Skip to main content

Advertisement

SpringerLink
Log in

Examining the cost-effectiveness of baseline left ventricular function assessment among breast cancer patients undergoing anthracycline-based therapy

  • Review
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Background

There is a lack of consensus to guide which breast cancer patients require left ventricular function assessment (LVEF) prior to anthracycline therapy; the cost-effectiveness of screening this patient population has not been previously evaluated.

Methods

We performed a retrospective analysis of the Yale Nuclear Cardiology Database, including 702 patients with baseline equilibrium radionuclide angiography (ERNA) scan prior to anthracycline and/or trastuzumab therapy. We sought to examine associations between abnormal baseline LVEF and potential cardiac risk factors. Additionally, we designed a Markov model to determine the incremental cost-effectiveness ratio (ICER) of ERNA screening for women aged 55 with stage I–III breast cancer from a payer perspective over a lifetime horizon.

Results

An abnormal LVEF was observed in 2% (n = 14) of patients. There were no significant associations on multivariate analysis performed on self-reported risk factors. Our analysis showed LVEF screening is cost-effective with ICER of $45,473 per QALY gained. For a willingness-to-pay threshold of $100,000/ QALY, LVEF screening had an 81.9% probability of being cost-effective. Under the same threshold, screening was cost-effective for non-anthracycline cardiotoxicity risk of RR ≤ 0.58, as compared to anthracycline regimens.

Conclusions

Age, preexisting cardiac risk factors and coronary artery disease did not predict a baseline abnormal LVEF. While the prevalence of an abnormal baseline LVEF is low in patients with breast cancer, our results suggest that cardiac screening prior to anthracycline is cost-effective.

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. 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(16):1659–1672. https://doi.org/10.1056/NEJMoa052306

    Article  CAS  PubMed  Google Scholar 

  2. Tan-Chiu E, Yothers G, Romond E et al (2005) Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2–overexpressing breast cancer: NSABP B-31. J Clin Oncol 23(31):7811–7819. https://doi.org/10.1200/JCO.2005.02.4091

    Article  CAS  PubMed  Google Scholar 

  3. Bria E, Cuppone F, Fornier M et al (2008) Cardiotoxicity and incidence of brain metastases after adjuvant trastuzumab for early breast cancer: the dark side of the moon? A meta-analysis of the randomized trials. Breast Cancer Res Treat 109(2):231–239. https://doi.org/10.1007/s10549-007-9663-z

    Article  CAS  PubMed  Google Scholar 

  4. Russell SD, Blackwell KL, Lawrence J et al (2010) Independent adjudication of symptomatic heart failure with the use of doxorubicin and cyclophosphamide followed by trastuzumab adjuvant therapy: a combined review of cardiac data from the national surgical adjuvant breast and bowel project B-31 and the North Central cancer treatment group N9831 clinical trials. J Clin Oncol 28(21):3416–3421. https://doi.org/10.1200/JCO.2009.23.6950

    Article  CAS  PubMed  Google Scholar 

  5. Procter M, Suter TM, de Azambuja E et al (2010) Longer-term assessment of trastuzumab-related cardiac adverse events in the herceptin adjuvant (HERA) trial. J Clin Oncol 28(21):3422–3428. https://doi.org/10.1200/JCO.2009.26.0463

    Article  PubMed  Google Scholar 

  6. Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353(16):1673–1684. https://doi.org/10.1056/NEJMoa052122

    Article  CAS  Google Scholar 

  7. Perez EA, Suman VJ, Davidson NE et al (2008) Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or Without trastuzumab in the north central cancer treatment group N9831 adjuvant breast cancer trial. J Clin Oncol 26(8):1231–1238. https://doi.org/10.1200/JCO.2007.13.5467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Jones S, Holmes FA, O’Shaughnessy J et al (2009) Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US oncology research trial 9735. J Clin Oncol 27(8):1177–1183. https://doi.org/10.1200/JCO.2008.18.4028

    Article  CAS  PubMed  Google Scholar 

  9. Smith I, Procter M, Gelber RD et al (2007) 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369(9555):29–36. https://doi.org/10.1016/S0140-6736(07)60028-2

