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Coronary artery calcium in breast cancer survivors after radiation therapy

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Abstract

The purpose of the current study is to investigate whether breast cancer survivors after radiation therapy have a higher burden of coronary artery calcium as a potential surrogate of radiation-induced accelerated coronary artery disease. 333 patients were included. 54 patients underwent chest CT ≥ 6 months after the start of radiation therapy (radiation therapy group), while 279 patients had a CT scan either prior to or without undergoing radiation therapy (RT). Coronary artery calcium was quantified from CT by applying a threshold-based automated algorithm. Mean age at diagnosis was similar (p = 0.771) between RT (57.4 ± 13.1 years) and NoRT (58.0 ± 11.9 years). Median time between radiation therapy and CT was 2 years. The groups showed no significant differences in race, smoking history, cancer laterality, or cancer stage. 39 (72.2%) of RT patients had a coronary artery calcium score of 0, compared to 201 (72.0%) in patients without radiation therapy. Median coronary artery calcium burden for both groups was not significantly different (p = 0.982), nor when comparing patients who underwent left- versus right-sided radiation therapy (p = 0.453). When adjusting for the time between diagnosis and CT, radiation therapy patients had a significantly lower risk of a positive coronary artery calcium score. In conclusion, breast cancer survivors after radiation therapy are not more likely to show coronary artery calcium on follow-up CT imaging. Our results thus do not support radiation-induced accelerated coronary artery disease as an explanation for higher rates of heart disease in this group.

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References

  1. Berry DA, Cronin KA, Plevritis SK, Fryback DG, Clarke L, Zelen M, Mandelblatt JS, Yakovlev AY, Habbema JD, Feuer EJ, Cancer Intervention and Surveillance Modeling Network Collaborators (2005) Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med 353(17):1784–1792. doi:10.1056/NEJMoa050518

    Article  CAS  PubMed  Google Scholar 

  2. Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans E, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y, Early Breast Cancer Trialists’ Collaborative G (2005) 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. doi:10.1016/S0140-6736(05)67887-7

    Article  CAS  PubMed  Google Scholar 

  3. Giordano SH, Kuo YF, Freeman JL, Buchholz TA, Hortobagyi GN, Goodwin JS (2005) Risk of cardiac death after adjuvant radiotherapy for breast cancer. J Natl Cancer Inst 97(6):419–424. doi:10.1093/jnci/dji067

    Article  PubMed  PubMed Central  Google Scholar 

  4. Hooning MJ, Botma A, Aleman BM, Baaijens MH, Bartelink H, Klijn JG, Taylor CW, van Leeuwen FE (2007) Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst 99(5):365–375. doi:10.1093/jnci/djk064

    Article  PubMed  Google Scholar 

  5. Tuohinen SS, Skytta T, Poutanen T, Huhtala H, Virtanen V, Kellokumpu-Lehtinen PL, Raatikainen P (2016) Radiotherapy-induced global and regional differences in early-stage left-sided versus right-sided breast cancer patients: speckle tracking echocardiography study. Int J Cardiovasc Imaging. doi:10.1007/s10554-016-1021-y

    Google Scholar 

  6. Tuohinen SS, Skytta T, Virtanen V, Virtanen M, Luukkaala T, Kellokumpu-Lehtinen PL, Raatikainen P (2016) Detection of radiotherapy-induced myocardial changes by ultrasound tissue characterisation in patients with breast cancer. Int J Cardiovasc Imaging 32(5):767–776. doi:10.1007/s10554-016-0837-9

    Article  PubMed  Google Scholar 

  7. Aznar MC, Korreman SS, Pedersen AN, Persson GF, Josipovic M, Specht L (2011) Evaluation of dose to cardiac structures during breast irradiation. Br J Radiol 84(1004):743–746. doi:10.1259/bjr/12497075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mulliez T, Veldeman L, Speleers B, Mahjoubi K, Remouchamps V, Van Greveling A, Gilsoul M, Berwouts D, Lievens Y, Van den Broecke R, De Neve W (2015) Heart dose reduction by prone deep inspiration breath hold in left-sided breast irradiation. Radiother Oncol 114(1):79–84. doi:10.1016/j.radonc.2014.11.038

    Article  PubMed  Google Scholar 

  9. Shah C, Badiyan S, Berry S, Khan AJ, Goyal S, Schulte K, Nanavati A, Lynch M, Vicini FA (2014) Cardiac dose sparing and avoidance techniques in breast cancer radiotherapy. Radiother Oncol 112(1):9–16. doi:10.1016/j.radonc.2014.04.009

