Journal Article
. 2012 Oct;12().
doi: 10.1186/1471-2407-12-447.

Cost-effectiveness of a 21-gene recurrence score assay versus Canadian clinical practice in women with early-stage estrogen- or progesterone-receptor-positive, axillary lymph-node negative breast cancer

Malek B Hannouf 1 Bin Xie  Muriel Brackstone  Gregory S Zaric  
  • PMID: 23031196
  •     57 References
  •     11 citations


Background: A 21-gene recurrence score (RS) assay may inform adjuvant systematic treatment decisions in women with early stage breast cancer. We sought to investigate the cost effectiveness of using the RS-assay versus current clinical practice (CCP) in women with early-stage estrogen- or progesterone-receptor-positive, axilliary lymph-node negative breast cancer (ER+/ PR + LN- ESBC) from the perspective of the Canadian public healthcare system.

Methods: We developed a Markov model to project the lifetime clinical and economic consequences of ESBC. We evaluated adjuvant therapy separately in post- and pre-menopausal women with ER+/ PR + LN- ESBC. We assumed that the RS-assay would reclassify pre- and post-menopausal women among risk levels (low, intermediate and high) and guide adjuvant systematic treatment decisions. The model was parameterized using 7 year follow up data from the Manitoba Cancer Registry, cost data from Manitoba administrative databases, and secondary sources. Costs are presented in 2010 CAD. Future costs and benefits were discounted at 5%.

Results: The RS-assay compared to CCP generated cost-savings in pre-menopausal women and had an ICER of $60,000 per QALY gained in post-menopausal women. The cost effectiveness was most sensitive to the proportion of women classified as intermediate risk by the RS-assay who receive adjuvant chemotherapy and the risk of relapse in the RS-assay model.

Conclusions: The RS-assay is likely to be cost effective in the Canadian healthcare system and should be considered for adoption in women with ER+/ PR + LN- ESBC. However, ongoing assessment and validation of the assay in real-world clinical practice is warranted.

