital of Cook County, Chicago, Illinois
- eNew York Presbyterian Brooklyn Methodist Hospital, New York, New York
- fDepartment of Medicine, Duke University Medical Center, Durham, North Carolina
- ↵∗Address for correspondence:
Dr. Anthony F. Yu, Department of Medicine, Cardiology Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10021.
Background Guidelines recommend left ventricular ejection fraction (LVEF) assessments every 3 months for cardiotoxicity monitoring during human epidermal growth factor receptor 2 (HER2) targeted therapy. Evidence in support of this practice is lacking.
Objectives This study examines the association between adherence to cardiotoxicity surveillance guidelines and heart failure (HF) in HER2-positive breast cancer patients.
Methods A case-control study was performed in 53 patients who developed cardiotoxicity during HER2 targeted therapy, and 159 controls matched by age, anthracycline exposure, and year of treatment. Cardiotoxicity was defined as HF (New York Heart Association functional class III or IV) or cardiac death. Adherence to cardiotoxicity surveillance guidelines was ascertained from the beginning of HER2 targeted therapy to the diagnosis date of HF for cases or the corresponding timepoint for matched controls. Conditional logistic regression was used for case-control comparisons.
Results Eighty-one percent of cases and controls were previously treated with an anthracycline. Adherence to cardiotoxicity surveillance guidelines during the entire observation period or during the first 6 months of treatment was not associated with lower risk of HF. An LVEF <55% at any surveillance timepoint was identified in 49% of cases and 3% of controls, and an LVEF <55% during the final surveillance timepoint before developing HF was identified in 54% of cases and 4% of controls. In multivariable-adjusted analyses, LVEF <55% at any timepoint or during the final surveillance timepoint (odds ratio: 27.0; 95% confidence interval: 9.3 to 78.8 and odds ratio: 25.6; 95% confidence interval: 7.3 to 90.3, respectively) was associated with HF.
Conclusions Patients with LVEF <55% on routine surveillance during HER2 targeted therapy are at increased risk for HF. Additional studies to define their optimal management are warranted.
This work was funded by a grant from the National Cancer Institute (K23 CA218897) awarded to Dr. Yu. This work was funded in part by the National Institutes of Health (P30 CA008748 and UL1 TR002384). Dr. Yu has received personal fees from Eidos Therapeutics, Genentech, and Glenmark Pharmaceuticals. Dr. Dang has been on advisory boards for Roche/Genentech, Puma, Lilly USA, and Daiichi; and has received grants to Memorial Sloan Kettering Cancer Center from Roche/Genentech and Puma. Dr. Liu has received personal fees from Pfizer and Bay Labs. Dr. Steingart has received personal fees from Pfizer and Celgene. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: CardioOncology author instructions page.
- Received January 22, 2020.
- Revision received March 5, 2020.
- Accepted March 14, 2020.
- 2020 The Authors