    Article  CAS  Google Scholar 

  10. Slamon D, Eiermann W, Robert N et al (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365(14):1273–1283. https://doi.org/10.1056/NEJMoa0910383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Perez EA, Romond EH, Suman VJ et al (2011) Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2–positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol 29(25):3366–3373. https://doi.org/10.1200/JCO.2011.35.0868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Perez EA, Suman VJ, Davidson NE et al (2011) Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J Clin Oncol 29(34):4491–4497. https://doi.org/10.1200/JCO.2011.36.7045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tarantini L, Gori S, Faggiano P et al (2012) Adjuvant trastuzumab cardiotoxicity in patients over 60 years of age with early breast cancer: a multicenter cohort analysis. Ann Oncol 23(12):3058–3063. https://doi.org/10.1093/annonc/mds127

    Article  CAS  PubMed  Google Scholar 

  14. Chen J, Long JB, Hurria A, Owusu C, Steingart RM, Gross CP (2012) Incidence of heart failure or cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Coll Cardiol 60(24):2504–2512. https://doi.org/10.1016/j.jacc.2012.07.068

    Article  CAS  PubMed  Google Scholar 

  15. Fox KF (2006) The evaluation of left ventricular function for patients being considered for, or receiving Trastuzumab (Herceptin) therapy. Br J Cancer 95(10):1454. https://doi.org/10.1038/sj.bjc.6603340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Smith LA, Cornelius VR, Plummer CJ et al (2010) Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials. BMC Cancer 10(1):337. https://doi.org/10.1186/1471-2407-10-337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Swain SM, Whaley FS, Ewer MS (2003) Congestive heart failure in patients treated with doxorubicin. Cancer 97(11):2869–2879. https://doi.org/10.1002/cncr.11407

    Article  CAS  Google Scholar 

  18. 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(25):3808–3815. https://doi.org/10.1200/JCO.2006.10.4976

    Article  CAS  PubMed  Google Scholar 

  19. Alexander J, Dainiak N, Berger HJ et al (1979) Serial assessment of doxorubicin cardiotoxicity with quantitative radionuclide angiocardiography. N Engl J Med 300(6):278–283. https://doi.org/10.1056/NEJM197902083000603

    Article  CAS  PubMed  Google Scholar 

  20. Ritchie JL, Singer JW, Thorning D, Sorensen SG, Hamilton GW (1980) Anthracycline cardiotoxicity: clinical and pathologic outcomes assessed by radionuclide ejection fraction. Cancer 46(5):1109–1116. https://doi.org/10.1002/1097-0142(19800901)46:5%3C1109::AID-CNCR2820460506%3E3.0.CO;2-B.

    Article  CAS  PubMed  Google Scholar 

  21. Zamar D, McNeney B, Graham J (2007) elrm: software implementing exact-like inference for logistic regression models. J Stat Softw. https://doi.org/10.18637/jss.v021.i03

    Article  Google Scholar 

  22. Go AS, Mozaffarian D, Roger VL et al (2013) Heart disease and stroke statistics–2013 update: a report from the American Heart Association. Circulation 127(1):e6–e245. https://doi.org/10.1161/CIR.0b013e31828124ad

    Article  PubMed  Google Scholar 

  23. Swain SM, Tang G, Geyer CE et al (2013) Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol 31(26):3197–3204. https://doi.org/10.1200/JCO.2012.48.1275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Blum JL, Flynn PJ, Yothers G et al (2016) Interim joint analysis of the ABC (anthracyclines in early breast cancer) phase III trials (USOR 06–090, NSABP B-46I/USOR 07132, NSABP B-49 [NRG Oncology]) comparing docetaxel + cyclophosphamide (TC) v anthracycline/taxane-based chemotherapy regimens (Tax. J Clin Oncol 34(15_suppl):1000. https://doi.org/10.1200/JCO.2016.34.15_suppl.1000

    Article  Google Scholar 

  25. Investigators* TS (1992) Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 327(10):685–691. https://doi.org/10.1056/NEJM199209033271003

