PharmacoEconomics

, Volume 20, Issue 2, pp 119–137 | Cite as

Tamoxifen Plus Chemotherapy versus Tamoxifen Alone as Adjuvant Therapies for Node-Positive Postmenopausal Women with Early Breast Cancer

A Stochastic Economic Evaluation
Original Research Article

Abstract

Background: There remains uncertainty around the appropriate choice of adjuvant therapies to offer postmenopausal women with node-positive early breast cancer.

Objective and study design: To present the results derived from a discrete event simulation (DES)model that compared tamoxifen plus chemotherapy versus tamoxifen alone in node-positive postmenopausal women diagnosed with early breast cancer.

Methods: The data populating the model were mainly derived from the existing literature, which was analysed to specify probability distributions describing the uncertainty around the true value of each input parameter. The specified probability distributions facilitated the stochastic analysis of the decision model, whereby distributions of the model’s outputs [aggregate costs and quality-adjusted life years (QALYs)] were estimated.

Results: The baseline results show that the addition of chemotherapy to tamoxifen in this patient group is relatively cost effective (under £4000 per additional QALY), but the distribution of the incremental cost-effectiveness ratio shows a wide range, including 10% of observations in which tamoxifen dominates tamoxifen plus chemotherapy.

Conclusions: The results demonstrate the intuitive nature of stochastic evaluations of healthcare technologies, which may ease decision-makers’ interpretation of cost-effectiveness results.

