Skip to main content

Advertisement

SpringerLink
Log in

Assessment of left ventricular function by CMR versus MUGA scans in breast cancer patients receiving trastuzumab: a prospective observational study

  • Original Paper
  • Published:
The International Journal of Cardiovascular Imaging Aims and scope Submit manuscript

Abstract

Little is known about the comparison of multiple-gated acquisition (MUGA) scanning with cardiovascular magnetic resonance (CMR) for serial monitoring of HER2+ breast cancer patients receiving trastuzumab. The association of cardiac biomarkers with CMR left ventricular (LV) function and volume is also not well studied. Our objectives were to compare CMR and MUGA for left ventricular ejection fraction (LVEF) assessment, and to examine the association between changes in brain natriuretic peptide (NT-BNP) and troponin-I and changes in CMR LV function and volume. This prospective longitudinal two-centre cohort study recruited HER2+ breast cancer patients between January 2010 and December 2013. MUGA, CMR, NT-BNP and troponin-I were performed at baseline, 6, 12, and 18 months after trastuzumab initiation. In total, 41 patients (age 51.7 ± 10.8 years) were enrolled. LVEF comparison between MUGA and CMR demonstrated weak agreement (Lin’s correlation coefficient r = 0.46, baseline; r = 0.29, 6 months; r = 0.42, 12 months; r = 0.39, 18 months; all p < 0.05). Bland–Altman plots demonstrated wide LVEF agreement limits (pooled agreement limits 3.0 ± 6.2). Both modalities demonstrated significant LVEF decline at 6 and 12 months from baseline, concomitant with increased LV volumes on CMR. Changes in NT-BNP correlated with changes in LV diastolic volume at 12 and 18 months (p < 0.05), and LV systolic volume at 18 months (p < 0.05). Changes in troponin-I did not correlate with changes in LV function or volume at any timepoint. In conclusion, CMR and MUGA LVEF are not interchangeable, warranting selection and utility of one modality for serial monitoring. CMR is useful due to less radiation exposure and accuracy of LV volume measurements. Changes in NT-BNP correlated with changes in LV volumes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM et al (2011) Global Cancer Statistics: 2011. CA Cancer J Clin 61:69–90. https://doi.org/10.3322/caac.20107

    Article  Google Scholar 

  2. Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182

    Article  CAS  Google Scholar 

  3. Owens MA, Horten BC, Da Silva MM (2004) HER2 amplification ratios by fluorescence in situ hybridiaztion and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues. Clin Breast Cancer 5:63–69. https://doi.org/10.3816/CBC.2004.n.011

    Article  CAS  PubMed  Google Scholar 

  4. Carter P, Presta L, Gormant CM et al (1992) Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci USA 89:4285–4289

    Article  CAS  Google Scholar 

  5. Seshadri R, Firgaira FA, Horsfall DJ et al (1993) Clinical significance of HER-2/neu oncogene amplification in primary breast cancer. J Clin Oncol 11:1936–1942

    Article  CAS  Google Scholar 

  6. Vogel C, Cobleigh M, Tripathy D et al (2002) Efficacy and safety of trastuzumab as single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20:719–726

    Article  CAS  Google Scholar 

  7. Hurley J, Coliny P, Reis I et al (2006) Docetaxel, cisplatin, and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2-positive locally advanced breast cancer. J Clin Oncol 24:1831–1838

    Article  CAS  Google Scholar 

  8. Joensuu H, Kellokumpu-Lehtinen P-L, Bono P et al (2006) Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 354:809–820

    Article  CAS  Google Scholar 

  9. Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672

    Article  CAS  Google Scholar 

  10. Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684

    Article  CAS  Google Scholar 

  11. 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. https://doi.org/10.1200/JCO.2005.04.173

    Article  CAS  PubMed  Google Scholar 

  12. Seidman A, Hudis C, Pierri M et al (2002) Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 20:1215–1221

    Article  CAS  Google Scholar 

  13. Slamon D, Eiermann W, Robert N et al (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273–1283

    Article  CAS  Google Scholar 

  14. Perez EA, Rodeheffer R (2004) Clinical cardiac tolerability of trastuzumab. J Clin Oncol 22:322–329. https://doi.org/10.1200/JCO.2004.01.120

    Article  CAS  PubMed  Google Scholar 

  15. Goldhar HA, Yan AT, Ko DT et al (2016) The temporal risk of heart failure associated with adjuvant trastuzumab in breast cancer patients: a population study. J Natl Cancer Inst 108:djv301