    Article  Google Scholar 

  26. Ryberg M, Nielsen D, Skovsgaard T, Hansen J, Jensen BV, Dombernowsky P (1998) Epirubicin cardiotoxicity: an analysis of 469 patients with metastatic breast cancer. J Clin Oncol 16(11):3502–3508. https://doi.org/10.1200/JCO.1998.16.11.3502

    Article  CAS  PubMed  Google Scholar 

  27. Bowles EJA, Wellman R, Feigelson HS et al (2012) Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. JNCI J Natl Cancer Inst 104(17):1293–1305. https://doi.org/10.1093/jnci/djs317

    Article  CAS  PubMed  Google Scholar 

  28. Levy WC, Mozaffarian D, Linker DT et al (2006) The seattle heart failure model: prediction of survival in heart failure. Circulation 113(11):1424–1433. https://doi.org/10.1161/CIRCULATIONAHA.105.584102

    Article  PubMed  Google Scholar 

  29. Cancer Statistics SEER Review 1975–2005—Previous version—SEER cancer statistics. https://seer.cancer.gov/archive/csr/1975_2005/. Accessed December 25, 2017

  30. Arias E, Curtin LR, Wei R, Anderson RN (2008) National vital statistics reports 57(1). https://www.cdc.gov/nchs/data/nvsr/nvsr57/nvsr57_01.pdf. Accessed 25 Dec 2017

  31. Leung PP, Tannock IF, Oza AM, Puodziunas A, Dranitsaris G (1999) Cost-utility analysis of chemotherapy using paclitaxel, docetaxel, or vinorelbine for patients with anthracycline-resistant breast cancer. J Clin Oncol 17(10):3082–3090. https://doi.org/10.1200/JCO.1999.17.10.3082

    Article  CAS  PubMed  Google Scholar 

  32. Kruse GB, Amonkar MM, Smith G, Skonieczny DC, Stavrakas S (2008) Analysis of costs associated with administration of intravenous single-drug therapies in metastatic breast cancer in a U.S. population. J Manag Care Pharm 14(9):844–857. https://doi.org/10.18553/jmcp.2008.14.9.844

    Article  PubMed  Google Scholar 

  33. Rao S, Kubisiak J, Gilden D (2004) Cost of illness associated with metastatic breast cancer. Breast Cancer Res Treat 83(1):25–32. https://doi.org/10.1023/B:BREA.0000010689.55559.06

    Article  CAS  PubMed  Google Scholar 

  34. Dunlay SM, Shah ND, Shi Q et al (2011) Lifetime costs of medical care after heart failure diagnosis. Circ Cardiovasc Qual Outcomes 4(1):68–75. https://doi.org/10.1161/CIRCOUTCOMES.110.957225

    Article  PubMed  Google Scholar 

  35. Barlow WE (2009) Overview of methods to estimate the medical costs of cancer. Med Care 47(7 Suppl 1):S33–S36. https://doi.org/10.1097/MLR.0b013e3181a2d847

    Article  PubMed  PubMed Central  Google Scholar 

  36. Mandelblatt JS, Schechter CB, Yabroff KR et al (2005) Toward optimal screening strategies for older women. Costs, benefits, and harms of breast cancer screening by age, biology, and health status. J Gen Intern Med 20(6):487–496. https://doi.org/10.1111/j.1525-1497.2005.0116.x

    Article  PubMed  PubMed Central  Google Scholar 

  37. Wong FL, Bhatia S, Landier W et al (2014) Cost-effectiveness of the children’s oncology group long-term follow-up screening guidelines for childhood cancer survivors at risk for treatment-related heart failure. Ann Intern Med 160(10):672. https://doi.org/10.7326/M13-2498

    Article  PubMed  PubMed Central  Google Scholar 

  38. Lee JM, McMahon PM, Kong CY et al (2010) Cost-effectiveness of breast MR imaging and screen-film mammography for screening BRCA1 gene mutation carriers. Radiology 254(3):793–800. https://doi.org/10.1148/radiol.09091086