References

  1. 1.
    Cancer Research Campaign. Fact sheet 1: Incidence. London: CRC Publications, 1998Google Scholar
  2. 2.
    Fowble B. Staging of breast cancer. In: Fowble B, Goodman RL, Glick JH, et al., editors. Breast cancer treatment: a comprehensive guide to management. St Louis (MO): Mosby Year Book, 1991Google Scholar
  3. 3.
    Glick JH. Adjuvant therapy for node-negative breast cancer. In: Fowble B, Goodman RL, Glick JH, et al., editors. Breast cancer treatment: a comprehensive guide to management, St Louis (MO): Mosby Year Book, 1991Google Scholar
  4. 4.
    Early Breast Cancer Trialists Collaborative Group. Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women. Lancet 1992; 339: 71–85Google Scholar
  5. 5.
    Early Breast Cancer Trialists Collaborative Group. Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet 1998; 352 (9132): 930–42CrossRefGoogle Scholar
  6. 6.
    de Haes JC, de Koning HJ, van Oortmarssen GJ, et al. The impact of a breast cancer screening programme on quality-adjusted life-years. Int J Cancer 1991; 49 (4): 538–44PubMedCrossRefGoogle Scholar
  7. 7.
    Hillier FS, Lieberman GJ. Introduction to operations research. New York (NY): McGraw-Hill, 1995Google Scholar
  8. 8.
    Felli JC, Hazen GB. Sensitivity analysis and the expected value of perfect information. Med Decis Making 1998; 18 (1): 95–109PubMedCrossRefGoogle Scholar
  9. 9.
    Lober J, Sogaard J, Mouridsen HT, et al. Treatment costs of adjuvant cytotoxic therapy in premenopausal breast cancer patients. Acta Oncol 1988; 27 (6A): 767–71PubMedCrossRefGoogle Scholar
  10. 10.
    Pasta DJ, Taylor JL, Henning JM. Probabilistic sensitivity analysis incorporating the bootstrap: an example comparing treatments for the eradication of Helicobacter pylori. Med Decis Making 1999; 19 (3): 353–63PubMedCrossRefGoogle Scholar
  11. 11.
    Briggs AH. A bayesian approach to stochastic cost-effectiveness analysis. Health Econ 1999; 8 (3): 257–61PubMedCrossRefGoogle Scholar
  12. 12.
    Iverson GR. Bayesian statistical inference: Sage, 1984Google Scholar
  13. 13.
    Rice JA. Mathematical statistics and data analysis. Belmont (CA): Duxberry Press, 1995Google Scholar
  14. 14.
    Fairclough DL. Summary measures and statistics for comparison of quality of life in a clinical trial of cancer therapy. Stat Med 1997; 16 (11): 1197–209PubMedCrossRefGoogle Scholar
  15. 15.
    Fisher B, Dignam J, Wolmark N, et al. Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer [see comments]. J Natl Cancer Inst 1997; 89 (22): 1673–82PubMedCrossRefGoogle Scholar
  16. 16.
    Pritchard KI, Paterson AH, Paul NA, et al. Increased thromboembolic complications with concurrent tamoxifen and chemotherapy in a randomized trial of adjuvant therapy for women with breast cancer. National Cancer Institute of Canada Clinical Trials Group. Breast Cancer Site Group. J Clin Oncol 1996; 14 (10): 2731–7PubMedGoogle Scholar
  17. 17.
    Rivkin SE, Green S, Metch B, et al. Adjuvant CMFVP versus tamoxifen versus concurrent CMFVP and tamoxifen for postmenopausal, node-positive, and estrogen receptor-positive breast cancer patients: a Southwest Oncology Group study [see comments]. J Clin Oncol 1994; 12 (10): 2078–85Google Scholar
  18. 18.
    Toonkel LM, Ivor F, Jacobson LH, et al. The significance of local recurrence of carcinoma of the breast. Int J Radiat Oncol Biol Phys 1983; 9: 33–9PubMedCrossRefGoogle Scholar
  19. 19.
    Bergman L, van Dongen JA, van Ooijen B, et al. Should tamoxifen be a primary treatment choice for elderly breast cancer patients with locoregional disease? Breast Cancer Res Treat 1995; 34 (1): 77–83PubMedCrossRefGoogle Scholar
  20. 20.
    Fenwick E, Claxton K, Sculpher M, et al. Improving the efficiency and relevance of health technology assessment: the role of iterative decision analytic modelling. CHE discussion paper. York: University of York, 2000Google Scholar
