Skip to main content

Advertisement

SpringerLink
Log in

Long-term follow-up for cardiovascular disease after chemotherapy and/or radiotherapy for breast cancer in an unselected population

  • Original Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Purpose

Whereas earlier research focused on specific patient groups, this study assessed the risk of cardiovascular disease (CVD) in an unselected population curatively treated for breast cancer (BC), compared with an age-matched random sample of controls.

Methods

Risks were determined in BC survivors and controls. CVD was divided into three categories: congestive heart failure, vascular cardiac diseases, and “other” cardiac diseases. Hazard ratios (HRs) and 95 % confidence intervals (95 % CI) adjusted for age, CVD, and CVD risk factors at baseline were determined by Cox regression analyses.

Results

All 561 survivors of BC experienced surgery of whom 229 received (neo)adjuvant radiotherapy, 145 received chemotherapy (with or without radiotherapy), and 187 received no adjuvant therapy. During follow-up (median 9; range 5–57 years), CVD occurred in 176/561 (31 %) survivors and in 398/1,635 (24 %) controls. After radiotherapy, no increased risks of congestive heart failure (HR 0.5; 95 % CI 0.2–1.8), vascular cardiac diseases (HR 1.1; 95 % CI 0.7–1.7), or other cardiac diseases (HR 1.3; 95 % CI 0.8–2.3) were found compared with controls. Similar results were found after chemotherapy for congestive heart failure (HR 1.8; 95 % CI 0.6–5.8), vascular cardiac diseases (HR 1.1; 95 % CI 0.5–2.3), and other cardiac diseases (HR 1.2; 95 % CI 0.3–5.5).

Conclusions

In an unselected population of BC survivors, no significant increased risk of CVD after radiotherapy and/or chemotherapy was found compared with controls. However, the HRs after chemotherapy were in-line with previous studies. Future studies should include more detailed information on treatment and more specific outcome measures.

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

Similar content being viewed by others

References

  1. La Vecchia C, Bosetti C, Lucchini F, Bertuccio P, Negri E, Boyle P, Levi F (2010) Cancer mortality in Europe, 2000–2004, and an overview of trends since 1975. Ann Oncol 21:1323–1360

    Article  PubMed  Google Scholar 

  2. Early Breast Cancer Trialists' Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717

    Article  Google Scholar 

  3. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) GLOBOCAN 2008: cancer incidence and mortality worldwide. International Agency for Research on Cancer, Lyon, France

    Google Scholar 

  4. 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 (CISNET) Collaborators (2005) Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med 353:1784–1792

    Article  CAS  PubMed  Google Scholar 

  5. DeMichele A, Putt M, Zhang Y, Glick JH, Norman S (2003) Older age predicts a decline in adjuvant chemotherapy recommendations for patients with breast carcinoma: evidence from a tertiary care cohort of chemotherapy-eligible patients. Cancer 97:2150–2159

    Article  PubMed  Google Scholar 

  6. Thomas GA, Leonard RC (2009) How age affects the biology of breast cancer. Clin Oncol (R Coll Radiol) 21:81–85

    Article  CAS  Google Scholar 

  7. Schimmel KJ, Richel DJ, van den Brink RB, Guchelaar HJ (2004) Cardiotoxicity of cytotoxic drugs. Cancer Treat Rev 30:181–191

    Article  CAS  PubMed  Google Scholar 

  8. Azim HA Jr, de Azambuja E, Colozza M, Bines J, Piccart MJ (2011) Long-term toxic effects of adjuvant chemotherapy in breast cancer. Ann Oncol 22:1939–1947

    Article  PubMed  Google Scholar 

  9. Early Breast Cancer Trialists' Collaborative Group (2002) Radiotherapy for early breast cancer. Cochrane Database Syst Rev 2, CD003647

    Google Scholar 

  10. Bird BR, Swain SM (2008) Cardiac toxicity in breast cancer survivors: review of potential cardiac problems. Clin Cancer Res 14:14–24

    Article  CAS  PubMed  Google Scholar 

  11. Harris EE (2008) Cardiac mortality and morbidity after breast cancer treatment. Cancer Control 15:120–129

    PubMed  Google Scholar 

  12. Lenihan DJ, Cardinale DM (2012) Late cardiac effects of cancer treatment. J Clin Oncol 30:3657–3664

    Article  PubMed  Google Scholar 

  13. Harris EE, Correa C, Hwang WT, Liao J, Litt HI, Ferrari VA, Solin LJ (2006) Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment. J Clin Oncol 24:4100–4106

