Breast Cancer Research and Treatment

, Volume 144, Issue 1, pp 163–170 | Cite as

Risk of cardiovascular adverse events from trastuzumab (Herceptin®) in elderly persons with breast cancer: a population-based study

  • H.-T. Tsai
  • C. Isaacs
  • A. Z. Fu
  • J. L. Warren
  • A. N. Freedman
  • A. Barac
  • C.-Y. Huang
  • A. L. Potosky


Randomized controlled trials have reported a 4–5 times increased risk of heart failure (HF) in breast cancer patients receiving trastuzumab (Herceptin ® ) compared to patients who do not receive trastuzumab. However, data regarding the cardiac effects of trastuzumab on elderly patients treated in general practice remain very limited. Using the US surveillance, epidemiology, and end results (SEER)-Medicare database, we conducted a retrospective cohort study on the cardiac effects of trastuzumab use in all incident breast cancer patients diagnosed from 1998 to 2007 who were 66 years and older, had no prior recent claims for cardiomyopathy (CM) or HF, and were followed through 2009. We defined our outcome as the first CM/HF event after diagnosis. We performed Cox-proportional hazard models with propensity score adjustment to estimate CM/HF risk associated with trastuzumab use. A total of 6,829 out of 68,536 breast cancer patients (median age: 75) had an incident CM/HF event. Patients who received trastuzumab tended to be younger, non-white, diagnosed more recently, and had a stage IV diagnosis. Trastuzumab use was associated with an increased risk of CM/HF (HR = 2.08, 95 % CI 1.77–2.44, p < 0.001). The trastuzumab-associated CM/HF risk was stronger in patients who were younger (HR = 2.52 for 66–75 years and HR = 1.44 for 76 years and older, p < 0.001) and diagnosed in recent years (HR = 2.58 for 2006–2007 vs. 1.86 for 1998–2005, p = 0.01). The twofold risk of CM/HF associated with trastuzumab remained regardless of patients’ diagnosis stage, presence of hypertension, cardiovascular comorbidities, or receipt of anthracyclines, taxanes, or radiation. Trastuzumab may double CM/HF risk among elderly breast cancer patients. Our findings reinforce the need to prevent and manage cardiac risk among elderly breast cancer patients receiving trastuzumab.


Trastuzumab Cardiomyopathy Heart failure Breast cancer Risk Adverse event 



This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. 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. This work was supported by the National Cancer Institute at the National Institutes of Health [Grant numbers HHSN2612000900651P, P30CA051008]; and the Georgetown and Howard Universities Center for Clinical and Translational Science (GHUCCTS) Post-doctoral KL2 Award [5KL2TR000102-04 to A.B.]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

Conflict of interest

Dr. Isaacs is on the speaker’s bureau of Genentech. Dr. Barac received research funding and honoraria for lectures from Genentech Inc. and consultancy fees from Cell Therapeutics Inc. All remaining authors have declared no conflicts of interest.

Supplementary material

10549_2014_2836_MOESM1_ESM.pdf (63 kb)
(PDF 63 kb)


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Copyright information

© Springer Science+Business Media New York (outside the USA) 2014

Authors and Affiliations

  • H.-T. Tsai
    • 1
  • C. Isaacs
    • 2
  • A. Z. Fu
    • 1
  • J. L. Warren
    • 3
  • A. N. Freedman
    • 3
  • A. Barac
    • 4
  • C.-Y. Huang
    • 5
  • A. L. Potosky
    • 1
  1. 1.Department of Oncology, Lombardi Comprehensive Cancer CenterGeorgetown UniversityWashingtonUSA
  2. 2.Department of Oncology, Lombardi Comprehensive Cancer CenterGeorgetown UniversityWashingtonUSA
  3. 3.Division of Cancer Control and Population SciencesNational Cancer InstituteBethesdaUSA
  4. 4.Division of CardiologyMedstar Washington Hospital CenterWashingtonUSA
  5. 5.Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins UniversityBaltimoreUSA

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