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Cardiovascular events, early discontinuation of trastuzumab, and their impact on survival

  • Epidemiology
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Abstract

To evaluate how often trastuzumab therapy is ended early (i.e., early discontinuation) and how cardiovascular events and early discontinuation affect survival among older women with breast cancer. A population-based cohort of female Medicare beneficiaries with stage I–III breast cancer in 2005–2009 who received trastuzumab was assembled and followed through 2011. Completed trastuzumab treatment was defined as ≥11 months of continuous trastuzumab treatments with no delay between trastuzumab treatments >45 days. We identified trastuzumab-associated cardiovascular events as those occurring within 45 days before or after the last trastuzumab treatment. Using Cox proportional hazard models, we examined the association between early discontinuation of trastuzumab and cardiovascular events on all-cause mortality. Our cohort consisted of 585 women (mean age: 71.6 years). Approximately 41 % of women discontinued trastuzumab therapy early. Patients with early discontinuation of trastuzumab were more likely to have heart failure /cardiomyopathy, atrial fibrillation, and other cardiovascular events than women who completed trastuzumab. Cardiovascular events were strongly associated with an increased risk of all-cause mortality [adjusted hazard ratio (AHR) 3.54; 95 % confidence interval (CI) 1.87 to 6.68]. Women with early discontinuation of trastuzumab had a non-significant increase in risk of all-cause mortality (AHR: 1.74; 95 % CI 0.94 to 3.23), compared to women who completed trastuzumab. Early trastuzumab discontinuation was common among older patients, and often associated with adverse cardiovascular events. Development of cardiovascular events was associated with a higher mortality risk than early trastuzumab discontinuation, implying that reducing cardiovascular complications from trastuzumab therapy could likely have a substantive impact on overall survival in this population.

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Acknowledgments

The collection of the California cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention’s National Program of Cancer Registries, under agreement #U55/CCR921930-02 awarded to the Public Health Institute. The authors of this report are responsible for its content. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California, Department of Public Health the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is not intended nor should be inferred. The authors acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare database. The interpretation and reporting of the SEER-Medicare data are the sole responsibility of the authors. This work was funded by an American Heart Association Grant-in-Aid Award (12GRNT9580005 to J Chen).

Conflict of interest

Dr. Gross receives support from Medtronic, Inc., Johnson & Johnson, and 21st Century Oncology. Dr. Gross is also a member of a scientific advisory board for FAIR Health, Inc. These supports were not used for any portion of the current manuscript. Dr. Hurria has received research support from Celgene Corporation and GlaxoSmithKline, and consulting fees from Seattle Genetics and GTx, Inc., for work performed outside the scope of this study. None of the other coauthors have conflicts to report.

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Authors and Affiliations

  1. Department of Chronic Disease Epidemiology, Yale School of Public Health, 60 College Street, P.O. Box 208034, New Haven, CT, 06520, USA

    Shi-Yi Wang

  2. Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale Cancer Center and Yale University School of Medicine, New Haven, CT, USA

    Shi-Yi Wang, Jessica B. Long & Cary P. Gross

  3. Department of Internal Medicine, Section of General Internal Medicine, Yale University School of Medicine, New Haven, USA

    Jessica B. Long & Cary P. Gross

  4. Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA

    Arti Hurria

  5. Division of Hematology/Oncology, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Cynthia Owusu

  6. Cardiology Service, Memorial Sloan-Kettering Cancer Center, New York, USA

    Richard M. Steingart

  7. Kaiser Permanente, Mid-Atlantic Permanente Research Institute, Rockville, MD, USA

    Jersey Chen

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  1. Shi-Yi Wang
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Correspondence to Shi-Yi Wang.

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Wang, SY., Long, J.B., Hurria, A. et al. Cardiovascular events, early discontinuation of trastuzumab, and their impact on survival. Breast Cancer Res Treat 146, 411–419 (2014). https://doi.org/10.1007/s10549-014-3029-0

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