    Article  Google Scholar 

  16. Bellenger NG, Burgess MI, Ray SG et al (2000) Comparison of left ventricular ejection fraction and volumes in heart failure by echocardiography, radionuclide ventriculography and cardiovascular magnetic resonance. Are they interchangeable? Eur Heart J 21:1387–1396. https://doi.org/10.1053/euhj.2000.2011

    Article  CAS  PubMed  Google Scholar 

  17. Einstein AJ, Henzlova MJ, Rajagopalan S (2008) Estimating risk of cancer associated with radiation exposure from 64-slice computed tomography coronary angiography. JAMA 298(3):317–323. https://doi.org/10.1001/jama.298.3.317

    Article  Google Scholar 

  18. Einstein AJ, Moser KW, Thompson RC et al (2007) Radiation dose to patients from cardiac diagnostic imaging. Circulation 116:1290–1305. https://doi.org/10.1161/CIRCULATIONAHA.107.688101

    Article  PubMed  Google Scholar 

  19. Grothues F, Smith GC, Moon JC et al (2002) Comparison of interstudy reproducibility of cardiovascular magnetic resonance with two-dimensional echocardiography in normal subjects and in patients with heart failure or left ventricular hypertrophy. J Am Coll Cardiol 90:29–34

    Article  Google Scholar 

  20. Chung AK, Das SR, Leonard D et al (2006) Women have higher left ventricular ejection fractions than men independent of differences in left ventricular volume. Circulation 113:1597–1604. https://doi.org/10.1161/CIRCULATIONAHA.105.574400

    Article  PubMed  Google Scholar 

  21. Vasan R, Benjamin E, Larson M et al (2002) Plasma natriuretic peptides for community screening for left ventricular hypertrophy and systolic dysfunction: the Framingham heart study. JAMA 288:1252–1259

    Article  CAS  Google Scholar 

  22. Redfield MM, Rodeheffer RJ, Jacobsen SJ et al (2004) Plasma brain natriuretic peptide to detect preclinical ventricular systolic or diastolic dysfunction. Circulation 109:3176–3181. https://doi.org/10.1161/01.CIR.0000130845.38133.8F

    Article  CAS  PubMed  Google Scholar 

  23. Babuin L, Jaffe AS (2005) Troponin: the biomarker of choice for the detection of cardiac injury. CMAJ 173:1191–1202

    Article  Google Scholar 

  24. Kilickap S, Barista I, Akgul E et al (2005) cTnT can be a useful marker for early detection of anthracycline cardiotoxicity. Ann Oncol 16:798–804. https://doi.org/10.1093/annonc/mdi152

    Article  CAS  PubMed  Google Scholar 

  25. Cardinale D, Sandri MT, Martinoni A et al (2000) Left ventricular dysfunction predicted by early Troponin I release after high-dose chemotherapy. J Am Coll Cardiol 36:517–522

    Article  CAS  Google Scholar 

  26. Cardinale D, Sandri MT, Colombo A et al (2004) Prognostic value of Troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation 109:2749–2755. https://doi.org/10.1161/01.CIR.0000130926.51766.CC

    Article  CAS  PubMed  Google Scholar 

  27. Barthur A, Brezden-Masley C, Connelly KA et al (2017) Longitudinal assessment of right ventricular structure and function by cardiovascular magnetic resonance in breast cancer patients treated with trastuzumab: a prospective observational study. J Cardiovasc Magn Reson 19:44. https://doi.org/10.1186/s12968-017-0356-4

    Article  PubMed  PubMed Central  Google Scholar 

  28. Mackey JR, Clemons M, Côté MA et al (2008) Cardiac management during adjuvant trastuzumab therapy: recommendations of the Canadian Trastuzumab Working Group. Curr Oncol 15:24–35. https://doi.org/10.3747/co.2008.199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Carstensen B, Simpson J, Gurrin L (2008) Statistical models for assessing agreement in method comparison studies with replicate measurements. Int J Biostat 4:16

    Article  Google Scholar 

  30. Rothman KJ (1990) No adjustments are needed for multiple comparisons. Epidemiology 1:43–46. https://doi.org/10.1097/00001648-199001000-00010

    Article  CAS  Google Scholar 

  31. Walker J, Bhullar N, Fallah-rad N et al (2010) Role of three-dimensional echocardiography in breast cancer: comparison with two-dimensional echocardiography, multiple-gated acquisition scans, and cardiac magnetic resonance imaging. J Clin Oncol 28:3429–3436. https://doi.org/10.1200/JCO.2009.26.7294