Breast cancer and prognostic factors. Tumour size, degree of differentiation, proliferation kinetics and expression of steroid hormone receptors.
D Mink, B von Tongelen, +2 authors, W Schmidt.
Eur J Gynaecol Oncol, 1994 Jan 01; 15(6). PMID: 7875157
Lymphatic invasion, tumor size, and age are independent predictors of axillary lymph node metastases in women with T1 breast cancers.
C Gajdos, P I Tartter, I J Bleiweiss.
Ann Surg, 1999 Nov 24; 230(5). PMID: 10561094    Free PMC article.
Economic analysis of targeting chemotherapy using a 21-gene RT-PCR assay in lymph-node-negative, estrogen-receptor-positive, early-stage breast cancer.
John Hornberger, Leon E Cosler, Gary H Lyman.
Am J Manag Care, 2005 May 19; 11(5). PMID: 15898220
Cost-effectiveness analysis of recurrence score-guided treatment using a 21-gene assay in early breast cancer.
Daphne T Tsoi, Miho Inoue, +2 authors, Kathleen I Pritchard.
Oncologist, 2010 Apr 28; 15(5). PMID: 20421264    Free PMC article.
Does oncotype DX recurrence score affect the management of patients with early-stage breast cancer?
Juhi Asad, Allyson F Jacobson, +7 authors, Paul I Tartter.
Am J Surg, 2008 Sep 24; 196(4). PMID: 18809056
Dollars may not buy as many QALYs as we think: a problem with defining quality-of-life adjustments.
D G Fryback, W F Lawrence.
Med Decis Making, 1997 Jul 01; 17(3). PMID: 9219187
How do cost-effectiveness analyses inform reimbursement decisions for oncology medicines in Canada? The example of sunitinib for first-line treatment of metastatic renal cell carcinoma.
Isabelle Chabot, Angela Rocchi.
Value Health, 2010 Jun 22; 13(6). PMID: 20561332
Histopathologic variables predict Oncotype DX recurrence score.
Melina B Flanagan, David J Dabbs, +2 authors, Rohit Bhargava.
Mod Pathol, 2008 Mar 25; 21(10). PMID: 18360352
Randomized, controlled trial of cyclophosphamide, methotrexate, and fluorouracil versus cyclophosphamide, doxorubicin, and fluorouracil with and without tamoxifen for high-risk, node-negative breast cancer: treatment results of Intergroup Protocol INT-0102.
Laura F Hutchins, Stephanie J Green, +7 authors, C Kent Osborne.
J Clin Oncol, 2005 Nov 19; 23(33). PMID: 16293862
Frequency and cost of chemotherapy-related serious adverse effects in a population sample of women with breast cancer.
Michael J Hassett, A James O'Malley, +2 authors, Craig C Earle.
J Natl Cancer Inst, 2006 Aug 17; 98(16). PMID: 16912263
Highly Cited.
Should the elderly receive chemotherapy for node-negative breast cancer? A cost-effectiveness analysis examining total and active life-expectancy outcomes.
C E Desch, B E Hillner, T J Smith, S M Retchin.
J Clin Oncol, 1993 Apr 01; 11(4). PMID: 8478671
Side effects of adjuvant treatment of breast cancer.
C L Shapiro, A Recht.
N Engl J Med, 2001 Jun 30; 344(26). PMID: 11430330
Highly Cited. Review.
Adjuvant docetaxel for high-risk, node-negative breast cancer.
Miguel Martín, Miguel A Seguí, +29 authors, GEICAM 9805 Investigators.
N Engl J Med, 2010 Dec 03; 363(23). PMID: 21121833
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
D J Slamon, G M Clark, +3 authors, W L McGuire.
Science, 1987 Jan 09; 235(4785). PMID: 3798106
Highly Cited.
The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor.
A L Schechter, M C Hung, +5 authors, L Coussens.
Science, 1985 Sep 06; 229(4717). PMID: 2992090
Highly Cited.
Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection.
Shelly S Lo, Patricia B Mumby, +8 authors, Kathy S Albain.
J Clin Oncol, 2010 Jan 13; 28(10). PMID: 20065191
Highly Cited.
The role of economic evidence in Canadian oncology reimbursement decision-making: to lambda and beyond.
Angela Rocchi, Devidas Menon, Shailendra Verma, Elizabeth Miller.
Value Health, 2008 Jan 09; 11(4). PMID: 18179658
A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
M E Charlson, P Pompei, K L Ales, C R MacKenzie.
J Chronic Dis, 1987 Jan 01; 40(5). PMID: 3558716
Highly Cited.
Docetaxel in combination with doxorubicin and cyclophosphamide as adjuvant treatment for early node-positive breast cancer: a cost-effectiveness and cost-utility analysis.
Sorrel E Wolowacz, David A Cameron, Helen C Tate, Adrian Bagust.
J Clin Oncol, 2008 Feb 19; 26(6). PMID: 18281666
Survival and treatment patterns in elderly patients with advanced non-small-cell lung cancer in Manitoba.
C L Baunemann Ott, N Ratna, +3 authors, S Navaratnam.
Curr Oncol, 2011 Oct 08; 18(5). PMID: 21980255    Free PMC article.
Adjuvant chemotherapy for early breast cancer: optimal use of epirubicin.
Stefan Glück.
Oncologist, 2005 Nov 30; 10(10). PMID: 16314288
Assessing the clinical impact of prognostic factors: when is "statistically significant" clinically useful?
D F Hayes, B Trock, A L Harris.
Breast Cancer Res Treat, 1999 Mar 05; 52(1-3). PMID: 10066089
Trial assessing individualized options for treatment for breast cancer: the TAILORx trial.
