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Cost-utility of the 21-gene recurrence score assay in node-negative and node-positive breast cancer

  • Epidemiology
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Abstract

The 21-gene recurrence score (Oncotype DX®: RS) appears to augment clinico-pathologic prognostication and is predictive of adjuvant chemotherapy benefit in node-negative (N−) and node-positive (N+), endocrine-sensitive breast cancer. RS is a costly assay that is associated with good ‘value for money’ in N− disease, while economic evaluations in N+ disease based on most recent data have not been conducted. We examined the cost-utility (CU) of a RS-guided adjuvant strategy, compared to current practice without RS in N− and N+, endocrine-sensitive, breast cancer from a Canadian health care system perspective. A generic state-transition model was developed to compute cumulative costs and quality-adjusted life years (QALYs) over a 25-year horizon. Patient outcomes with and without chemotherapy in RS-untested cohorts and in those with low, intermediate and high RS were examined based on the reported prognostic and predictive impact of RS in N− and N+ disease. Chemotherapy utilization (current vs. RS-guided), unit costs and utilities were derived from a Nova Scotia Canadian population-based cohort, local unit costs and the literature. Costs and outcomes were discounted at 3% annually, and costs were reported in 2011 Canadian dollars ($). Probabilistic and one-way sensitivity analyses were conducted for key model parameters. Compared to a non-RS-guided strategy, RS-guided adjuvant therapy was associated with $2,585 and $864 incremental costs, 0.27 and 0.06 QALY gains, and resultant CUs of $9,591 and $14,844 per QALY gained for N− and N+ disease, respectively. CU estimates were robust to key model parameters, and were most sensitive to chemo utilization proportions. RS-guided adjuvant therapy appears to be a cost-effective strategy in both N− and N+, endocrine-sensitive breast cancer with resultant CU ratios well below commonly quoted thresholds.

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References

  1. Burstein HJ, Prestrud AA, Seidenfeld J et al (2010) American society of clinical oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol 28:3784–3796

    Article  PubMed  Google Scholar 

  2. Goldhirsch A, Wood WC, Coates AS et al (2011) Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22:1736–1747

    Article  PubMed  CAS  Google Scholar 

  3. Carlson RW, Allred DC, Anderson BO et al (2009) Breast cancer—clinical practice guidelines in oncology. J Natl Compr Cancer Netw 7:122–192

    CAS  Google Scholar 

  4. Barron JJ, Quimbo R, Nikam PT, Amonkar MM (2008) Assessing the economic burden of breast cancer in a US managed care population. Breast Cancer Res Treat 109:367–377

    Article  PubMed  Google Scholar 

  5. Broekx S, Den Kond E, Torfs R et al (2011) The costs of breast cancer prior to and following diagnosis. Eur J Health Econ 12:311–317

    Article  PubMed  Google Scholar 

  6. Dowsett M, Goldhirsch A, Hayes DF, Senn HJ, Wood W, Viale G (2007) International web-based consultation on priorities for translational breast cancer research. Breast Cancer Res 9:R81

    Article  PubMed  Google Scholar 

  7. Harris L, Fritsche H, Mennel R et al (2007) American society of clinical oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 25:5287–5312

    Article  PubMed  CAS  Google Scholar 

  8. Paik S, Shak S, Tang G et al (2004) A multigene assay to predict the recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351:2817–2826

    Article  PubMed  CAS  Google Scholar 

  9. Paik S, Tang G, Shak S et al (2006) Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 24:3726–3734

    Article  PubMed  CAS  Google Scholar 

  10. Albain KS, Barlow WE, Shak S et al (2010) Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol 11:55–65

    Article  PubMed  CAS  Google Scholar 

  11. Lo SS, Mumby P, Norton J et al (2010) Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection. J Clin Oncol 28:1671–1676

    Article  PubMed  Google Scholar 

  12. Oratz R, Paul D, Cohn AL, Sedlacek SL (2007) Impact of a commercial reference laboratory test recurrence score on decision making in early-stage breast cancer. J Oncol Pract 3:182–187

    Article  PubMed  Google Scholar 

  13. Hornberger J, Cosler LE, Lyman GH (2005) Economic analysis of targeting chemotherapy using a 21- gene RT-PCR assay in Lymph-node-negative, estrogen-receptor-positive, early-stage breast cancer. Am J Manag Care 11:313–324

