Breast Cancer Research and Treatment

, Volume 109, Issue 3, pp 559–566 | Cite as

The model-based cost-effectiveness analysis of 1-year adjuvant trastuzumab treatment: based on 2-year follow-up HERA trial data

  • Takeru Shiroiwa
  • Takashi Fukuda
  • Kojiro Shimozuma
  • Yasuo Ohashi
  • Kiichiro Tsutani


Background Several randomized controlled trials have confirmed the usefulness of trastuzumab as an adjuvant therapy for HER2-overexpressed breast cancer patients; however, the costs for 1-year treatment are high. Therefore, we performed an economic analysis regarding the efficient distribution of medical resources. Methods To analyze the cost-effectiveness for a 1-year adjuvant trastuzumab treatment group compared with the observation group, we constructed a Markov model adopting a 3% per year discount rate for costs and outcomes. The time horizon was 50 years. The perspective was that of health-care payers, as only direct medical costs were calculated. The outcome was measured as life-year gained (LYG) from 2-year follow-up HERA trial data. Results The ICER of the standard setting (5 years efficacy and 50–60 kg patient weight) was JPY 2,600,000 (€17,000) per LYG. The calculation results of other weight class ICER were JPY 2,200,000 (€15,000) and JPY 3,300,000 (€22,000) per LYG for the patients, respectively, who weighed less than 50 kg, and 60–75 kg. In the sensitivity analysis, the period of trastuzumab efficacy was the most influential parameter for the result of cost-effectiveness. However, even if the trastuzumab efficacy were to continue for only 2 years, at least, which is a conservative setting judging from the joint analysis (NSABP B-31 and NCCTG N9831 trials), the ICER remains acceptable for any weight class. Conclusion These results suggest that the 1-year adjuvant trastuzumab treatment is cost-effective. Both clinical and economic benefits were superior for the 1-year adjuvant trastuzumab treatment group compared with the observation group.


Adjuvant treatment Breast cancer Cost-effectiveness HERA trial Trastuzumab 



This study was performed as the Comprehensive Support Project for Health Outcomes Research project (CSP-HOR) established by the Public Health Research Foundation (PHRF). We thank the PHRF for the grant supporting our study.