    Article  PubMed  Google Scholar 

  10. Nissen HD, Appelt AL (2013) Improved heart, lung and target dose with deep inspiration breath hold in a large clinical series of breast cancer patients. Radiother Oncol 106(1):28–32. doi:10.1016/j.radonc.2012.10.016

    Article  PubMed  Google Scholar 

  11. Bird BR, Swain SM (2008) Cardiac toxicity in breast cancer survivors: review of potential cardiac problems. Clin Cancer Res 14(1):14–24. doi:10.1158/1078-0432.CCR-07-1033

    Article  CAS  PubMed  Google Scholar 

  12. Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Bronnum D, Correa C, Cutter D, Gagliardi G, Gigante B, Jensen MB, Nisbet A, Peto R, Rahimi K, Taylor C, Hall P (2013) Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med 368(11):987–998. doi:10.1056/NEJMoa1209825

    Article  CAS  PubMed  Google Scholar 

  13. Taylor CW, Povall JM, McGale P, Nisbet A, Dodwell D, Smith JT, Darby SC (2008) Cardiac dose from tangential breast cancer radiotherapy in the year 2006. Int J Radiat Oncol Biol Phys 72(2):501–507. doi:10.1016/j.ijrobp.2007.12.058

    Article  PubMed  Google Scholar 

  14. Raggi P, Cooil B, Ratti C, Callister TQ, Budoff M (2005) Progression of coronary artery calcium and occurrence of myocardial infarction in patients with and without diabetes mellitus. Hypertension 46(1):238–243. doi:10.1161/01.HYP.0000164575.16609.02

    Article  CAS  PubMed  Google Scholar 

  15. Oudkerk M, Stillman AE, Halliburton SS, Kalender WA, Mohlenkamp S, McCollough CH, Vliegenthart R, Shaw LJ, Stanford W, Taylor AJ, van Ooijen PM, Wexler L, Raggi P, European Society of Cardiac R, North American Society for Cardiovascular I (2008) Coronary artery calcium screening: current status and recommendations from the European Society of Cardiac Radiology and North American Society for Cardiovascular Imaging. Eur Radiol 18 (12):2785–2807. doi:10.1007/s00330-008-1095-6

    Article  PubMed  Google Scholar 

  16. Kirsch J, Martinez F, Lopez D, Novaro GM, Asher CR (2016) National trends among radiologists in reporting coronary artery calcium in non-gated chest computed tomography. Int J Cardiovasc Imaging. doi:10.1007/s10554-016-0986-x

    PubMed  Google Scholar 

  17. Elias-Smale SE, Proenca RV, Koller MT, Kavousi M, van Rooij FJ, Hunink MG, Steyerberg EW, Hofman A, Oudkerk M, Witteman JC (2010) Coronary calcium score improves classification of coronary heart disease risk in the elderly: the Rotterdam study. J Am Coll Cardiol 56(17):1407–1414. doi:10.1016/j.jacc.2010.06.029

    Article  PubMed  Google Scholar 

  18. Yeboah J, McClelland RL, Polonsky TS, Burke GL, Sibley CT, O’Leary D, Carr JJ, Goff DC, Greenland P, Herrington DM (2012) Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. JAMA 308(8):788–795. doi:10.1001/jama.2012.9624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lee J (2011) Coronary artery calcium scoring and its impact on the clinical practice in the era of multidetector CT. Int J Cardiovasc Imaging 27(Suppl 1):9–25. doi:10.1007/s10554-011-9964-5

    Article  PubMed  Google Scholar 

  20. Greenland P, Alpert JS, Beller GA, Benjamin EJ, Budoff MJ, Fayad ZA, Foster E, Hlatky MA, Hodgson JM, Kushner FG, Lauer MS, Shaw LJ, Smith SC, Jr., Taylor AJ, Weintraub WS, Wenger NK, Jacobs AK, Smith SC, Jr., Anderson JL, Albert N, Buller CE, Creager MA, Ettinger SM, Guyton RA, Halperin JL, Hochman JS, Kushner FG, Nishimura R, Ohman EM, Page RL, Stevenson WG, Tarkington LG, Yancy CW, American College of Cardiology F, American Heart A (2010) 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 56 (25):e50–103. doi:10.1016/j.jacc.2010.09.001

    Article  PubMed  Google Scholar 

  21. Andratschke N, Maurer J, Molls M, Trott KR (2011) Late radiation-induced heart disease after radiotherapy. Clinical importance, radiobiological mechanisms and strategies of prevention. Radiother Oncol 100(2):160–166. doi:10.1016/j.radonc.2010.08.010