    PubMed  Google Scholar 

  14. Lyman GH, Cosler LE, Kuderer NM, Hornberger J (2007) Impact of a 21-gene RT-PCR Assay on treatment decisions in early-stage breast cancer: an economic analysis based on prognostic and predictive validation studies. Cancer 109:1011–1018

    Article  PubMed  Google Scholar 

  15. Kondo M, Hoshi SL, Ishiguro H, Yoshibayashi H, Toi M (2008) Economic evaluation of 21-gene reverse transcriptase-polymerase chain reaction assay in lymph-node-negative, estrogen-receptor-positive, early-stage breast cancer in Japan. Breast Cancer Res Treat 112(1):175–187

    Article  PubMed  Google Scholar 

  16. Cosler LE, Lyman GH (2009) Economic analysis of gene expression profile data to guide adjuvant treatment in women with early-stage breast cancer. Cancer Investig 27:953–959

    Article  Google Scholar 

  17. Tsoi DT, Inoue M, Kelly CM, Verma S, Pritchard KI (2010) Cost-effectiveness analysis of recurrence score-guided treatment using a 21-gene assay in early breast cancer. The Oncologist 15:457–465

    Article  PubMed  Google Scholar 

  18. Klang SH, Hammerman A, Liebermann N, Efrat N, Doberne J, Hornberger J (2010) Economic implications of 21-gene breast cancer risk assay from the perspective of an israeli-managed health-care organization. Value Health 13:381–387

    Article  PubMed  Google Scholar 

  19. Kondo M, Hoshi S, Yamanaka T, Ishiguro H, Toi M (2011) Economic evaluation of the 21-gene signature (Oncotype DX) in lymph node-negative/positive, hormone receptor-positive early-stage breast cancer based on Japanese validation study (JBCRG-TR03). Breast Cancer Res Treat 127:739–749

    Article  PubMed  Google Scholar 

  20. Snow S, Rayson D, Barnes PJ, Sellon M, Thompson K, Younis T. (2008) Does Her2/neu status affect adjuvant chemotherapy utilization? A population based analysis. Poster Presentation at the American Society of Clinical Oncology Breast Cancer Symposium: Washington, DC. Sept 2008

  21. Ademuyiwa FO, Miller A, Edge SB et al (2011) The effects of oncotype DX recurrence scores on chemotherapy utilization in a multi-institutional breast cancer cohort. Breast Cancer Res Treat 126(797):802

    Google Scholar 

  22. Habel LA, Shak S, Jacobs MK et al (2006) A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Res 8:R25

    Article  PubMed  Google Scholar 

  23. Kamal AH, Loprinzi CL, Reynolds C et al (2007) How well do standard prognostic criteria predict oncotype DX (ODX) scores? J Clin Oncol 25:18s

    Google Scholar 

  24. Asad J, Jacobson AF, Estabrook MD et al (2008) Does oncotype DX recurrence score affect the management of patients with early-stage breast cancer? Am J Surg 196:527–529

    Article  PubMed  Google Scholar 

  25. Erb C, Fox KR, Patel M, et al. (2007) Evaluation of practice patterns in the treatment of node-negative, hormone-receptor positive breast cancer patients with the use of the Oncotype DX assay at the University of Pennsylvania. Presented at the 30th Annual San Antonio Breast Cancer Symposium. December 13–16, 2007; San Antonio, TX. Abstract #3082

  26. Klang S, Liebermann N, Rizel L et al (2010) The recurrence score and chemotherapy treatment in node-positive, ER+ early-stage breast cancer patients in Israel (Abstract). J Clin Oncol 28:15s

    Google Scholar 

  27. 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 randomized trials. Lancet 365:1687–1717

    Article  Google Scholar 

  28. Statistics Canada. Life Tables—Canada, provinces and territories, 1995–1997. Cat. No. 84–537. Government of Canada. 2003 Statistics, Canada

  29. Smith RE, Bryant J, DeCillis A, Anderson S (2003) Acute myeloid leukemia and myelodysplastic syndrome after doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: the national surgical adjuvant breast and bowel project experience. J Clin Oncol 21:1195–1204

    Article  PubMed  CAS  Google Scholar 

  30. Younis T, Rayson D, Sellon M, Skedgel C (2008) Adjuvant chemotherapy for breast cancer: a cost-utility analysis of FEC-D vs. FEC 100. Breast Cancer Res Treat 111:261–267