    Article  PubMed  Google Scholar 

  14. 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 97:419–424

    Article  PubMed Central  PubMed  Google Scholar 

  15. Bouillon K, Haddy N, Delaloge S, Garbay JR, Garsi JP, Brindel P, Mousannif A, Le MG, Labbe M, Arriagada R, Jougla E, Chavaudra J, Diallo I, Rubino C, de Vathaire F (2011) Long-term cardiovascular mortality after radiotherapy for breast cancer. J Am Coll Cardiol 57:445–452

    Article  PubMed  Google Scholar 

  16. Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Correa C, McGale P, Taylor C, Wang Y, Clarke M, Davies C, Peto R, Bijker N, Solin L, Darby S (2010) Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast. J Natl Cancer Inst Monogr 2010:162–177

  17. 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 Group (EBCTCG) (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 366:2087–2106

    Article  CAS  PubMed  Google Scholar 

  18. Youssef G, Links M (2005) The prevention and management of cardiovascular complications of chemotherapy in patients with cancer. Am J Cardiovasc Drugs 5:233–243

    Article  CAS  PubMed  Google Scholar 

  19. Menna P, Salvatorelli E, Minotti G (2008) Cardiotoxicity of antitumor drugs. Chem Res Toxicol 21:978–989

    Article  CAS  PubMed  Google Scholar 

  20. Geiger S, Lange V, Suhl P, Heinemann V, Stemmler HJ (2010) Anticancer therapy induced cardiotoxicity: review of the literature. Anticancer Drugs 21:578–590

    Article  CAS  PubMed  Google Scholar 

  21. Elliott P (2006) Pathogenesis of cardiotoxicity induced by anthracyclines. Semin Oncol 33:S2–S7

    Article  CAS  PubMed  Google Scholar 

  22. Abu-Khalaf MM, Juneja V, Chung GG, DiGiovanna MP, Sipples R, McGurk M, Zelterman D, Haffty B, Reiss M, Wackers FJ, Lee FA, Burtness BA (2007) Long-term assessment of cardiac function after dose-dense and -intense sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) as adjuvant therapy for high risk breast cancer. Breast Cancer Res Treat 104:341–349

    Article  CAS  PubMed  Google Scholar 

  23. Du XL, Xia R, Liu CC, Cormier JN, Xing Y, Hardy D, Chan W, Burau K (2009) Cardiac toxicity associated with anthracycline-containing chemotherapy in older women with breast cancer. Cancer 115:5296–5308

    Article  PubMed  Google Scholar 

  24. Pinder MC, Duan Z, Goodwin JS, Hortobagyi GN, Giordano SH (2007) Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J Clin Oncol 25:3808–3815

    Article  CAS  PubMed  Google Scholar 

  25. Doyle JJ, Neugut AI, Jacobson JS, Grann VR, Hershman DL (2005) Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study. J Clin Oncol 23:8597–8605

    Article  PubMed  Google Scholar 

  26. Fumoleau P, Roche H, Kerbrat P, Bonneterre J, Romestaing P, Fargeot P, Namer M, Monnier A, Montcuquet P, Goudier MJ, Luporsi E, French Adjuvant Study Group (2006) Long-term cardiac toxicity after adjuvant epirubicin-based chemotherapy in early breast cancer: French Adjuvant Study Group results. Ann Oncol 17:85–92

    Article  CAS  PubMed  Google Scholar 

  27. Magne N, Largillier R, Marcy PY, Magne J, Namer M (2005) Cardiac toxicity assessment in locally advanced breast cancer treated neoadjuvantly with doxorubicin/paclitaxel regimen. Support Care Cancer 13:819–825

    Article  PubMed  Google Scholar 

  28. Shapiro CL, Hardenbergh PH, Gelman R, Blanks D, Hauptman P, Recht A, Hayes DF, Harris J, Henderson IC (1998) Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients. J Clin Oncol 16:3493–3501

    CAS  PubMed  Google Scholar 

  29. Sukel MP, Breekveldt-Postma NS, Erkens JA, van der Linden PD, Beiderbeck AB, Coebergh JW, Herings RM (2008) Incidence of cardiovascular events in breast cancer patients receiving chemotherapy in clinical practice. Pharmacoepidemiol Drug Saf 17:125–134

    Article  PubMed  Google Scholar 

  30. Faber MJ, Burgers JS, Westert GP (2012) A sustainable primary care system: lessons from the Netherlands. J Ambul Care Manage 35:174–181

    Article  PubMed  Google Scholar 

  31. Lamberts H, Wood M (1987) ICPC. International classification of primary care. Oxford University Press, London, UK

    Google Scholar 

  32. Hearnshaw H (2004) Comparison of requirements of research ethics committees in 11 European countries for a non-invasive interventional study. BMJ 328:140–141

