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

  • Epidemiology
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Abstract

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.

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References

  1. Curigliano G, Mayer EL, Burstein HJ et al (2010) Cardiac toxicity from systemic cancer therapy: a comprehensive review. Prog Cardiovasc Dis 53:94–104

    Article  CAS  PubMed  Google Scholar 

  2. Marty M, Cognetti F, Maraninchi D et al (2005) Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol 23:4265–4274

    Article  CAS  PubMed  Google Scholar 

  3. Gianni L, Dafni U, Gelber RD et al (2011) Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol 12:236–244

    Article  CAS  PubMed  Google Scholar 

  4. Romond EH, Jeong JH, Rastogi P et al (2012) Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 30:3792–3799

    Article  CAS  PubMed  Google Scholar 

  5. Bowles EJ, Wellman R, Feigelson HS et al (2012) Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J Natl Cancer Inst 104:1293–1305

    Article  CAS  PubMed  Google Scholar 

  6. Warren JL, Klabunde CN, Schrag D et al (2002) Overview of the SEER-Medicare data: content, research applications, and generalizability to the United States elderly population. Med Care 40:3–18

    Google Scholar 

  7. Klabunde CN, Potosky AL, Legler JM et al (2000) Development of a comorbidity index using physician claims data. J Clin Epidemiol 53:1258–1267

    Article  CAS  PubMed  Google Scholar 

  8. Kurth T, Walker AM, Glynn RJ et al (2006) Results of multivariable logistic regression, propensity matching, propensity adjustment, and propensity-based weighting under conditions of nonuniform effect. Am J Epidemiol 163:262–270

    Article  PubMed  Google Scholar 

  9. Rubin DB (1997) Estimating causal effects from large data sets using propensity scores. Ann Intern Med 127:757–763

    Article  CAS  PubMed  Google Scholar 

  10. Chen T, Xu T, Li Y et al (2011) Risk of cardiac dysfunction with trastuzumab in breast cancer patients: a meta-analysis. Cancer Treat Rev 37:312–320

    Article  CAS  PubMed  Google Scholar 

  11. Goldhirsch A, Gelber RD, Piccart-Gebhart MJ et al (2013) 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet 382:1021–1028

    Article  CAS  PubMed  Google Scholar 

  12. Serrano C, Cortes J, De Mattos-Arruda L et al (2012) Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors. Ann Oncol 23:897–902

    Article  CAS  PubMed  Google Scholar 

  13. Sengupta PP, Northfelt DW, Gentile F et al (2008) Trastuzumab-induced cardiotoxicity: heart failure at the crossroads. Mayo Clin Proc 83:197–203

    CAS  PubMed  Google Scholar 

  14. Geisberg C, Pentassuglia L, Sawyer DB (2012) Cardiac side effects of anticancer treatments: new mechanistic insights. Curr Heart Fail Rep 9:211–218

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Cote GM, Sawyer DB, Chabner BA (2012) ERBB2 inhibition and heart failure. N Engl J Med 367:2150–2153

    Article  CAS  PubMed  Google Scholar 

  16. Tarantini L, Cioffi G, Gori S et al (2012) Trastuzumab adjuvant chemotherapy and cardiotoxicity in real-world women with breast cancer. J Card Fail 18:113–119

    Article  CAS  PubMed  Google Scholar 

  17. Force T, Krause DS, Van Etten RA (2007) Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat Rev Cancer 7:332–344

    Article  CAS  PubMed  Google Scholar 

  18. Sliwkowski MX, Lofgren JA, Lewis GD et al (1999) Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin Oncol 26:60–70

    CAS  PubMed  Google Scholar 

  19. Keefe DL (2002) Trastuzumab-associated cardiotoxicity. Cancer 95:1592–1600

    Article  CAS  PubMed  Google Scholar 

  20. Birman-Deych E, Waterman AD, Yan Y et al (2005) Accuracy of ICD-9-CM codes for identifying cardiovascular and stroke risk factors. MedCare 43:480–485

    Google Scholar 

Download references

Acknowledgments

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.

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Authors and Affiliations

  1. Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3300 Whitehaven Street, NW, Suite 4100, Washington, DC, 20007, USA

    H.-T. Tsai, A. Z. Fu & A. L. Potosky

  2. Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Road, NW, Washington, DC, 20057, USA

    C. Isaacs

  3. Division of Cancer Control and Population Sciences, National Cancer Institute, 9609 Medical Center Drive, MSC 9762, Bethesda, MD, 20892, USA

    J. L. Warren & A. N. Freedman

  4. Division of Cardiology, Medstar Washington Hospital Center, 110 Irving Street, NW, Washington, DC, 20010, USA

    A. Barac

  5. Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 401N Broadway, Baltimore, MD, 21287, USA

    C.-Y. Huang

Authors
  1. H.-T. Tsai
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  2. C. Isaacs
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  3. A. Z. Fu
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  4. J. L. Warren
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  5. A. N. Freedman
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  6. A. Barac
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  7. C.-Y. Huang
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  8. A. L. Potosky
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Correspondence to H.-T. Tsai.

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Tsai, HT., Isaacs, C., Fu, A.Z. et al. Risk of cardiovascular adverse events from trastuzumab (Herceptin®) in elderly persons with breast cancer: a population-based study. Breast Cancer Res Treat 144, 163–170 (2014). https://doi.org/10.1007/s10549-014-2836-7

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  • DOI: https://doi.org/10.1007/s10549-014-2836-7

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