Abstract
Adjuvant tamoxifen therapy for 5 years reduces recurrence in hormone receptor positive, post-menopausal women with early breast cancer, but offers no advantage when prolonged to another 5 years, during which the risk of recurrence remains high. Treating patients, who remain disease-free after 5 years of tamoxifen, with letrozole significantly reduces recurrence, regardless of nodal status. This study evaluated the life-time cost-utility of extended adjuvant letrozole therapy in 62-year-old patients from a third-party payer perspective. A Markov model incorporated locoregional, contralateral, and metastatic recurrences. The comparator was placebo. Event rates were based on published trials. Utility values were taken from a clinical trial and published literature. Costs were obtained from published literature, provincial payment schedules, cancer agencies, and drug plans formularies. Resource use reflected Canadian treatment patterns. Robustness of the model was tested using deterministic and probabilistic sensitivity analyses. Extended adjuvant letrozole therapy of a cohort consisting of 50% node-negative and 50% node-positive patients prolonged their lives on average by 0.466 years or 0.267 quality-adjusted life years (QALYs) at an additional cost of Can$8,031 per patient, yielding an incremental cost-utility ratio (ICUR) of $34,058 per QALY. Letrozole was more cost-effective in node-positive than in node-negative patients (Can$26,553 vs Can$46,049 per QALY). Results were robust to variations in age, healthcare costs, and utilities. The degree of confidence that the cost per QALY would be below Can$50,000 reached 100% for node-positive and 77% for node-negative patients. Extended adjuvant letrozole is cost-effective in both node-negative and node-positive patients having ICURs below Can$50,000/QALY.
Similar content being viewed by others
References
Shibuya K, Mathers CD, Boschi-Pinto C, Lopez AD, Murray␣CJ (2002) Global and regional estimates of cancer mortality and incidence by site: II. Results for the global burden of disease 2000. BMC Cancer 2:37
Bray F, McCarron P, Parkin DM (2004) The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res 6(6):229–239
Hewitt M, Breen N, Devesa S (1999) Cancer prevalence and survivorship issues: analyses of the 1992 National Health Interview Survey. J Natl Cancer Inst 91(17):1480–1486
Harris JR, Morrow M, Bonadonna G (1993) Cancer of the breast. In: DeVita VT, Hellman S, Rosenberg SA (eds) Cancer: principles and practice of oncology, 4th edn. J.B. Lippincott Co., Philadelphia, pp 1264–1332
Glick J (1991) Adjuvant therapy for node-negative breast cancer. In: Fowble B, Goodman R, Glick JH, Rosato E (eds) Breast cancer treatment. A comprehensive guide to management. Mosby Year Book, St Louis
Early Breast Cancer Trialists’ Collaborative Group (1998) Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351(9114):1451–1467
Fisher B, Dignam J, Bryant J, Wolmark N (2001) Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. J␣Natl Cancer Inst 93(9):684–690
Fisher B, Dignam J, Bryant J, DeCillis A, Wickerham DL, Wolmark N, Costantino J, Redmond C, Fisher ER, Bowman DM, Deschenes L, Dimitrov NV, Margolese RG, Robidoux A, Shibata H, Terz J, Paterson AH, Feldman MI, Farrar W, Evans J, Lickley HL (1996) Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst 88(21):1529–1542
Kaufmann M, Rody A (2005) Long-term risk of breast cancer recurrence: the need for extended adjuvant therapy. J␣Cancer Res Clin Oncol 131(8):487–494
Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ, Pater JL (2003) A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J␣Med 349(19):1793–1802
Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Cameron DA, Palmer MJ, Pater JL (2005) Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst 97(17):1262–1271
Radice D, Redaelli A (2003) Breast cancer management: quality-of-life and cost considerations. Pharmacoeconomics 21(6):383–396
Canadian Coordinating Office for Health Technology Assessment. Guidelines for economic evaluation of pharmaceuticals: Canada. CCOHTA 1997 November (Nov 1997) Available from: URL: http://www.ccohta.ca
Karnon J, Jones T (2003) A stochastic economic evaluation of letrozole versus tamoxifen as a first-line hormonal therapy: for advanced breast cancer in postmenopausal patients. Pharmacoeconomics 21(7):513–525
Borner M, Bacchi M, Goldhirsch A, Greiner R, Harder F, Castiglione M, Jungi WF, Thurlimann B, Cavalli F, Obrecht JP (1994) Swiss Group for Clinical Cancer Research: first isolated locoregional recurrence following mastectomy for breast cancer: results of a phase III multicenter study comparing systemic treatment with observation after excision and radiation. J Clin Oncol 12(10):2071–2077