    Article  PubMed Central  PubMed  Google Scholar 

  33. Jones JM, Ribeiro GG (1989) Mortality patterns over 34 years of breast cancer patients in a clinical trial of post-operative radiotherapy. Clin Radiol 40:204–208

    Article  CAS  PubMed  Google Scholar 

  34. Hooning MJ, Aleman BM, van Rosmalen AJ, Kuenen MA, Klijn JG, van Leeuwen FE (2006) Cause-specific mortality in long-term survivors of breast cancer: a 25-year follow-up study. Int J Radiat Oncol Biol Phys 64:1081–1091

    Article  PubMed  Google Scholar 

  35. Darby SC, McGale P, Taylor CW, Peto R (2005) Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries. Lancet Oncol 6:557–565

    Article  PubMed  Google Scholar 

  36. Paszat LF, Mackillop WJ, Groome PA, Boyd C, Schulze K, Holowaty E (1998) Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries. J Clin Oncol 16:2625–2631

    CAS  PubMed  Google Scholar 

  37. 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 368:987–998

    Article  CAS  PubMed  Google Scholar 

  38. 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 99:365–375

    Article  PubMed  Google Scholar 

  39. Pignol JP, Keller BM, Ravi A (2011) Doses to internal organs for various breast radiation techniques—implications on the risk of secondary cancers and cardiomyopathy. Radiat Oncol 6:5

    Article  PubMed Central  PubMed  Google Scholar 

  40. Marhin W, Wai E, Tyldesley S (2007) Impact of fraction size on cardiac mortality in women treated with tangential radiotherapy for localized breast cancer. Int J Radiat Oncol Biol Phys 69:483–489

    Article  PubMed  Google Scholar 

  41. Jansson T, Lindman H, Nygard K, Dahlgren CV, Montelius A, Oberg-Kreuger C, Asplund S, Bergh J (1998) Radiotherapy of breast cancer after breast-conserving surgery: an improved technique using mixed electron-photon beams with a multileaf collimator. Radiother Oncol 46:83–89

    Article  CAS  PubMed  Google Scholar 

  42. Nechuta S, Lu W, Zheng Y, Cai H, Bao PP, Gu K, Zheng W, Shu XO (2013) Comorbidities and breast cancer survival: a report from the Shanghai Breast Cancer Survival Study. Breast Cancer Res Treat 139(1):227–235

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Deng S, Wojnowski L (2007) Genotyping the risk of anthracycline-induced cardiotoxicity. Cardiovasc Toxicol 7:129–134

    Article  CAS  PubMed  Google Scholar 

  44. Mosterd A, Hoes AW, de Bruyne MC, Deckers JW, Linker DT, Hofman A, Grobbee DE (1999) Prevalence of heart failure and left ventricular dysfunction in the general population; the Rotterdam study. Eur Heart J 20:447–455

    Article  CAS  PubMed  Google Scholar 

  45. Cella D, Davis K, Breitbart W, Curt G, Coalition F (2001) Cancer-related fatigue: prevalence of proposed diagnostic criteria in a United States sample of cancer survivors. J Clin Oncol 19:3385–3391

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank all the general practitioners and other staff of the general practices for their cooperation. We also thank F. Groenhof, A.E. Oeloff, B.J. Swart, and L.D.G. Zwart for collecting the data.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of General Practice, University of Groningen, University Medical Center Groningen, P.O. Box 196, 9700 AD, Groningen, The Netherlands

    L. M. Boerman, A. J. Berendsen & M. Y. Berger

  2. Department of Epidemiology, University of Groningen, University Medical Center Groningen, P.O. Box 196, 9700 AD, Groningen, The Netherlands

    G. H. de Bock

  3. Department of Cardiology, University of Groningen, University Medical Center Groningen, P.O. Box 196, 9700 AD, Groningen, The Netherlands

    P. van der Meer

  4. Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, P.O. Box 196, 9700 AD, Groningen, The Netherlands

    J. H. Maduro

Authors
  1. L. M. Boerman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. J. Berendsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. van der Meer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. H. Maduro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Y. Berger
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. H. de Bock
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. H. de Bock.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Boerman, L.M., Berendsen, A.J., van der Meer, P. et al. Long-term follow-up for cardiovascular disease after chemotherapy and/or radiotherapy for breast cancer in an unselected population. Support Care Cancer 22, 1949–1958 (2014). https://doi.org/10.1007/s00520-014-2156-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-014-2156-9

Keywords

Search

Navigation