  1. 1.
    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 365:1687–1717CrossRefGoogle Scholar
  2. 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 235:177–182PubMedCrossRefGoogle Scholar
  3. 3.
    Slamon DJ, Leyland-Jones B, Shak S et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792PubMedCrossRefGoogle Scholar
  4. 4.
    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 23:4265–4274PubMedCrossRefGoogle Scholar
  5. 5.
    Osoba D, Slamon DJ, Burchmore M et al (2002) Effects on quality of life of combined trastuzumab and chemotherapy in women with metastatic breast cancer. J Clin Oncol 20:3106–3113PubMedCrossRefGoogle Scholar
  6. 6.
    Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672PubMedCrossRefGoogle Scholar
  7. 7.
    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 369:29–36PubMedCrossRefGoogle Scholar
  8. 8.
    Romond EH, Perez EA, Bryant J et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684PubMedCrossRefGoogle Scholar
  9. 9.
    Slamon D, Eiermann W, Robert N et al (2006) BCIRG 006: 2nd interim analysis phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC→T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC→TH) with docetaxel, carboplatin and trastuzumab (TCH) in Her2 neu positive early breast cancer patients. Breast Cancer Res Treat 100(Sup.1):abstr 52Google Scholar
  10. 10.
    National Institute for Health and Clinical Excellence (2006) Trastuzumab for the adjuvant treatment of early-stage HER2-positive breast cancer.Google Scholar
  11. 11.
    Weinstein MC, Siegel JE, Gold MR et al (1996) Recommendations of the panel on cost-effectiveness in health and medicine. JAMA 276:1253–1258PubMedCrossRefGoogle Scholar
  12. 12.
    Ewer MS, Vooletich MT, Durand JB et al (2005) Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol 23:7820–7826PubMedCrossRefGoogle Scholar
  13. 13.
    Suter TM, Cook-Bruns N, Barton C (2004) Cardiotoxicity associated with trastuzumab (Herceptin) therapy in the treatment of metastatic breast cancer. Breast 13:173–183PubMedCrossRefGoogle Scholar
  14. 14.
    Hortobagyi GN (1998) Treatment of breast cancer. N Engl J Med 339:974–984PubMedCrossRefGoogle Scholar
  15. 15.
    Mouridsen H, Gershanovich M, Sun Y et al (2001) Superior efficacy of Letrozole versus Tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the international Letrozole breast cancer group. J Clin Oncol 19:2596–2606PubMedGoogle Scholar
  16. 16.
    Klijn JG, Blamey RW, Boccardo F et al (2001) Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four randomized trials. J Clin Oncol 19:343–353PubMedGoogle Scholar
  17. 17.
    Toi M, Saeki T, Aogi K et al (2005) Late phase II clinical study of vinorelbine monotherapy in advanced or recurrent breast cancer previously treated with anthracyclines and taxanes. Jpn J Clin Oncol 35:310–315PubMedCrossRefGoogle Scholar
  18. 18.
    Fumoleau P, Largillier R, Clippe C et al (2004) Multicentre, phase II study evaluating capecitabine monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer. Eur J Cancer 40:536–542PubMedCrossRefGoogle Scholar
  19. 19.
    Le MG, Arriagada R, Spielmann M et al (2002) Prognostic factors for death after an isolated local recurrence in patients with early-stage breast cancer. Cancer 94:2813–2820PubMedCrossRefGoogle Scholar
  20. 20.
    Briggs A (2001) Handling uncertainty in economic evaluation and presenting the results. In: Drummond M, McGuire A (eds) Economic evaluation in health care: merging theory with practice. Oxford university press, OxfordGoogle Scholar
  21. 21.
    Smith TJ, Davidson NE, Schapira DV et al (1999) American Society of Clinical Oncology 1998 update of recommended breast cancer surveillance guidelines. J Clin Oncol 17:1080–1082PubMedGoogle Scholar
  22. 22.
    Kris MG, Hesketh PJ, Somerfield MR et al (2006) American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 24:2932–2947PubMedCrossRefGoogle Scholar
  23. 23.
    National Institute for Health and Clinical Excellence (2002) Guidance on the use of trastuzumab for the treatment of advanced breast cancerGoogle Scholar
  24. 24.
    Liberato NL, Marchetti M, Barosi G (2007) Cost effectiveness of adjuvant trastuzumab in human epidermal growth factor receptor 2—positive breast cancer. J Clin Oncol 25:625–633PubMedCrossRefGoogle Scholar
  25. 25.
    Kurian AW, Thompson RN, Gaw AF et al (2007) A cost-effectiveness analysis of adjuvant trastuzumab regimens in early HER2/neu—positive breast cancer. J Clin Oncol 25:634–641PubMedCrossRefGoogle Scholar
  26. 26.
    Tammy TO (2004) Cost-effectiveness versus cost-utility analysis of interventions for cancer: does adjusting for health-related quality of life really matter? Value in Health 7:70–78CrossRefGoogle Scholar
  27. 27.
    Joensuu H, Kellokumpu-Lehtinen PL, Bono P et al (2006) Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med 354:809–820PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Takeru Shiroiwa
    • 1
  • Takashi Fukuda
    • 1
  • Kojiro Shimozuma
    • 2
  • Yasuo Ohashi
    • 3
  • Kiichiro Tsutani
    • 1
  1. 1.Department of Drug Policy and Management, Graduate School of Pharmaceutical SciencesThe University of TokyoTokyoJapan
  2. 2.Department of Healthcare and Social ServicesUniversity of Marketing and Distribution SciencesKobeJapan
  3. 3.Department of Biostatistics/Epidemiology and Preventive Health Sciences, Graduate School of Health Sciences and NursingThe University of TokyoTokyoJapan

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