    Article  PubMed  PubMed Central  Google Scholar 

  39. Reed SD, Li Y, Dunlap ME et al (2012) In-hospital resource use and medical costs in the last year of life by mode of death (from the HF-ACTION randomized controlled trial). Am J Cardiol 110(8):1150–1155. https://doi.org/10.1016/J.AMJCARD.2012.05.059

    Article  PubMed  PubMed Central  Google Scholar 

  40. Levinsky NG, Yu W, Ash A et al (2001) Influence of age on medicare expenditures and medical care in the last year of life. JAMA 286(11):1349–1355. http://www.ncbi.nlm.nih.gov/pubmed/11560540. Accessed 25 Dec 2017

  41. Folland S, Goodman AC, Stano M. The Economics of Health and Health Care. http://www.ssu.ac.ir/cms/fileadmin/user_upload/Daneshkadaha/dbehdasht/modiryat_khatamat_behdashti/kotob_farsi/The_economics_of_health_and_health_care-_Sherman_Folland.pdf. Accessed 25 Dec 2017

  42. Stout NK, Rosenberg MA, Trentham-Dietz A, Smith MA, Robinson SM, Fryback DG (2006) Retrospective cost-effectiveness analysis of screening mammography. JNCI J Natl Cancer Inst 98(11):774–782. https://doi.org/10.1093/jnci/djj210

    Article  PubMed  Google Scholar 

  43. Fryback DG, Dasbach EJ, Klein R et al (1993) The Beaver dam health outcomes study. Med Decis Mak 13(2):89–102. https://doi.org/10.1177/0272989X9301300202

    Article  CAS  Google Scholar 

  44. Wang S-Y, Hsu SH, Gross CP et al (2016) Association between time since cancer diagnosis and health-related quality of life: a population-level analysis. Value Health 19(5):631–638. https://doi.org/10.1016/j.jval.2016.02.010

    Article  PubMed  PubMed Central  Google Scholar 

  45. Gold MR (1996) Cost-effectiveness in health and medicine. Oxford University Press, Oxford

    Google Scholar 

  46. Briggs AH, Goeree R, Blackhouse G, O’Brien BJ (2002) Probabilistic analysis of cost-effectiveness models: choosing between treatment strategies for gastroesophageal reflux disease. Med Decis Mak 22(4):290–308. https://doi.org/10.1177/0272989X0202200408

    Article  Google Scholar 

  47. Mina A, Rafei H, Khalil M, Hassoun Y, Nasser Z, Tfayli A (2015) Role of baseline echocardiography prior to initiation of anthracycline-based chemotherapy in breast cancer patients. BMC Cancer 15(1):10. https://doi.org/10.1186/s12885-014-1004-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Truong SR, Barry WT, Moslehi JJ, Baker EL, Mayer EL, Partridge AH (2016) Evaluating the utility of baseline cardiac function screening in early-stage breast cancer treatment. Oncologist 21(6):666–670. https://doi.org/10.1634/theoncologist.2015-0449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Cheitlin MD, Armstrong WF, Aurigemma GP et al (2003) ACC/AHA/ASE 2003 guideline update for the clinical application of echocardiography: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography). Circulation 108(9):1146–1162. https://doi.org/10.1161/01.CIR.0000073597.57414.A9

    Article  PubMed  Google Scholar 

  50. Klocke FJ, Baird MG, Lorell BH et al (2003) ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging–executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). J Am Coll Cardiol 42(7):1318–1333. http://www.ncbi.nlm.nih.gov/pubmed/14522503. Accessed 25 Dec 2017

  51. Sabel MS, Levine EG, Hurd T et al (2001) Is MUGA scan necessary in patients with low-risk breast cancer before doxorubicin-based adjuvant therapy? Multiple gated acquisition. Am J Clin Oncol 24(4):425–428. http://www.ncbi.nlm.nih.gov/pubmed/11474280. Accessed 25 Dec 2017

