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Doxorubicin-induced cardiac dysfunction in unselected patients with a history of early-stage breast cancer

  • Epidemiology
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Abstract

Cardiomyopathy is a known complication of anthracycline-based adjuvant chemotherapy and is more commonly reported in population-based studies of breast cancer survivors than in clinical trials. This study prospectively evaluated the prevalence of elevated cardiac biomarkers in unselected patients who had been treated with doxorubicin for early-stage breast cancer and the prevalence of reduced LVEF in patients with an elevated biomarker. All participants underwent an examination, symptom inventory, medical record review, and biomarker analysis for BNP, troponin, and plasma and urine NT-proBNP. Patients who had one or more elevated biomarkers were referred for echocardiogram; systolic dysfunction was defined as LVEF less than 55 %. Multivariable logistic regression was used to determine the associations between age, BMI, cumulative dose of doxorubicin, diabetes, hypertension, and left-sided radiation therapy and the risk of reduced LVEF. Among the 269 patients who underwent lab testing (mean age 56 years, mean time since completion of doxorubicin-based chemotherapy 6 years), 192 (72 %) had one or more elevated biomarker. Among the 166 patients who completed an echocardiogram, 11.5 % had a LVEF < 55 %. After adjusting for covariates known to affect cardiac function, multivariable logistic regression revealed plasma NT-proBNP to be the only measured cardiac biomarker associated with systolic dysfunction. There is a relationship between NT-proBNP and the frequency of reduced LVEF in women treated with doxorubicin for curative intent; further study of NT-proBNP as a potential biomarker for subclinical cardiac dysfunction after exposure to anthracyclines is warranted.

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Abbreviations

LVEF:

Left ventricular ejection fraction

BNP:

Brain natriuretic peptide

NT:

N-terminal

BMI:

Body mass index

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Acknowledgments

The authors of the study would like to acknowledge the work and efforts of the University of Michigan Clinical Trials Office (CTO) Mobile Clinical Research Unit and the CTO Specimen Core and Processing Lab. In addition, the study would not have been possible without the willing participation of our patients and the efforts by the staff in the breast cancer clinic, especially the physician assistants and nurse practitioners who were dedicated to facilitating patient recruitment.

Conflict of interest

All authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Ethical standards

The experiments performed comply with the current laws of the United States.

Funding

This study was funded by a Pfizer Foundation Fellowship Grant awarded to Dr. Cooney as the PI in support of Dr. Caram’s effort and an intramural University of Michigan Cancer Research Committee Grant awarded to Jeffery Smerage, MD, PhD.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, United States

    Megan E. V. Caram, Jeffrey Smerage, N. Lynn Henry, Anne Schott, Daniel F. Hayes, Catherine Van Poznak, Kathleen A. Cooney & Jennifer J. Griggs

  2. Department of Biostatistics, University of Michigan School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, United States

    Cui Guo & Mousumi Banerjee

  3. Department of Internal Medicine, Division of Cardiology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive; Cardiovascular Center, Ann Arbor, MI, 48109, United States

    Monika Leja, Melvyn Rubenfire & Melinda Davis

  4. Department of Pathology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, United States

    Donald Giacherio

  5. Department of Urology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, United States

    Kathleen A. Cooney

  6. Department of Pharmacology, College of Pharmacy, University of Michigan , 428 Church Street, Ann Arbor, MI, 48104–1065, United States

    Daniel L. Hertz

  7. Department of Health Management and Policy, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, 48109, United States

    Jennifer J. Griggs

Authors
  1. Megan E. V. Caram
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  2. Cui Guo
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  3. Monika Leja
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  4. Jeffrey Smerage
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  5. N. Lynn Henry
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  6. Donald Giacherio
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  7. Melvyn Rubenfire
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  8. Anne Schott
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  9. Melinda Davis
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  10. Daniel F. Hayes
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  11. Catherine Van Poznak
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  12. Kathleen A. Cooney
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  13. Daniel L. Hertz
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  14. Mousumi Banerjee
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  15. Jennifer J. Griggs
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Corresponding author

Correspondence to Megan E. V. Caram.

Appendix

Appendix

See Table 3.

Table 3 BNP & NT-proBNP limits
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Caram, M.E.V., Guo, C., Leja, M. et al. Doxorubicin-induced cardiac dysfunction in unselected patients with a history of early-stage breast cancer. Breast Cancer Res Treat 152, 163–172 (2015). https://doi.org/10.1007/s10549-015-3454-8

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  • DOI: https://doi.org/10.1007/s10549-015-3454-8

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