    Article  PubMed  Google Scholar 

  22. Sardaro A, Petruzzelli MF, D’Errico MP, Grimaldi L, Pili G, Portaluri M (2012) Radiation-induced cardiac damage in early left breast cancer patients: risk factors, biological mechanisms, radiobiology, and dosimetric constraints. Radiother Oncol 103(2):133–142. doi:10.1016/j.radonc.2012.02.008

    Article  PubMed  Google Scholar 

  23. Mylonas I, Alam M, Amily N, Small G, Chen L, Yam Y, Hibbert B, Chow BJ (2014) Quantifying coronary artery calcification from a contrast-enhanced cardiac computed tomography angiography study. Eur Heart J Cardiovasc Imaging 15(2):210–215. doi:10.1093/ehjci/jet144

    Article  PubMed  Google Scholar 

  24. Hecht HS, Budoff MJ, Berman DS, Ehrlich J, Rumberger JA (2006) Coronary artery calcium scanning: clinical paradigms for cardiac risk assessment and treatment. Am Heart J 151(6):1139–1146. doi:10.1016/j.ahj.2005.07.018

    Article  CAS  PubMed  Google Scholar 

  25. Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong JH, Wolmark N (2002) Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347(16):1233–1241. doi:10.1056/NEJMoa022152

    Article  PubMed  Google Scholar 

  26. van Dongen JA, Voogd AC, Fentiman IS, Legrand C, Sylvester RJ, Tong D, van der Schueren E, Helle PA, van Zijl K, Bartelink H (2000) Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst 92(14):1143–1150

    Article  PubMed  Google Scholar 

  27. Cushman M, Costantino JP, Tracy RP, Song K, Buckley L, Roberts JD, Krag DN (2001) Tamoxifen and cardiac risk factors in healthy women: suggestion of an anti-inflammatory effect. Arterioscler Thromb Vasc Biol 21(2):255–261

    Article  CAS  PubMed  Google Scholar 

  28. Aleman BM, van den Belt-Dusebout AW, De Bruin ML, van ‘t Veer MB, Baaijens MH, de Boer JP, Hart AA, Klokman WJ, Kuenen MA, Ouwens GM, Bartelink H, van Leeuwen FE (2007) Late cardiotoxicity after treatment for Hodgkin lymphoma. Blood 109(5):1878–1886. doi:10.1182/blood-2006-07-034405

    Article  CAS  PubMed  Google Scholar 

  29. Apter S, Shemesh J, Raanani P, Portnoy O, Thaler M, Zissin R, Ezra D, Rozenman J, Pfeffer R, Hertz M (2006) Cardiovascular calcifications after radiation therapy for Hodgkin lymphoma: computed tomography detection and clinical correlation. Coron Artery Dis 17(2):145–151

    Article  PubMed  Google Scholar 

  30. Chang M, Suh J, Kirtani V, Dobrescu A, Haas J, Zeldis S, Shayani S, Hindenburg AA (2013) Coronary calcium scanning in patients after adjuvant radiation for early breast cancer and ductal carcinoma in situ. Front Oncol 3:253. doi:10.3389/fonc.2013.00253

    Article  PubMed  PubMed Central  Google Scholar 

  31. Tjessem KH, Bosse G, Fossa K, Reinertsen KV, Fossa SD, Johansen S, Fossa A (2015) Coronary calcium score in 12-year breast cancer survivors after adjuvant radiotherapy with low to moderate heart exposure: relationship to cardiac radiation dose and cardiovascular risk factors. Radiother Oncol. doi:10.1016/j.radonc.2015.01.006

    PubMed  Google Scholar 

  32. Doyle JJ, Neugut AI, Jacobson JS, Wang J, McBride R, Grann A, Grann VR, Hershman D (2007) Radiation therapy, cardiac risk factors, and cardiac toxicity in early-stage breast cancer patients. Int J Radiat Oncol Biol Phys 68(1):82–93. doi:10.1016/j.ijrobp.2006.12.019

    Article  PubMed  Google Scholar 

  33. Hatoum OA, Otterson MF, Kopelman D, Miura H, Sukhotnik I, Larsen BT, Selle RM, Moulder JE, Gutterman DD (2006) Radiation induces endothelial dysfunction in murine intestinal arterioles via enhanced production of reactive oxygen species. Arterioscler Thromb Vasc Biol 26(2):287–294. doi:10.1161/01.ATV.0000198399.40584.8c