  21. 21.
    Pritchard KI, Paterson AH, Fine S, et al. Randomized trial of cyclophosphamide, methotrexate, and fluorouracil chemotherapy added to tamoxifen as adjuvant therapy in postmenopausal women with node-positive estrogen and/or progesterone receptor-positive breast cancer: a report of the National Cancer Institute of Canada Clinical Trials Group. Breast Cancer Site Group. J Clin Oncol 1997; 15 (6): 302–11Google Scholar
  22. 22.
    Holloway RG, Witter Jr DM, Lawton KB, et al. Inpatient costs of specific cerebrovascular events at five academic medical centers [see comments]. Neurology 1996; 46 (3): 854–60PubMedGoogle Scholar
  23. 23.
    Lloyd A, Aitken JA, Hoffmeyer UKO, et al. Economic evaluation of the use of nadroparin calcium in the prophylaxis of deep vein thrombosis and pulmonary embolism in surgical patients in Italy. Pharmacoeconomics 1997; 12 (4): 475–85PubMedCrossRefGoogle Scholar
  24. 24.
    Leese B. The costs of treating febrile neutropenia in six UK hospitals. Eur J Cancer 1993; 29A Suppl. 7: S15-8PubMedCrossRefGoogle Scholar
  25. 25.
    Coombes RC, Bliss JM, Wils J, et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. The international collaborative cancer group. J Clin Oncol 1996; 14 (1): 35–45PubMedGoogle Scholar
  26. 26.
    Schumacher M, Bastert G, Bojar H, et al. Randomized 2 × 2 trial evaluating hormonal treatment and the duration of chemotherapy in node-positive breast cancer patients. German Breast Cancer Study Group. J Clin Oncol 1994; 12 (10): 2086–93PubMedGoogle Scholar
  27. 27.
    Castiglione-Gertsch M, Johnsen C, Goldhirsch A, et al. The international (Ludwig) breast cancer study group trials i–iv: 15 years follow-up. Ann Oncol 1994; 5 (8): 717–24PubMedGoogle Scholar
  28. 28.
    Gerard JP, Hery M, Gedouin D, et al. Postmenopausal patients with node-positive resectable breast cancer. Tamoxifen vs FEC 50 (6 cycles) vs FEC 50 (6 cycles) plus tamoxifen vs control - preliminary results of a 4-arm randomised trial. The French Adjuvant Study Group. Drugs 1993; 45 Suppl.: 60–7PubMedCrossRefGoogle Scholar
  29. 29.
    Gelber RD, Cole BF, Goldhirsch A. How to compare quality of life of breast cancer patients in clinical trials. International Breast Cancer Study Group [review]. Recent Results Cancer Res 1993; 127: 221–33PubMedCrossRefGoogle Scholar
  30. 30.
    Jardines L, Callans LS, Torosian MH. Recurrent breast cancer: presentation, diagnosis, and treatment [review]. Semin Oncol 1993; 20 (5): 538–47PubMedGoogle Scholar
  31. 31.
    Willner J, Kiricuta IC, Kolbl O. Locoregional recurrence of breast cancer following mastectomy: always a fatal event? Results of univariate and multivariate analysis. Int J Radiat Oncol Biol Phys 1997; 37 (4): 853–63PubMedCrossRefGoogle Scholar
  32. 32.
    Beck TM, Hart NE, Woodard DA, et al. Local or regionally recurrent carcinoma of the breast: results of therapy in 121 patients. J Clin Oncol 1983; 1 (6): 400–5PubMedGoogle Scholar
  33. 33.
    Bedwinek JM, Fineberg B, Lee J, et al. Analysis of failures following local treatment of isolated local- regional recurrence of breast cancer. Int J Radiat Oncol Biol Phys 1981; 7 (5): 581–5PubMedCrossRefGoogle Scholar
  34. 34.
    Borner MM, Bacchi M, Castiglione M. Possible deleterious effect of tamoxifen in premenopausal women with locoregional recurrence of breast cancer. Eur J Cancer 1996; 32A (12): 2173–6PubMedCrossRefGoogle Scholar
  35. 35.
    Crowe Jr JP, Gordon NH, Antunez AR, et al. Local-regional breast cancer recurrence following mastectomy. Arch Surg 1991; 126 (4): 429–32PubMedCrossRefGoogle Scholar
  36. 36.
    Janjan NA, McNeese MD, Buzdar AU, et al. Management of locoregional recurrent breast cancer. Cancer 1986; 58: 1552–6PubMedCrossRefGoogle Scholar
  37. 37.
