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Breast cancer radiotherapy and cardiac risk

Abstract

Breast cancer is the leading cause of morbidity and mortality in women in the developed world and its incidence in the developing world is on the rise. Management of breast cancer requires a multimodality approach and an integration of the services of surgery, radiation, and medical oncology. Radiotherapy after mastectomy or breast conservation leads to reduction in local recurrence by two-thirds. Recent trials and metaanalyses have also demonstrated overall survival benefit with radiotherapy. Of late, however, there has been concern regarding side effects of radiotherapy in breast cancer. Among these the cardiac risk has been particularly been of concern. This review discusses the etiology, manifestations, and evidence in relation to implication of breast cancer radiotherapy in cardiac adverse effects.

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References

  1. 1.

    Kamangar F, Dores GM, Anderson WF (2006) Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24(14):2137–2150

    PubMed  Article  Google Scholar 

  2. 2.

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

    PubMed  Article  Google Scholar 

  3. 3.

    Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, Aguilar M, Marubini E (2002) Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 347:1227–1232

    PubMed  Article  Google Scholar 

  4. 4.

    Truong PT, Olivotto IA, Whelan TJ, Levine M (2004) Clinical practice guidelines for the care, treatment of breast cancer. Clinical practice guidelines for the care, treatment of breast cancer: locoregional post-mastectomy radiotherapy. CMAJ 170(8):1263–1273

    PubMed  Google Scholar 

  5. 5.

    Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F (1997) Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. N Engl J Med 337:949–955

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Ragaz J, Jackson S, Le N (1997) Adjuvant radiotherapy, chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med 337:956

    CAS  PubMed  Article  Google Scholar 

  7. 7.

    Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans E, Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) et al (2005) Effects of radiotherapy, of differences in the extent of surgery for early breast cancer on local recurrence, 15-year survival: an overview of the randomised trials. Lancet 17(366):2087–2106

    Google Scholar 

  8. 8.

    Fajardo LF, Stewart JR, Cohn KE (1968) Morphology of radiation induced heart disease. Arch Pathol 86:512–519

    CAS  PubMed  Google Scholar 

  9. 9.

    Darby S, McGale P, Peto R, Granath F, Hall P, Akbom A (2003) Mortality from cardiovascular disease more than 10 years after radiotherapy for breast cancer: nationwide cohort study of 90000 Swedish women. BMJ 326:256–257

    PubMed  Article  Google Scholar 

  10. 10.

    Early Breast Cancer Trialists’ Collaborative Group (2000) Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials. Lancet 355:1757–1770

    Article  Google Scholar 

  11. 11.

    Fajardo LF, Stewart JR (1970) Experimental radiation-induced heart disease. Am J Pathol 59:299–316

    CAS  PubMed  Google Scholar 

  12. 12.

    Stewart JR, Fajardo LF (1971) Radiation-induced heart disease: clinical and experimental aspects. Radiol Clin North Am 9:511–531

    CAS  PubMed  Google Scholar 

  13. 13.

    Stewart JR, Fajardo LF, Gillette SM (1995) Radiation injury to the heart. Int J Radiat Oncol Biol Phys 31:1205–1211

    CAS  PubMed  Google Scholar 

  14. 14.

    Brosius FC, 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 70:519–530

    PubMed  Article  Google Scholar 

  15. 15.

    Bradley EW, Zook BC, Casarett GW (1988) Coronary arteriosclerosis and atherosclerosis in fast neutron or photon irradiated dogs. Int J Radiat Oncol Biol Phys 7:1103–1108

    Google Scholar 

  16. 16.

    Adams MJ, Lipshultz SE, Schwartz C (2003) Radiation-associated cardiovascular disease: manifestations and management. Semin Radiat Oncol 13:346–356

    PubMed  Article  Google Scholar 

  17. 17.

    Adams MJ, Hardenbergh PA, Constine L, Lipshultz SE (2003) Radiation-associated cardiovascular disease. Critical Rev Oncol Hemat 45:550–575

    Google Scholar 

  18. 18.

    Heidenreich PA, Hancock SL, Vagelos RH (2005) Diastolic dysfunction after mediastinal irradiation. Am Heart J 150:977–982

    PubMed  Article  Google Scholar 

  19. 19.

    Burns RJ, Bar Shlomo BZ, Druck MN (1983) Detection of radiation cardiomyopathy by gated radionuclide angiography. Am J Med 74:297–301

    CAS  PubMed  Article  Google Scholar 

  20. 20.