Doyle T, Schultz DJ, Peters C, Harris E, Solin LJ (2001) Long-term results of local recurrence after breast conservation treatment for invasive breast cancer. Int J Radiat Oncol Biol Phys 51(1):74–80
Haylock BJ, Coppin CM, Jackson J, Basco VE, Wilson KS (2000) Locoregional first recurrence after mastectomy: prospective cohort studies with and without immediate chemotherapy. Int J Radiat Oncol Biol Phys 46(2):355–362
Janjan NA, McNeese MD, Buzdar AU, Montague ED, Oswald MJ (1986) Management of locoregional recurrent breast cancer. Cancer 58(7):1552–1556
Kamby C, Sengelov L (1997) Pattern of dissemination and survival following isolated locoregional recurrence of breast cancer: a prospective study with more than 10 years of follow up. Breast Cancer Res Treat 45(2):181–192
Koning C, Hart G (1998) Long-term follow-up of a randomized trial on adjuvant chemotherapy and hormonal therapy in locally advanced breast cancer. Int J Radiat Oncol Biol Phys 41(2):397–400
Moran MS, Haffty BG (2002) Local-regional breast cancer recurrence: prognostic groups based on patterns of failure. Breast J 8(2):81–87
Schmoor C, Sauerbrei W, Bastert G, Schumacher M (2000) Role of isolated locoregional recurrence of breast cancer: results of four prospective studies. J Clin Oncol 18(8):1696–1708
Schwaibold F, Fowble BL, Solin LJ, Schultz DJ, Goodman RL (1991) The results of radiation therapy for isolated local regional recurrence after mastectomy. Int J Radiat Oncol Biol Phys 21(2):299–310
Toi M, Tanaka S, Bando M, Hayashi K, Tominaga T (1997) Outcome of surgical resection for chest wall recurrence in breast cancer patients. J Surg Oncol 64(1):23–26
Toonkel LM, Fix I, Jacobson LH, Wallach CB (1983) The significance of local recurrence of carcinoma of the breast. Int J Radiat Oncol Biol Phys 9(1):33–39
Jassem J, Pienkowski T, Pluzanska A, Jelic S, Gorbunova V, Mrsic-Krmpotic Z, Berzins J, Nagykalnai T, Wigler N, Renard J, Munier S, Weil C (2001) Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer: final results of a randomized phase III multicenter trial. J␣Clin Oncol 19(6):1707–1715
Mouridsen H, Gershanovich M, Sun Y, Perez-Carrion R, Boni C, Monnier A, Apffelstaedt J, Smith R, Sleeboom HP, Janicke F, Pluzanska A, Dank M, Becquart D, Bapsy PP, Salminen E, Snyder R, Lassus M, Verbeek JA, Staffler B, Chaudri-Ross HA, Dugan M (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(10):2596–2606
Statistics Canada. Statistics Canada 2005 Available from: URL: http://www.statisticscanada.com/
Wai ES, Trevisan CH, Taylor SCM, Mates D, Jackson JS, Olivotto IA (2001) Health system costs of metastatic breast cancer. Breast Cancer Res Treat 65(3):233–240
Canadian Institute for Health Information (2001) Resource Intensity Weights and Expected Length of Stay
Will BP, Berthelot JM, Le Petit C, Tomiak EM, Verma S, Evans WK (2000) Estimates of the lifetime costs of breast cancer treatment in Canada. Eur J Cancer 36(6):724–735
Cancer Care Ontario (2004) Cancer Care Ontario formulary regimen
Ministry of Health Services Government of British Columbia (2004) Pharmacare Canadian Drug Identity Code
Earle C, Coyle D, Smith A, Agboola O, Evans WK (1999) The cost of radiotherapy at an Ontario regional cancer centre: a re-evaluation. Crit Rev Oncol Hematol 32(2):87–93
Alberta Health & Wellness Government of Alberta (2004) Health Care Insurance Plan & Services
Alberta Learning Information Service. Alberta wage and salary survey. Alberta Human resource and employment 2003 [cited 2003]; Available from: URL: http://www.alis.gov.ab.ca/wageinfo/Content/RequestAction.asp?aspAction=GetWageDetail&format=html&RegionID=20&NOC=3131
Ministry of Health Services Government of British Columbia (2003) British Columbia Medical Services Plan
Ministry of health and long term care Ontario (2003) Ontario Health Insurance Plan
Thomson Healthcare I. Redbook (2003) Pharmacy’s Fundamental Reference. Thomson, Montvale, New Jersey
Statistics Canada (2002) Consumer Price Index for Health Care, Table 326-0002, Series v737544. Ottawa
de Haes JC, de Koning HJ, van Oortmarssen GJ, van Agt␣HM, de Bruyn AE, Der Maas PJ (1991) The impact of a breast cancer screening programme on quality-adjusted life-years. Int J Cancer 49(4):538–544
Briggs AH (2000) Handling uncertainty in cost-effectiveness models. Pharmacoeconomics 17(5):479–500
Briggs AH, O’Brien BJ, Blackhouse G (2002) Thinking outside the box: recent advances in the analysis and presentation of uncertainty in cost-effectiveness studies. Annu Rev Public Health 23:377–401