    Article  CAS  PubMed  Google Scholar 

  34. McEniery PT, Dorosti K, Schiavone WA, Pedrick TJ, Sheldon WC (1987) Clinical and angiographic features of coronary artery disease after chest irradiation. Am J Cardiol 60(13):1020–1024

    Article  CAS  PubMed  Google Scholar 

  35. Brosius FC 3rd, Waller BF, Roberts WC (1981) Radiation heart disease. Analysis of 16 young (aged 15 to 33 years) necropsy patients who received over 3,500 rads to the heart. Am J Med 70(3):519–530

    Article  PubMed  Google Scholar 

  36. Rutter CE, Chagpar AB, Evans SB (2014) Breast cancer laterality does not influence survival in a large modern cohort: implications for radiation-related cardiac mortality. Int J Radiat Oncol Biol Phys 90(2):329–334. doi:10.1016/j.ijrobp.2014.06.030

    Article  PubMed  Google Scholar 

  37. Soran O, Vargo JA, Polat AV, Soran A, Sumkin J, Beriwal S (2014) No association between left-breast radiation therapy or breast arterial calcification and long-term cardiac events in patients with breast cancer. J Womens Health 23(12):1005–1011. doi:10.1089/jwh.2014.4748

    Article  Google Scholar 

  38. Jacob S, Pathak A, Franck D, Latorzeff I, Jimenez G, Fondard O, Lapeyre M, Colombier D, Bruguiere E, Lairez O, Fontenel B, Milliat F, Tamarat R, Broggio D, Derreumaux S, Ducassou M, Ferrieres J, Laurier D, Benderitter M, Bernier MO (2016) Early detection and prediction of cardiotoxicity after radiation therapy for breast cancer: the BACCARAT prospective cohort study. Radiat Oncol 11:54. doi:10.1186/s13014-016-0627-5

    Article  PubMed  PubMed Central  Google Scholar 

  39. Budoff MJ, Nasir K, Kinney GL, Hokanson JE, Barr RG, Steiner R, Nath H, Lopez-Garcia C, Black-Shinn J, Casaburi R (2011) Coronary artery and thoracic calcium on noncontrast thoracic CT scans: comparison of ungated and gated examinations in patients from the COPD gene cohort. J Cardiovasc Comput Tomogr 5(2):113–118. doi:10.1016/j.jcct.2010.11.002

    Article  PubMed  Google Scholar 

  40. Kirsch J, Buitrago I, Mohammed TL, Gao T, Asher CR, Novaro GM (2012) Detection of coronary calcium during standard chest computed tomography correlates with multi-detector computed tomography coronary artery calcium score. Int J Cardiovasc Imaging 28(5):1249–1256. doi:10.1007/s10554-011-9928-9

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Cardiovascular Imaging, Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA

    Richard A. P. Takx, Rozemarijn Vliegenthart, U. Joseph Schoepf, Thomas Henzler & Paul Apfaltrer

  2. Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands

    Richard A. P. Takx

  3. Department of Radiology, University Medical Center Groningen, Center for Medical Imaging – North East Netherlands, University of Groningen, Groningen, The Netherlands

    Rozemarijn Vliegenthart

  4. Division of Cardiology, Department of Medicine, Medical University of South, Carolina, Charleston, SC, USA

    U. Joseph Schoepf & Pamela B. Morris

  5. Department of Biostatistics, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Lothar R. Pilz

  6. Institute of Clinical Radiology and Nuclear Medicine, University Medical Center, Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

    Stefan O. Schoenberg, Thomas Henzler & Paul Apfaltrer

  7. Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria

    Paul Apfaltrer

  8. Heart and Vascular Center, Medical University of South Carolina, Ashley River Tower, 25 Courtenay Drive, Charleston, SC, 29425-2260, USA

    U. Joseph Schoepf

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  1. Richard A. P. Takx
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Correspondence to U. Joseph Schoepf.

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Conflict of interest

Vliegenthart is supported by a grant from the Netherlands Organisation for Scientific Research. Schoepf is a consultant for and receives research support from Bayer, Bracco, GE Healthcare, Medrad, and Siemens. All other authors have nothing to disclose.

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Takx, R.A.P., Vliegenthart, R., Schoepf, U.J. et al. Coronary artery calcium in breast cancer survivors after radiation therapy. Int J Cardiovasc Imaging 33, 1425–1431 (2017). https://doi.org/10.1007/s10554-017-1119-x

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