    Article  PubMed  Google Scholar 

  32. Fallah-Rad N, Lytwyn M, Fang T et al (2008) Delayed contrast enhancement cardiac magnetic resonance imaging in trastuzumab induced cardiomyopathy. J Cardiovasc Magn Reson. 10:5. https://doi.org/10.1186/1532-429X-10-5

    Article  PubMed  PubMed Central  Google Scholar 

  33. Grover S, DePasquale C, Leong DP et al (2012) Early cardiac changes following anthracycline chemotherapy in breast cancer: a prospective multi-centre study using advanced cardiac imaging and biochemical markers. J Cardiovasc Magn Reson 14(Suppl 1):181. https://doi.org/10.1186/1532-429X-14-S1-P181

    Article  Google Scholar 

  34. Fallah-Rad N, Walker JR, Wassef A et al (2011) The utility of cardiac biomarkers, tissue velocity and strain imaging, and cardiac magnetic resonance imaging in predicting early left ventricular dysfunction in patients with human epidermal growth factor receptor II-positive breast cancer treated with a. J Am Coll Cardiol 57:2263–2270. https://doi.org/10.1016/j.jacc.2010.11.063

    Article  CAS  PubMed  Google Scholar 

  35. Sawaya H, Sebag IA, Plana JC et al (2011) Early detection and prediction of cardiotoxicity in chemotherapy-treated patients. Am J Cardiol 107:1375–1380. https://doi.org/10.1016/j.amjcard.2011.01.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Drafts BC, Twomley KM, D'Agostino R et al (2014) Low to moderate dose anthracycline-based chemotherapy is associated with early noninvasive imaging evidence of subclinical cardiovascular disease. JACC Cardiovasc Imaging 6(8):877–885. https://doi.org/10.1016/j.jcmg.2012.11.017.Low

    Article  Google Scholar 

  37. Chaosuwannakit N, D'Agostino RJ, Hamilton CA et al (2010) Aortic stiffness increases upon receipt of anthracycline chemotherapy. J Clin Oncol 28:166–172. https://doi.org/10.1200/JCO.2009.23.8527

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank all the study participants who contributed their time to this research study. We also acknowledge the study coordinators for their efforts in data collection. This work was supported by a Canadian Institute of Health Research Industry partnered grant with Hoffman-La Roche Canada Inc.

Funding

This work was supported by a Canadian Institute of Health Research Industry partnered grant with Hoffman-La Roche Canada Inc.

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, St. Michael’s Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada

    Vinita Dhir, Rashida Haq & Christine Brezden-Masley

  2. Terrence Donnelly Heart Centre, St. Michael’s Hospital, Toronto, ON, Canada

    Andrew T. Yan & Kim A. Connelly

  3. University of Toronto, Toronto, ON, Canada

    Andrew T. Yan, Kim A. Connelly, Rashida Haq, Anish Kirpalani, Kelvin K. W. Chan, Teresa M. Petrella & Christine Brezden-Masley

  4. Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON, Canada

    Andrew T. Yan, Kim A. Connelly, Anish Kirpalani & Christine Brezden-Masley

  5. Centre for Urban Health Solutions of the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON, Canada

    Rosane Nisenbaum

  6. Department of Medical Imaging, St. Michael’s Hospital, Toronto, ON, Canada

    Joanna Sloninko, Joseph Barfett & Anish Kirpalani

  7. Sunnybrook Odette Cancer Centre, Toronto, ON, Canada

    Kelvin K. W. Chan & Teresa M. Petrella

  8. The Canadian Centre for Applied Research in Cancer Control, Toronto, ON, Canada

    Kelvin K. W. Chan

Authors
  1. Vinita Dhir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrew T. Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rosane Nisenbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joanna Sloninko
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kim A. Connelly
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joseph Barfett
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rashida Haq
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anish Kirpalani
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kelvin K. W. Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Teresa M. Petrella
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Christine Brezden-Masley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christine Brezden-Masley.

Ethics declarations

Conflict of Interest

C. Brezden-Masley has received research grant support and/or honoraria for educational activities and/or served as consultant to Roche.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committees (St. Michael’s Hospital and Sunnybrook Odette Cancer Centre) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dhir, V., Yan, A.T., Nisenbaum, R. et al. Assessment of left ventricular function by CMR versus MUGA scans in breast cancer patients receiving trastuzumab: a prospective observational study. Int J Cardiovasc Imaging 35, 2085–2093 (2019). https://doi.org/10.1007/s10554-019-01648-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10554-019-01648-z

Keywords

Search

Navigation