    Schwaibold F, Fowble BL, Solin LJ, et al. The results of radiation therapy for isolated local regional recurrence after mastectomy. Int J Radiat Oncol Biol Phys 1991; 21: 299–310PubMedCrossRefGoogle Scholar
  38. 38.
    Alonso MC, Tabernero JM, Ojeda B, et al. Aphase III randomized trial of cyclophosphamide, mitoxantrone, and 5-fluorouracil (cnf) versus cyclophosphamide, adriamycin, and 5-fluorouracil (caf) in patients with metastatic breast cancer. Breast Cancer Res Treat 1995; 34 (1): 15–24PubMedCrossRefGoogle Scholar
  39. 39.
    Arai Y, Sone Y, Inaba Y, et al. Hepatic arterial infusion chemotherapy for livermetastases frombreast cancer. CancerChemother Pharmacol 1994; 33 Suppl.: S142–4CrossRefGoogle Scholar
  40. 40.
    Castiglione-Gertsch M, Tattersall M, Hacking A, et al. Retreating recurrent breast cancer with the same CMF-containing regimen used as adjuvant therapy. The International Breast Cancer Study Group. Eur J Cancer 1997; 33 (14): 2321–5PubMedCrossRefGoogle Scholar
  41. 41.
    Clark GM, Sledge Jr GW, Osborne CK, et al. Survival from first recurrence: relative importance of prognostic factors in 1015 breast cancer patients. J Clin Oncol 1987; 5 (1): 55–61PubMedGoogle Scholar
  42. 42.
    Coleman RE, Rubens RD. The clinical course of bone metastases from breast cancer. Br J Cancer 1987; 55 (1): 61–6PubMedCrossRefGoogle Scholar
  43. 43.
    Goldhirsch A, Gelber RD, Castiglione M. Relapse of breast cancer after adjuvant treatment in premenopausal and perimenopausal women: patterns and prognoses. J Clin Oncol 1988; 6 (1): 89–97PubMedGoogle Scholar
  44. 44.
    Kamby C, Ejlertsen B, Andersen J, et al. The pattern of metastases in human breast cancer: influence of systemic adjuvant therapy and impact on survival. Acta Oncol 1988; 27 (6A): 715–9PubMedCrossRefGoogle Scholar
  45. 45.
    Koenders PG, Beex LV, Kloppenborg PW, et al. Human breast cancer: survival from first metastasis. Breast Cancer Study Group. Breast Cancer Res Treat 1992; 21 (3): 173–80CrossRefGoogle Scholar
  46. 46.
    Leonard RC, Rodger A, Dixon JM. ABC of breast diseases: metastatic breast cancer [review]. BMJ 1994; 309 (6967): 1501–4PubMedCrossRefGoogle Scholar
  47. 47.
    Macquart-Moulin G, Viens P, Genre D, et al. Concomitant chemoradiotherapy for patients with nonmetastatic breast carcinoma: side effects, quality of life, and organization. Cancer 1999; 85 (10): 2190–9PubMedCrossRefGoogle Scholar
  48. 48.
    Rasmusson B, Vejborg I, Jensen AB, et al. Irradiation of bone metastases in breast cancer patients: a randomized study with 1 year follow-up. Radiother Oncol 1995; 34 (3): 179–84PubMedCrossRefGoogle Scholar
  49. 49.
    Tormey DC, Gray R, Abeloff MD, et al. Adjuvant therapy with a doxorubicin regimen and long-term tamoxifen in premenopausal breast cancer patients: an Eastern Cooperative Oncology Group Trial. J Clin Oncol 1992; 10 (12): 1848-56PubMedGoogle Scholar
  50. 50.
    Rubens RD. Key issues in the treatment of advanced breast cancer: expectations and outcomes. Pharmacoeconomics 1996; 9 Suppl. 2: 1–7PubMedCrossRefGoogle Scholar
  51. 51.
    Wong K, Henderson IC. Management of metastatic breast cancer [review]. World J Surg 1994; 18 (1): 98–111PubMedCrossRefGoogle Scholar
  52. 52.
    Hurley SF, Huggins RM, Snyder RD, et al. The cost of breast cancer recurrences. Br J Cancer 1992; 65: 449–55PubMedCrossRefGoogle Scholar
  53. 53.
    Bernhard J, Hurny C, Coates AS, et al. Quality of life assessment in patients receiving adjuvant therapy for breast cancer: the IBCSG approach. The International Breast Cancer Study Group. Ann Oncol 1997; 8 (9): 825–35PubMedCrossRefGoogle Scholar
  54. 54.
    Hurny C, Bernhard J, Coates AS, et al. Impact of adjuvant therapy on quality of life in women with node-positive operable breast cancer. International Breast Cancer Study Group [published erratum appears in Lancet 1997 Jul 26; 350 (9073): 298]. Lancet 1996; 347 (9011): 1279–84PubMedGoogle Scholar
