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Evaluation of radiation-induced cardiac toxicity in breast cancer patients treated with Trastuzumab-based chemotherapy

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Abstract

Purpose

Patients with Her2-positive breast cancer treated with trastuzumab have higher rates of cardiotoxicity (CT). Left-breast radiation might increase the risk for CT from cardiac exposure to radiation. The goal of our study is to evaluate the contribution of radiotherapy (RT) in the development of CT in breast cancer patients receiving trastuzumab.

Methods

Two hundred and two patients were treated with RT and trastuzumab from 2000 to 2014. The RT plans for left-side disease were recalled from archives. The heart, each chamber, and left anterior descending artery (LAD) were independently contoured. New dose-volume histograms (DVH) were generated. Their serial left-ventricular ejection fractions (LVEF) were studied. CT for left and right side were compared using Fisher’s exact test. The DVH data were correlated with the predefined cardiac events using actuarial Cox regression analysis.

Results

Compared to the right sided, the left-side cases showed statistically significant development of arrhythmia (14.2%) versus (< 1%) (p < 0.001). Cardiac ischemia was found in 10 patients in left and one patient in right side (p = 0.011). The equivalent uniform dose (EUD) to the left ventricle (LV), right ventricle (RV), and LAD was significantly associated with decrease in LVEF by > 10% (p = 0.037, p = 0.023 and p = 0.049, respectively).

Conclusions

Among patients treated for left-sided lesions, there were no significant differences in EF decline. However, there was a higher rate of ischemia and arrhythmia compared to those with right-sided disease. The EUD index of LV, RV, and LAD could be considered as a parameter to describe the risk of radiation-induced CT.

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References

  1. Siegel RL, Miller KD, Jemal A (2017) Cancer, statistics. CA: Cancer J Clin 2017 67:7

    Google Scholar 

  2. Berry DA, Cronin KA, Plevritis SK et al (2005) Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med 353 17:1784–1792

    Article  Google Scholar 

  3. Darby S, McGale P, Correa C et al (2011) Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet 378:1707–1716

    Article  CAS  PubMed  Google Scholar 

  4. Clarke M, Collins R, Darby S et al (2005) Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366(9503):2087–2106

    Article  CAS  PubMed  Google Scholar 

  5. Rehammar JC, Jensen MB, McGale P et al (2017) Risk of heart disease in relation to radiotherapy and chemotherapy with anthracyclines among 19,464 breast cancer patients in Denmark, 1977–2005. Radiother Oncol 123:299–305

    Article  PubMed  PubMed Central  Google Scholar 

  6. Taunk NK, Haffty BG, Kostis JB, Goyal S (2015) Radiation-induced heart disease: pathologic abnormalities and putative mechanisms. Front Oncol 5:39

    Article  PubMed  PubMed Central  Google Scholar 

  7. Taylor CW, Nisbet A, McGale P et al (2007) Cardiac exposures in breast cancer radiotherapy: 1950s–1990s Int J Radiat Oncol Biol Phys 69:1484– 1495

  8. 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

  9. Ewer MS, Vooletich MT, Durand JB et al (2005) Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol 23:7820–7826

  10. https://www.rtog.org/LinkClick.aspx?fileticket=eVB451KQ83M%3d&tabid=429

  11. Niemierko A (1997) Reporting and analyzing dose distributions: a concept of Equivalent Uniform Dose (EUD). Med Phys 24(1):17–26

    Article  Google Scholar 

  12. Caussa L, Kirova YM, Gault N et al (2011) The acute skin and heart toxicity of a concurrent association of trastuzumab and locoregional breast radiotherapy including internal mammary chain: a single-institution study. Eur J Cancer Oxf Engl 47:65–73

    Article  CAS  Google Scholar 

  13. Guarneri V, Lenihan DJ, Valero V et al (2006) Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience. J Clin Oncol 24(25):4107–4115

    Article  CAS  PubMed  Google Scholar 

  14. Halyard MY, Pisansky TM, Dueck AC et al (2009) Radiotherapy and adjuvant trastuzumab in operable breast cancer: tolerability and adverse event data from the NCCTG Phase III Trial N9831. J Clin Oncol 27:2638–2644

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Shaffer R, Tyldesley S, Rolles M et al (2009) Acute cardiotoxicity with concurrent trastuzumab and radiotherapy including internal mammary chain nodes: a retrospective single-institution study. Radiother Oncol 90:122–126

    Article  CAS  PubMed  Google Scholar 

  16. Cao L, Cai G, Chang C et al (2016) Early cardiac toxicity following adjuvant radiotherapy of left-sided breast cancer with or without concurrent trastuzumab. Oncotarget 7:1042–1054

    PubMed  Google Scholar 

  17. Darby SC, Ewertz M, McGalle P et al (2013) Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 368:987–998

    Article  CAS  PubMed  Google Scholar 

  18. Cheng YJ, Nie XY, Ji CC et al (2017) Long-term cardiovascular risk after radiotherapy in women with breast cancer. J Am Heart Assoc 6:e005633

    PubMed  PubMed Central  Google Scholar 

  19. Wu SP, Tam M, Vega RM, et al (2017) Effect of breast irradiation on cardiac disease in women enrolled in BCIRG-001 at 10-year follow-up. Int J Radiat Oncol Biol Phys 99(3):541–548

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, 100 Blossom Street, Boston, MA, 02114, USA

    Mohamed Abouegylah, Andrzej Niemierko, Samantha K. Edgington, Kyla Remillard, Brian Napolitano, George E. Naoum, Hoda E. Sayegh, Tessa Gillespie & Alphonse G. Taghian

  2. Department of Clinical Oncology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

    Mohamed Abouegylah, Mohamed Farouk & Abdelsalam A. Ismail

  3. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA

    Lior Z. Braunstein

  4. Department of Clinical Oncology, Faculty of Medicine, Tanta University, Tanta, Egypt

    Mohamed A. Alm El-Din

  5. Charles E Schmidit COM, (FAU), Boca Raton, FL, USA

    Laura Salama

  6. Department of Clinical Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

    Mostafa Elebrashi

Authors
  1. Mohamed Abouegylah
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  2. Lior Z. Braunstein
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  3. Mohamed A. Alm El-Din
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  4. Andrzej Niemierko
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  5. Laura Salama
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  6. Mostafa Elebrashi
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  7. Samantha K. Edgington
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  8. Kyla Remillard
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  9. Brian Napolitano
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  10. George E. Naoum
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  11. Hoda E. Sayegh
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  12. Tessa Gillespie
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  13. Mohamed Farouk
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  14. Abdelsalam A. Ismail
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  15. Alphonse G. Taghian
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Corresponding author

Correspondence to Alphonse G. Taghian.

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Conflict of interest

All the authors declare that he/she has no conflict of interest.

Ethical approval

All procedures performed in 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. This study was approved by the IRB.

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Abouegylah, M., Braunstein, L.Z., Alm El-Din, M.A. et al. Evaluation of radiation-induced cardiac toxicity in breast cancer patients treated with Trastuzumab-based chemotherapy. Breast Cancer Res Treat 174, 179–185 (2019). https://doi.org/10.1007/s10549-018-5053-y

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  • DOI: https://doi.org/10.1007/s10549-018-5053-y

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