Clinical Research
Heart Failure
Incidence of Heart Failure or Cardiomyopathy After Adjuvant Trastuzumab Therapy for Breast Cancer

https://doi.org/10.1016/j.jacc.2012.07.068Get rights and content
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Objectives

The purpose of this study was to estimate heart failure (HF) and cardiomyopathy (CM) rates after adjuvant trastuzumab therapy and chemotherapy in a population of older women with early-stage breast cancer.

Background

Newer biologic therapies for breast cancer such as trastuzumab have been reported to increase HF and CM in clinical trials, especially in combination with anthracycline chemotherapy. Elderly patients, however, typically have a higher prevalence of cardiovascular risk factors and have been underrepresented in trastuzumab clinical trials.

Methods

Using Surveillance, Epidemiology, and End Results-Medicare data from 2000 through 2007, we identified women 67 to 94 years of age with early-stage breast cancer. We calculated 3-year incidence rates of HF or CM for the following mutually exclusive treatment groups: trastuzumab (with or without nonanthracycline chemotherapy), anthracycline plus trastuzumab, anthracycline (without trastuzumab and with or without nonanthracycline chemotherapy), other nonanthracycline chemotherapy, or no adjuvant chemotherapy or trastuzumab therapy. HF or CM events were ascertained from administrative Medicare claims. Poisson regression was used to quantify risk of HF or CM, adjusting for sociodemographic factors, cancer characteristics, and cardiovascular conditions.

Results

We identified 45,537 older women (mean age: 76.2 years, standard deviation: 6.2 years) with early-stage breast cancer. Adjusted 3-year HF or CM incidence rates were higher for patients receiving trastuzumab (32.1 per 100 patients) and anthracycline plus trastuzumab (41.9 per 100 patients) compared with no adjuvant therapy (18.1 per 100 patients, p < 0.001). Adding trastuzumab to anthracycline therapy added 12.1, 17.9, and 21.7 HF or CM events per 100 patients over 1, 2, and 3 years of follow-up, respectively.

Conclusions

HF or CM are common complications after trastuzumab therapy for older women, with higher rates than those reported from clinical trials.

Key Words

anthracycline
cardiomyopathy
chemotherapy
epidemiology
heart failure
trastuzumab

Abbreviations and Acronyms

A+T
anthracycline plus trastuzumab
CI
confidence interval
CM
cardiomyopathy
HF
heart failure
ICD-9-CM
International Classification of Disease-9th Revision-Clinical Modification
IRR
incidence rate ratio
LVEF
left ventricular ejection fraction
SEER
Surveillance, Epidemiology, and End Results

Cited by (0)

This work was funded by an American Heart Association Grant-in-Aid Award (12GRNT9580005) and by a collaborative agreement sponsored by the Cardiology Service of Memorial Sloan-Kettering Cancer Center. Dr. Chen is supported by an Agency for Healthcare Research and Quality Career Development Award (1K08HS018781-01). Dr. Hurria is a consultant to Celegene, GlaxoSmithKline, Abraxis Bioscience, GTX, AMGEN, and Genentech. Dr. Steingart is a member of the Cardiac Safety Review Committee for Celgene. Dr. Gross has received research-related funding from Medtronic and serves on the Scientific Advisory Board of Fair Health, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.