    Basavaraju SR, Easterly CE (2002) Pathophysiological effects of radiation on atherosclerosis development and progression, and the incidence of cardiovascular complications. Med Phys 29(10):2391–2403

    PubMed  Article  Google Scholar 

  21. 21.

    Aleman BM, van den Beit-Dusebout AW, Klokman WJ (2003) Long-term cause-specific mortality of patients treated for Hodgkin’s disease. J Clin Oncol 21:3431–3439

    PubMed  Article  Google Scholar 

  22. 22.

    Reinders JG, Heijmen BJ, Olofsen-van Acht MJ (1999) Ischemic heart disease after mantle field irradiation for Hodgkin’s disease in long-term follow-up. Radiother Oncol 51:35–42

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    O’Brien PJ (2007) Cardiac troponin is the most effective translational safety biomarker for myocardial injury in cardiotoxicity. Toxicology 245(3):206–218

    PubMed  Article  Google Scholar 

  24. 24.

    Chen HH, Burnett JC (1999) The natriuretic peptides in heart failure: diagnostic and therapeutic potentials. Proc Ass Am Phys 5:406–416

    Google Scholar 

  25. 25.

    Preston DL, Shimizu Y, Pierce DA et al (2003) Studies of mortality of atomic bomb survivors. Report 13: solid cancer and non-cancer disease mortality: 1950 –1997. Radiat Res 160:381–407

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Yamada M, Wong FL, Fujiwara S et al (2004) Non-cancer disease incidence in atomic bomb survivors, 1958–1998. Radiat Res 161:622–632

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Carr ZA, Land CE, Kleinermann RA (2005) Coronary heart disease after radiotherapy for peptic ulcer disease. Int J Radiat Oncol Biol Phys 61:842–850

    PubMed  Google Scholar 

  28. 28.

    Adams MJ, Lipsitz SR, Colan SD (2004) Cardiovascular status in long-term survivors of Hodgkin’s disease treated with chest radiotherapy. J Clin Oncol 22:3139–3148

    PubMed  Article  Google Scholar 

  29. 29.

    Senkus-Konefka E, Jassem J (2007) Cardiovascular effects of breast cancer radiotherapy. Cancer Treat Rev 33(6):578–593

    PubMed  Article  Google Scholar 

  30. 30.

    Gyenesa G, Rutqvistb LE, Liedbergb A, Fornander T (1998) Long-term cardiac morbidity and mortality in a randomized trial of pre- and postoperative radiation therapy versus surgery alone in primary breast cancer. Radiother Oncol 48:185–190

    Article  Google Scholar 

  31. 31.

    Haybittle JL, Brinkley D, Houghton J (1989) Postoperative radiotherapy and late mortality: evidence from the Cancer Research Campaign trial for early breast cancer. BMJ 298:1611–1614

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Højris I, Overgaard M, Christensen JJ, Overgaard J (1999) Morbidity and mortality of ischaemic heart disease in high-risk breast-cancer patients after adjuvant postmastectomy systemic treatment with or without radiotherapy: analysis of DBCG 82b and 82c randomised trials Radiotherapy Committee of the Danish Breast Cancer Cooperative Group. Lancet 354(9188):1425–1430

    PubMed  Article  Google Scholar 

  33. 33.

    Patt DA, Goodwin JS, Kuo Y-F, Freeman JL, Zhang DD, Buchholz TA, Hortobagyi GN, Giordano SH (2005) Cardiac morbidity of adjuvant radiotherapy for breast cancer. J Clin Oncol 23:7475–7482

    PubMed  Article  Google Scholar 

  34. 34.

    Jones B, Dale R (2003) The clinical radiobiology of high LET radiotherapy with particular reference to proton radiotherapy. Clin Oncol 15:S16–S22

    CAS  Article  Google Scholar 

  35. 35.

    Cox J (2007) Current and future status of proton-beam radiation therapy in radiation oncology. Clin Adv Hematol Oncol 5(4):303–305

    PubMed  Google Scholar 

  36. 36.

    Karger CP, Jäkel O (2007) Current status and new developments in ion therapy. Strahlenther Onkol 183(6):295–300

    PubMed  Article  Google Scholar 

  37. 37.

    Campana F, Kirova YM, Rosenwald JC (2005) Breast radiotherapy in the lateral decubitus position: a technique to prevent lung and heart irradiation. Int J Radiat Oncol Biol Phys 61:1348–1354

    PubMed  Google Scholar 

  38. 38.