    Article  PubMed  CAS  Google Scholar 

  31. Younis T, Rayson D, Skedgel C (2012) The cost utility of adjuvant chemotherapy with docetaxel and cyclophosphamide compared with adriamycin and cyclophosphamide in breast cancer. Curr Oncol 18(6):e288–e296

    Google Scholar 

  32. Diamandidou E, Buzdar AU, Smith TL, Frye D, Witjaksono M, Hortobagyi GN (1996) Treatment-related leukemia in breast cancer patients treated with fluorouracil-doxorubicin-cyclophosphamide combination adjuvant chemotherapy: the University of Texas M.D. Anderson Cancer Center experience. J Clin Oncol 14:2722–2730

    PubMed  CAS  Google Scholar 

  33. Swain SM, Whaley FS, Ewer MS (2003) Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 97:2869–2879

    Article  PubMed  CAS  Google Scholar 

  34. Towns K, Bedard PL, Verma S (2008) Matters of the heart: cardiac toxicity of adjuvant systemic therapy for early-stage breast cancer. Curr Oncol 15:S16–S29

    Article  PubMed  CAS  Google Scholar 

  35. Skedgel C, Rayson D, Dewar R et al (2007) Cost-utility of adjuvant hormone therapies for breast cancer in post-menopausal women: sequential tamoxifen-exemestane and upfront anastrazole. Breast Cancer Res Treat 101:325–333

    Article  PubMed  CAS  Google Scholar 

  36. Younis T, Rayson D, Dewar R et al (2007) Modeling for cost effective adjuvant aromatase inhibitor strategies for post-menopausal women with breast cancer. Ann Oncol 18:293–298

    Article  PubMed  CAS  Google Scholar 

  37. Skedgel C, Rayson D, Younis T (2009) The cost-utility of sequential adjuvant trastuzumab in women with Her2/Neu-positive breast cancer: an analysis based on updated results from the HERA trial. Value Health 12:641–648

    Article  PubMed  Google Scholar 

  38. Bonneterre J, Roche H, Kerbrat P et al (2005) Epirubicin increases long-term survival in adjuvant chemotherapy of patients with poor-prognosis, node-positive, early breast cancer: 10-year follow-up results of the French adjuvant study group 05 randomized trial. J Clin Oncol 23:2686–2693

    Article  PubMed  CAS  Google Scholar 

  39. Roche H, Fumoleau P, Spielman M et al (2006) Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 trial. J Clin Oncol 24:5664–5671

    Article  PubMed  CAS  Google Scholar 

  40. 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 36:724–735

    Article  PubMed  CAS  Google Scholar 

  41. Tufts-New England Medical Center, Institute for Clinical Research and Health Policy Studies: The CEA Registry. Available at https://research.tufts-nemc.org/cear/Default.aspx. Cited 5 Aug 2010

  42. Tengs TO, Wallace A (2000) One thousand health-related quality-of-life estimates. Med Care 38:583–637

    Article  PubMed  CAS  Google Scholar 

  43. Ward S, Simpson E, Davis S, Hind D, Rees A, Wilkinson A (2007) Taxanes for the adjuvant treatment of early breast cancer: systematic review and economic evaluation. Health Technol Assess 11:1–144

    Google Scholar 

  44. Lachaine J, Yelle L, Kaizer L, Dufour A, Hopkins S, Deuson R (2005) Chemotherapy-induced emesis: quality of life and economic impact in the context of current practice in Canada. Support Cancer Ther 2:181–187

    Article  PubMed  Google Scholar 

  45. Dranitsaris G, Tran TM, McGeer A, Narine L (1995) Pharmacoeconomic analysis of empirical therapy with ceftazidime alone or combination antibiotics for febrile neutropenia in cancer patients. Pharmacoeconomics 7:49–62

    Article  PubMed  CAS  Google Scholar 

  46. Launois R, Reboul-Marty J, Henry B, Bonneterre J (1996) A cost–utility analysis of second-line chemotherapy in metastatic breast cancer. Docetaxel versus paclitaxel versus vinorelbine. Pharmacoeconomics 10:504–521

    Article  PubMed  CAS  Google Scholar 

  47. Kasteng F, Sobocki P, Svedman C, Lundkvist J (2007) Economic evaluations of leukemia: a review of the literature. Int J Technol Assess Health Care 23:43–53

    Article  PubMed  Google Scholar 

  48. Levy AR, Briggs AH, Demers C, O’Brien BJ (2001) Cost-effectiveness of beta-blocker therapy with metoprolol or with carvedilol for treatment of heart failure in Canada. Am Heart J 142:537–543

