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Cardiac safety of non-anthracycline trastuzumab-based therapy for HER2-positive breast cancer

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Trastuzumab improves overall survival for women with HER2-positive breast cancer but is associated with cardiotoxicity, especially when administered after anthracyclines. Use of non-anthracycline trastuzumab-based regimens is rising, particularly for patients with low-risk disease or with multiple cardiovascular risk factors. We performed a single-center retrospective cohort study to assess the cardiac safety of trastuzumab without anthracyclines outside of a clinical trial setting.

Methods

A retrospective chart review was conducted of patients with HER2-positive early-stage breast cancer receiving non-anthracycline trastuzumab-based therapy between January 2010 and June 2014. Cardiovascular risk factors, left ventricular ejection fraction (LVEF), and treatment interruption data were collected. The primary outcome was a cardiac event (CE), defined by New York Heart Association class III or IV heart failure or cardiac death. The secondary outcome was a significant asymptomatic decline of LVEF (>10% to <55% or >16% from baseline).

Results

A total of 165 patients were identified with a median age of 59 years (range 32–85 years). Seventy (42%) had hypertension, 52 (32%) had hyperlipidemia, 29 (18%) had diabetes, and 5 (3%) had coronary artery disease. All patients had a LVEF >50% (median 67%; range 50–80%) at baseline. Two (1.2%) patients with multiple cardiovascular risk factors developed a CE. After discontinuation of trastuzumab, both patients had recovery of LVEF to >50% and resolution of heart failure symptoms. Ten (6.1%) patients developed significant asymptomatic LVEF decline during trastuzumab therapy.

Conclusions

The overall incidence of symptomatic heart failure and asymptomatic LVEF decline among patients receiving trastuzumab without anthracyclines remains low. These findings suggest that less intensive cardiac monitoring may be appropriate during trastuzumab therapy without anthracyclines.

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References

  1. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353(16):1673–1684

    Article  CAS  PubMed  Google Scholar 

  2. Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M et al (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365(14):1273–1283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ezaz G, Long JB, Gross CP, Chen J (2014) Risk prediction model for heart failure and cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Heart Assoc 3(1):e000472

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bowles EJ, Wellman R, Feigelson HS, Onitilo AA, Freedman AN, Delate T, Allen LA, Nekhlyudov L, Goddard KA, Davis RL 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(17):1293–1305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chen J, Long JB, Hurria A, Owusu C, Steingart RM, Gross CP (2012) Incidence of heart failure or cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Coll Cardiol 60(24):2504–2512

    Article  CAS  PubMed  Google Scholar 

  6. Thavendiranathan P, Abdel-Qadir H, Fischer HD, Camacho X, Amir E, Austin PC, Lee DS (2016) Breast cancer therapy-related cardiac dysfunction in adult women treated in routine clinical practice: a population-based cohort study. J Clin Oncol 34(19):2239–2246

    Article  PubMed  Google Scholar 

  7. Burstein HJ, Piccart-Gebhart MJ, Perez EA, Hortobagyi GN, Wolmark N, Albain KS, Norton L, Winer EP, Hudis CA (2012) Choosing the best trastuzumab-based adjuvant chemotherapy regimen: should we abandon anthracyclines? J Clin Oncol 30(18):2179–2182

    Article  CAS  PubMed  Google Scholar 

  8. Giordano SH, Lin YL, Kuo YF, Hortobagyi GN, Goodwin JS (2012) Decline in the use of anthracyclines for breast cancer. J Clin Oncol 30(18):2232–2239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Morris PG, Hudis CA (2010) Trastuzumab-related cardiotoxicity following anthracycline-based adjuvant chemotherapy: how worried should we be? J Clin Oncol 28(21):3407–3410

    Article  CAS  PubMed  Google Scholar 

  10. Robson D, Verma S (2009) Anthracyclines in early-stage breast cancer: is it the end of an era? Oncologist 14(10):950–958

    Article  CAS  PubMed  Google Scholar 

  11. Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis M, Shapira I et al (2015) Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med 372(2):134–141

    Article  PubMed  PubMed Central  Google Scholar 

  12. Dang C, Guo H, Najita J, Yardley D, Marcom K, Albain K, Rugo H, Miller K, Ellis M, Shapira I et al (2016) Cardiac outcomes of patients receiving adjuvant weekly paclitaxel and trastuzumab for node-negative, ERBB2-positive breast cancer. JAMA Oncol 2(1):29–36