  52. Porea TJ, Dreyer ZE, Bricker JT, Mahoney DH (2001) Evaluation of left ventricular function in asymptomatic children about to undergo anthracycline-based chemotherapy for acute leukemia: an outcome study. J Pediatr Hematol Oncol 23(7):420–423. http://www.ncbi.nlm.nih.gov/pubmed/11878575. Accessed 25 Dec 2017

  53. Jeyakumar A, DiPenta J, Snow S et al (2012) Routine cardiac evaluation in patients with early-stage breast cancer before adjuvant chemotherapy. Clin Breast Cancer 12(1):4–9. https://doi.org/10.1016/j.clbc.2011.07.006

    Article  PubMed  Google Scholar 

  54. van Royen N, Jaffe CC, Krumholz HM et al (1996) Comparison and reproducibility of visual echocardiographic and quantitative radionuclide left ventricular ejection fractions. Am J Cardiol 77(10):843–850. http://www.ncbi.nlm.nih.gov/pubmed/8623737. Accessed 25 Dec 2017

Download references

Author information

Authors and Affiliations

  1. Section of Solid Tumors, Sidney Kimmel Cancer Center, Thomas Jefferson University, 1025 Walnut Street, 7th Floor, Philadelphia, PA, 19107, USA

    Maysa M. Abu-Khalaf

  2. Hospital of University of Pennsylvania, Philadelphia, PA, USA

    Anton Safonov

  3. Stamford Health, Stamford, CT, USA

    Jamie Stratton

  4. Yale University School of Public Health, New Haven, CT, USA

    Shiyi Wang

  5. Section of Medical Oncology, Yale University School of Medicine, New Haven, CT, USA

    Christos Hatzis & Lajos Pusztai

  6. Diagnostic Radiology Department, UCLA, Los Angeles, CA, USA

    Esther Park

  7. Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale University School of Medicine, New Haven, CT, USA

    Shiyi Wang & Cary P. Gross

  8. Cardiovascular Institute of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI, USA

    Raymond Russell

Authors
  1. Maysa M. Abu-Khalaf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anton Safonov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jamie Stratton
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shiyi Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christos Hatzis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Esther Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lajos Pusztai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Cary P. Gross
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Raymond Russell
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MA-K: conceptualization, data curation, methodology, project administration, resources, supervision, writing; AS: formal analysis, methodology, visualization, writing; JS: data curation, formal analysis, methodology, visualization, writing; SW: data curation, formal analysis, methodology, visualization, writing; CH: conceptualization, formal analysis, writing, Esther Park – data curation, formal analysis; LP: methodology, supervision, writing; CG: methodology, supervision, writing; RR: conceptualization, supervision, project administration, writing.

Corresponding author

Correspondence to Maysa M. Abu-Khalaf.

Ethics declarations

Conflict of interest

Maysa M. Abu-Khalaf MD: Received honorarium for a Consultant/Advisory role from AstraZeneca, Immunomedics, PUMA, Biothera and Agendia. Received a research grant from Novartis for an investigator-initiated clinical trial. Christos Hatzis PhD: Received remuneration from Bristol-Myers Squibb. Lajos Pusztai MD DPhil: Received honorarium for a Consultant/Advisory role from Merck, Astrazeneca, Novartis, Seattle Genetics, Pfizer, and Almac: received research funding from Merck, AstraZeneca, and Seattle Genetics. Cary P. Gross MD: Received remuneration/Travel funding from Flatiron Health and received research funding from Johnson &Johnson and NCCN/Pfizer. Raymond Russell MD, PhD: Spouse employed by ResTORbio. Spouse receives stock options from ResTORbio. All other authors declared that they have 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.

Informed consent

Informed consent was waived by institutional review board for this retrospective review study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PNG 111 KB)

Supplementary material 2 (TIF 80 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abu-Khalaf, M.M., Safonov, A., Stratton, J. et al. Examining the cost-effectiveness of baseline left ventricular function assessment among breast cancer patients undergoing anthracycline-based therapy. Breast Cancer Res Treat 176, 261–270 (2019). https://doi.org/10.1007/s10549-019-05178-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-019-05178-z

Keywords

Search

Navigation