    Griem KL, Fetherston P, Kuznetsova M (2003) Three-dimensional photon dosimetry: a comparison of treatment of the intact breast in the supine and prone position. Int J Radiat Oncol Biol Phys 57:891–899

    PubMed  Google Scholar 

  39. 39.

    Holland R, Veling SH, Mravunac M, Hendriks JH (1985) Histologic multifocality of Tis, T1-2 breast carcinomas. Implications for clinical trials of breast-conserving surgery. Cancer 56:979–990

    CAS  PubMed  Article  Google Scholar 

  40. 40.

    Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong J-H, 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 347:1233–1241

    PubMed  Article  Google Scholar 

  41. 41.

    Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, Aguilar M, Marubini E (2002) Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 347:1227–1232

    PubMed  Article  Google Scholar 

  42. 42.

    McIntosh A, Read PW, Khandelwal SR, Arthur DW, Turner AB, Ruchala KJ, Olivera GH, Jeswani S, Sheng K (2008) Evaluation of coplanar partial left breast irradiation using tomotherapy-based topotherapy. Int J Radiat Oncol Biol Phys 71(2):603–610

    PubMed  Google Scholar 

  43. 43.

    McDonald MW, Godette KD, Butker EK, Davis LW, Johnstone PA (2008) Long-term outcomes of IMRT for breast cancer: a single-institution cohort analysis. Int J Radiat Oncol Biol Phys 72:1031–1040

    PubMed  Google Scholar 

  44. 44.

    Bush DA, Slater JD, Garberoglio C, Yuh G, Hocko JM, Slater JM (2007) A technique of partial breast irradiation utilizing proton beam radiotherapy: comparison with conformal X-ray therapy. Cancer J 13(2):114–118

    PubMed  Article  Google Scholar 

  45. 45.

    Recht A (2006) Which breast cancer patients should really worry about radiation-induced heart disease—and how much? J Clin Oncol 1:4059–4061

    Google Scholar 

  46. 46.

    Herceptin Adjuvant (HERA) Trial Study Team (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353(16):1659–1672

    Article  Google Scholar 

  47. 47.

    Telli ML, Hunt SA, Carlson RW, Guardino AE (2007) Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility. J Clin Oncol 25(23):3525–3533

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    Prosnitz RG, Hubbs JL, Evans ES, Zhou SM, Yu X, Blazing MA, Hollis DR, Tisch A, Wong TZ, Borges-Neto S, Hardenbergh PH, Marks LB (2007) Prospective assessment of radiotherapy-associated cardiac toxicity in breast cancer patients: analysis of data 3 to 6 years after treatment. Cancer 110(8):1840–1850

    PubMed  Article  Google Scholar 

  49. 49.

    Hardenbergh PH, Munley MT, Bentel GC (2001) Cardiac perfusion changes in patients treated for breast cancer with radiation therapy and doxorubicin: preliminary results. Int J Radiat Oncol Biol Phys 49:1023–1028

    CAS  PubMed  Google Scholar 

  50. 50.

    Fornander GT, Carlens P, Glas U, Rutqvist LE (1996) Myocardial damage in breast cancer patients treated with adjuvant radiotherapy: a prospective study. Int J Radiat Oncol Biol Phys 36:899–905

    PubMed  Google Scholar 

  51. 51.

    Munshi A (2007) Breast cancer radiotherapy and cardiac risk: the 15-year paradox!. J Cancer Res Ther 3:190–192

    PubMed  Article  Google Scholar 

  52. 52.

    Munshi A, Budrukkar A (2007) Hypofractionated radiation therapy in breast cancer: a revolutionary breakthrough or a long way to go? J Clin Oncol 25:458–459

    PubMed  Article  Google Scholar 

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Correspondence to Anusheel Munshi.

Additional information

Search strategy: The search engines used for the review were Pubmed, Google and Yahoo. Published data for this review were identified by systematically searching all trials, review articles and metaanalyses between 1960 and 2009 in the PubMed-MedLine restricted to the English language from 1980 till date with the following Me dical S ubject H eading (MeSH) terms: “breast cancer”; “radiotherapy”; “cardiac risk” using BOOLEAN search algorithms.

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Munshi, A., Talapatra, K. & Dutta, D. Breast cancer radiotherapy and cardiac risk. Oncol Rev 4, 137–146 (2010). https://doi.org/10.1007/s12156-010-0041-4

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Keywords

  • Radiotherapy
  • Cardiac toxicity
  • Breast