    Article  PubMed  Google Scholar 

  13. Jones SE, Collea R, Paul D, Sedlacek S, Favret AM, Gore I Jr, Lindquist DL, Holmes FA, Allison MA, Brooks BD et al (2013) Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a single-group, open-label, phase 2 study. Lancet Oncol 14(11):1121–1128

    Article  CAS  PubMed  Google Scholar 

  14. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS et al (2005) Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 18(12):1440–1463

    Article  PubMed  Google Scholar 

  15. Yu AF, Yadav NU, Eaton AA, Lung BY, Thaler HT, Liu JE, Hudis CA, Dang CT, Steingart RM (2015) Continuous trastuzumab therapy in breast cancer patients with asymptomatic left ventricular dysfunction. Oncologist 20(10):1105–1110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M, Ganame J, Sebag IA, Agler DA, Badano LP et al (2014) Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 27(9):911–939

    Article  PubMed  Google Scholar 

  17. Slamon DJ, Eierman W, Robert NJ, Giermek J, Martin M, Jasiowka M, Mackey JR, Chan A, Liu MC, Pinter T, Valero V, Falkson C, Fornander T, Shiftan TA, Bensfia S, Hitier S, Xu N, Bee-Munteanu V, Drevot P, Press MF, Crown J. Ten year follow-up of the BCIRG-006 trial comparing doxorubicin plus cyclophosphamide followed by docetaxel (AC-T) with doxorubicin plus cyclophosphamide followed by docetaxel and trastuzumab (AC-TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2+ early breast cancer patients [abstract]. In: Proceedings of the 38th Annual Meeting of the CTRC-AACR San Antonio Breast Cancer Symposium; 2015 Dec 8–12; San Antonio, TX. Philadelphia (PA); 2016. Abstract S5-04

  18. de Azambuja E, Procter MJ, van Veldhuisen DJ, Agbor-Tarh D, Metzger-Filho O, Steinseifer J, Untch M, Smith IE, Gianni L, Baselga J et al (2014) Trastuzumab-Associated cardiac events at 8 years of median follow-up in the Herceptin adjuvant trial (BIG 1-01). J Clin Oncol 32(20):2159–2165

    Article  PubMed  Google Scholar 

  19. Romond EH, Jeong JH, Rastogi P, Swain SM, Geyer CE Jr, Ewer MS, Rathi V, Fehrenbacher L, Brufsky A, Azar CA 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(31):3792–3799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Advani PP, Ballman KV, Dockter TJ, Colon-Otero G, Perez EA (2016) Long-term cardiac safety analysis of NCCTG N9831 (alliance) adjuvant trastuzumab trial. J Clin Oncol 34(6):581–587

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748.

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Authors and Affiliations

  1. Department of Medicine, Cardiology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Anthony F. Yu, Roy B. Mukku, Jennifer E. Liu & Richard M. Steingart

  2. Department of Cardiology, Maimonides Medical Center, Brooklyn, NY, USA

    Shivani Verma

  3. Department of Medicine, Division of Survivorship and Supportive Care, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Kevin C. Oeffinger

  4. Department of Medicine, Breast Medicine Service, Memorial Sloan Kettering Cancer Center, Brooklyn, NY, USA

    Clifford A. Hudis & Chau T. Dang

Authors
  1. Anthony F. Yu
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  2. Roy B. Mukku
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  3. Shivani Verma
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  4. Jennifer E. Liu
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  5. Kevin C. Oeffinger
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  6. Richard M. Steingart
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  7. Clifford A. Hudis
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  8. Chau T. Dang
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Contributions

Drs. Yu and Dang had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to Anthony F. Yu.

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Conflict of interest

Dr. Dang receives research funding from Roche/Genentech and GlaxoSmithKline.

Disclosure

No other disclosures are reported. All remaining authors have declared no conflict of interest.

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Yu, A.F., Mukku, R.B., Verma, S. et al. Cardiac safety of non-anthracycline trastuzumab-based therapy for HER2-positive breast cancer. Breast Cancer Res Treat 166, 241–247 (2017). https://doi.org/10.1007/s10549-017-4362-x

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  • DOI: https://doi.org/10.1007/s10549-017-4362-x

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