  55. 55.
    Lord J, Asante MA. Estimating uncertainty ranges for costs by the bootstrap procedure combined with probabilistic sensitivity analysis. Health Econ 1999; 8 (4): 323–33PubMedCrossRefGoogle Scholar
  56. 56.
    Ashby J, O’Hanlon M, Buxton MJ. The time trade-off technique: how do the valuations of breast cancer patients compare to those of other groups? Qual Life Res 1994; 3 (4): 257–65PubMedCrossRefGoogle Scholar
  57. 57.
    Bratley P, Fox BL, Schrage LE. A guide to simulation. New York (NY): Springer-Verlag, 1987CrossRefGoogle Scholar
  58. 58.
    Halpern MT, Luce BR, Brown RE, et al. Health and economic outcomes modeling practices: a suggested framework. Value Health 1998; 1 (2): 131–47PubMedCrossRefGoogle Scholar
  59. 59.
    Sculpher M, Fenwick E, Claxton K. Assessing quality in decision analytic cost-effectiveness models: a suggested framework and example of application. Pharmacoeconomics 2000; 17 (5): 461–77PubMedCrossRefGoogle Scholar
  60. 60.
    Hillner BE, Smith TJ. Estimating the efficacy and cost-effectiveness of tamoxifen versus tamoxifen plus adjuvant chemotherapy in post-menopausal node positive breast cancer: a decision analysis model [abstract]. Proc Am Soc Clin Oncol 1992; 11: 55Google Scholar
  61. 61.
    Will BP, Berthelot JM, Houle C, et al. The economic impact of locoregional radiotherapy (LRRT) on all post-surgical stage 2 breast cancer patients in Canada. Statistics Canada/ Ottawa Regional Cancer Centre. Statistics Canada, Ottawa (ON), CanadaGoogle Scholar
  62. 62.
    Wolstenholme J, Whynes D. The costs of treating breast cancer: implications for screening. Int J Technol Assess Health Care 1998 14; (2): 277–89PubMedCrossRefGoogle Scholar
  63. 63.
    Cummings FJ, Gray R, Tormey DC, et al. Adjuvant tamoxifen versus placebo in elderly women with node-positive breast cancer: long-term follow-up and causes of death [see comments]. J Clin Oncol 1993; 11 (1): 29–35PubMedGoogle Scholar
  64. 64.
    Briggs AH. Handling uncertainty in cost-effectiveness models. Pharmacoeconomics 2000; 17 (5): 479–500PubMedCrossRefGoogle Scholar
  65. 65.
    Her Majesty’s Treasury. Appraisal and evaluation in central government. London: Her Majesty’s Stationery Office, 1997Google Scholar
  66. 66.
    CIPFA. The Health Service Database. 1999Google Scholar
  67. 67.
    British National Formulary. London, United Kingdom: British Medical Association, Royal Pharmaceutical Society of Great Britain, 2000 MarchGoogle Scholar
  68. 68.
    Lokich JJ, Moore CL, Anderson NR. Comparison of costs for infusion versus bolus chemotherapy administration: analysis of five standard chemotherapy regimens in three common tumors. Part one:model projections for cost based on charges. Cancer 1996 Jul 15; 78 (2): 294–9Google Scholar
  69. 69.
    Reference Costs 2000. London, United Kingdom: Department of Health, 2000Google Scholar
  70. 70.
    East Anglia Hospital Trust. East Anglia costs 1999. East Anglia, United Kingdom: East Anglia Hospital Trust, 1999Google Scholar
  71. 71.
    Silva OE, Zurrida S. Breast cancer: a guide for fellows. Amsterdam: Elsevier; 1999Google Scholar
  72. 72.
    Wakker P, Klaassen M. Confidence intervals for cost-effectiveness ratios. Health Econ 1995; 4 (5): 373–81PubMedCrossRefGoogle Scholar
  73. 73.
    Briggs A, Fenn P. Confidence intervals or surfaces?Uncertainty on the cost-effectiveness plane. Health Econ 1998; 7 (8): 723–40PubMedCrossRefGoogle Scholar
  74. 74.
    Earle CC, Chapman RH, Baker CS, et al. Systematic overview of cost-utility assessments in oncology. J Clin Oncol 2000 Sep 15; 18 (18): 3302–17Google Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  1. 1.Health Economics Research GroupBrunel UniversityUxbridge, MiddlesexUK

Personalised recommendations