    Article  PubMed  CAS  Google Scholar 

  49. Barr R, Furlong W, Henwood J et al (1996) Economic evaluation of allogeneic bone marrow transplantation: a rudimentary model to generate estimates for the timely formulation of clinical policy. J Clin Oncol 14:1413–1420

    PubMed  CAS  Google Scholar 

  50. Sullivan PW, Ghushchyan V (2006) Preference-based EQ-5D index scores for chronic conditions in the United States. Med Decis Mak 26:410–420

    Article  Google Scholar 

  51. Statistics Canada. Consumer Price Index (Health Care). Available at http://cansim2.statcan.ca/cgi-win/cnsmcgi.exe?Lang=E&RootDir=CII/&ResultTemplate=CII/CII_pick&Array_Pick=1&ArrayId=326-0002. Cited 1 Aug 2010

  52. Hirth RA, Chernew ME, Miller E, Fendrick AM, Weissert WG (2000) Willingness to pay for a quality-adjusted life year: in search of a standard. Med Decis Mak 20:332–342

    Article  CAS  Google Scholar 

  53. Mason H, Baker R, Donaldson C (2008) Willingness to pay for a QALY: past, present and future. Expert Rev Pharmacoecon Outcomes Res 8:575–582

    Article  PubMed  Google Scholar 

  54. Meropol NJ, Schrag D, Smith TJ et al (2009) American society of clinical oncology guidance statement: the cost of cancer care. J Clin Oncol 27:3868–3874

    Article  PubMed  Google Scholar 

  55. Greenberg D, Earle C, Fang CH, Eldar-Lissai A, Neumann PJ (2010) When is cancer care cost-effective? A systematic overview of cost-utility analyses in oncology. J Natl Cancer Inst 102:82–88

    Article  PubMed  Google Scholar 

  56. Sridhara R, Johnson JR, Justice R, Keegan P, Chakravarty A, Pazdur R (2010) Review of oncology and hematology drug product approvals at the US food and drug administration between July 2005 and December 2007. J Natl Cancer Inst 102:230–243

    Article  PubMed  Google Scholar 

  57. Murray CJ, Evans DB, Acharya A, Baltussen RM (2000) Development of WHO guidelines on generalized cost-effectiveness analysis. Health Econ 9:235–251

    Article  PubMed  CAS  Google Scholar 

  58. Vanderlaan BF, Broder MS, Chang EY, Oratz R, Bentley TGK (2011) Cost-effectiveness of 21-gene assay in node-positive, early-stage breast cancer. Am J Manag Care 17:455–464

    PubMed  Google Scholar 

  59. Zujewski JA, Kamin L (2008) Trial assessing individualized options for treatment for breast cancer: the TAILORx trial. Future Oncol 4:603–610

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study has been supported by the Canadian Breast Cancer Foundation—Atlantic Chapter. The authors would like to thank Mrs. Marlene Sellon for her help with drug costing.

Conflict of interest

The authors have no conflict of interest to declare. The CU study was not supported by pharmaceutical companies or Genomic Health, Inc.

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Authors and Affiliations

  1. Department of Medicine, Dalhousie University, 454 Bethune Building. 1276 South Park Street, Halifax, NS, B3H 2Y9, Canada

    Nathan W. D. Lamond, Daniel Rayson & Tallal Younis

  2. Atlantic Clinical Cancer Research Unit (ACCRU) at the Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada

    Chris Skedgel, Daniel Rayson & Tallal Younis

  3. Department of Community Health and Epidemiology, Dalhousie University, Halifax, NS, Canada

    Lynn Lethbridge

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  1. Nathan W. D. Lamond
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  2. Chris Skedgel
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Correspondence to Tallal Younis.

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10549_2012_1989_MOESM1_ESM.tif

Online Resource Figure 1: Incremental Costs and QALYs in Node-negative and node-positive Breast Cancer. The Y axis shows the incremental costs (in $) associated with RS testing, while the X axis shows the incremental QALYs gained. Abbreviations – RS: recurrence score. QALY: quality-adjusted life year (TIFF 161 kb)

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Lamond, N.W.D., Skedgel, C., Rayson, D. et al. Cost-utility of the 21-gene recurrence score assay in node-negative and node-positive breast cancer. Breast Cancer Res Treat 133, 1115–1123 (2012). https://doi.org/10.1007/s10549-012-1989-5

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  • DOI: https://doi.org/10.1007/s10549-012-1989-5

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