Critchfield GC, Willard KE (1986) Probabilistic analysis of decision trees using Monte Carlo simulation. Med Decis Making 6(2):85–92
Doubilet P, Begg CB, Weinstein MC, Braun P, McNeil BJ (1985) Probabilistic sensitivity analysis using Monte Carlo simulation. A practical approach. Med Decis Making 5(2):157–177
Karnon J, Delea T, Johnston SR, Smith R, Brandman J, Sung J, Goss PE (2006) Cost effectiveness of extended adjuvant letrozole in postmenopausal women after adjuvant tamoxifen therapy: the UK perspective. Pharmacoeconomics 24(3):237–250
Marchetti M, Caruggi M, Colombo G (2004) Cost utility and budget impact of third-generation aromatase inhibitors for advanced breast cancer: a literature-based model analysis of costs in the Italian National Health Service. Clin Ther 26(9):1546–1561
Karnon J, Johnston SR, Jones T, Glendenning A (2003) A trial-based cost-effectiveness analysis of letrozole followed by tamoxifen versus tamoxifen followed by letrozole for postmenopausal advanced breast cancer. Ann Oncol 14(11):1629–1633
Dranitsaris G, Verma S, Trudeau M (2003) Cost utility analysis of first-line hormonal therapy in advanced breast cancer: comparison of two aromatase inhibitors to tamoxifen. Am J Clin Oncol 26(3):289–296
Nuijten M, Meester L, Waibel F, Wait S (1999) Cost effectiveness of letrozole in the treatment of advanced breast cancer in postmenopausal women in the UK. Pharmacoeconomics 16(4):379–397
Dranitsaris G, Leung P, Mather J, Oza A (2000) Cost-utility analysis of second-line hormonal therapy in advanced breast cancer: a comparison of two aromatase inhibitors to megestrol acetate. Anticancer Drugs 11(7):591–601
Benedict A, Brown RE (2005) Review of cost-effectiveness analyses in hormonal therapies in advanced breast cancer. Expert Opin Pharmacother 6(11):1789–1801
Gail MH, Costantino JP, Bryant J, Croyle R, Freedman L, Helzlsouer K, Vogel V (1999) Weighing the risks and benefits of tamoxifen treatment for preventing breast cancer. J␣Natl Cancer Inst 91(21):1829–1846
Hershman D, Sundararajan V, Jacobson JS, Heitjan DF, Neugut AI, Grann VR (2002) Outcomes of tamoxifen chemoprevention for breast cancer in very high-risk women: a cost-effectiveness analysis. J Clin Oncol 20(1):9–16
Cykert S, Phifer N, Hansen C (2004) Tamoxifen for breast cancer prevention: a framework for clinical decisions. Obstet Gynecol 104(3):433–442
Eckermann SD, Martin AJ, Stockler MR, Simes RJ (2003) The benefits and costs of tamoxifen for breast cancer prevention. Aust NZ J Public Health 27(1):34–40
Ravdin PM, Davis GJ (2004) A method for making estimates of the benefit of the late use of letrozole in patients completing 5 years of tamoxifen. Clin Breast Cancer 5(4):313–316
Eichler HG, Kong SX, Gerth WC, Mavros P, Jonsson B (2004) Use of cost-effectiveness analysis in health-care resource allocation decision-making: how are cost-effectiveness thresholds expected to emerge? Value Health 7(5):518–528
Perez DJ, Williams SM, Christensen EA, McGee RO, Campbell AV (2001) A longitudinal study of health related quality of life and utility measures in patients with advanced breast cancer. Qual Life Res 10(7):587–593
Ganz PA, Desmond KA, Leedham B, Rowland JH, Meyerowitz BE, Belin TR (2002) Quality of life in long-term, disease-free survivors of breast cancer: a follow-up study. J␣Natl Cancer Inst 94(1):39–49
Fallowfield L, McGurk R, Dixon M (2004) Same gain, less pain: potential patient preferences for adjuvant treatment in premenopausal women with early breast cancer. Eur J Cancer 40(16):2403–2410
Goodwin PJ, Black JT, Bordeleau LJ, Ganz PA (2003) Health-related quality-of-life measurement in randomized clinical trials in breast cancer – taking stock. J Natl Cancer Inst 95(4):263–281
Whelan TJ, Goss PE, Ingle JN, Pater JL, Tu D, Pritchard K, Liu S, Shepherd LE, Palmer M, Robert NJ, Martino S, Muss␣HB (2005) Assessment of Quality of Life in MA.17: a randomized, placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women. J Clin Oncol 23(28):6931–6940
Acknowledgements
Funding for this study came from Novartis Pharma. This article was prepared with the assistance of BioMedCom Consultants inc, Montreal, Canada.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ouagari, K.E., Karnon, J., Delea, T. et al. Cost-Effectiveness of Letrozole in the Extended Adjuvant Treatment of Women with Early Breast Cancer. Breast Cancer Res Treat 101, 37–49 (2007). https://doi.org/10.1007/s10549-006-9262-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-006-9262-4