Jo Anne Zujewski, Leah Kamin.
Future Oncol, 2008 Oct 17; 4(5). PMID: 18922117
Economic evaluation of 21-gene reverse transcriptase-polymerase chain reaction assay in lymph-node-negative, estrogen-receptor-positive, early-stage breast cancer in Japan.
Masahide Kondo, Shu Ling Hoshi, +2 authors, Masakazu Toi.
Breast Cancer Res Treat, 2007 Dec 14; 112(1). PMID: 18075786
American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer.
Lyndsay Harris, Herbert Fritsche, +7 authors, American Society of Clinical Oncology.
J Clin Oncol, 2007 Oct 24; 25(33). PMID: 17954709
Highly Cited. Review.
Trends in breast cancer by race and ethnicity.
Asma Ghafoor, Ahmedin Jemal, +3 authors, Michael Thun.
CA Cancer J Clin, 2004 Jul 01; 53(6). PMID: 15224974
Tentative guidelines for using clinical and economic evaluations revisited.
A Laupacis, D Feeny, A S Detsky, P X Tugwell.
CMAJ, 1993 Mar 15; 148(6). PMID: 8448707    Free PMC article.
Population-based assessment of hospitalizations for toxicity from chemotherapy in older women with breast cancer.
Xianglin L Du, Cynthia Osborne, James S Goodwin.
J Clin Oncol, 2002 Dec 19; 20(24). PMID: 12488407    Free PMC article.
Is molecular profiling ready for use in clinical decision making?
John P A Ioannidis.
Oncologist, 2007 Apr 05; 12(3). PMID: 17405894
The relationship between prognostic and predictive factors in the management of breast cancer.
I C Henderson, A J Patek.
Breast Cancer Res Treat, 1999 Mar 05; 52(1-3). PMID: 10066087
Doxorubicin in combination with fluorouracil and cyclophosphamide (i.v. FAC regimen, day 1, 21) versus methotrexate in combination with fluorouracil and cyclophosphamide (i.v. CMF regimen, day 1, 21) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group.
M Martin, A Villar, +13 authors, GEICAM Group (Spanish Breast Cancer Research Group), Spain.
Ann Oncol, 2003 Jun 11; 14(6). PMID: 12796019
Radiation treatment waiting times for breast cancer patients in Manitoba, 2001 and 2005.
A L Cooke, R Appell, +2 authors, S Latosinsky.
Curr Oncol, 2009 Oct 29; 16(5). PMID: 19862362    Free PMC article.
Markov models in medical decision making: a practical guide.
F A Sonnenberg, J R Beck.
Med Decis Making, 1993 Oct 01; 13(4). PMID: 8246705
Highly Cited.
Long-term adjustment of survivors of early-stage breast carcinoma, 20 years after adjuvant chemotherapy.
Alice B Kornblith, James E Herndon, +10 authors, Jimmie C Holland.
Cancer, 2003 Aug 12; 98(4). PMID: 12910510
Localization of the human erbB-2 gene on normal and rearranged chromosomes 17 to bands q12-21.32.
N C Popescu, C R King, M H Kraus.
Genomics, 1989 Apr 01; 4(3). PMID: 2565881
Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.
Soonmyung Paik, Gong Tang, +11 authors, Norman Wolmark.
J Clin Oncol, 2006 May 25; 24(23). PMID: 16720680
Highly Cited.
Economic evaluations in the canadian common drug review.
Andreas Laupacis.
Pharmacoeconomics, 2006 Oct 28; 24(11). PMID: 17067199
Tumor gene expression and prognosis in breast cancer patients with 10 or more positive lymph nodes.
Melody A Cobleigh, Bita Tabesh, +7 authors, Steven Shak.
Clin Cancer Res, 2005 Dec 20; 11(24 Pt 1). PMID: 16361546
Comparison of treatment received versus long-standing guidelines for stage III colon and stage II/III rectal cancer patients diagnosed in Alberta, Saskatchewan, and Manitoba in 2004.
Marilyn Cree, Jon Tonita, +5 authors, Marcy Winget.
Clin Colorectal Cancer, 2009 Jul 28; 8(3). PMID: 19632928
A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.
Soonmyung Paik, Steven Shak, +12 authors, Norman Wolmark.
N Engl J Med, 2004 Dec 14; 351(27). PMID: 15591335
Highly Cited.
Amplification of c-erbB-2 and aggressive human breast tumors?
D J Slamon, G M Clark.
Science, 1988 Jun 24; 240(4860). PMID: 3289120
Adjuvant systemic therapy for women with node-negative breast cancer. The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer.
CMAJ, 1998 Mar 04; 158 Suppl 3. PMID: 9484278
Systematic Review.
Gene expression profiling for guiding adjuvant chemotherapy decisions in women with early breast cancer: an evidence-based and economic analysis.
Medical Advisory Secretariat.
Ont Health Technol Assess Ser, 2010 Jan 01; 10(23). PMID: 23074401    Free PMC article.
The efficacy and cost-effectiveness of adjuvant therapy of early breast cancer in premenopausal women.
T J Smith, B E Hillner.
J Clin Oncol, 1993 Apr 01; 11(4). PMID: 8478670
Health economics in drug development: efficient research to inform healthcare funding decisions.
Peter S Hall, Christopher McCabe, Julia M Brown, David A Cameron.
Eur J Cancer, 2010 Jul 27; 46(15). PMID: 20655197
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.
Gary H Lyman, Leon E Cosler, Nicole M Kuderer, John Hornberger.
Cancer, 2007 Feb 22; 109(6). PMID: 17311307
Impact of a commercial reference laboratory test recurrence score on decision making in early-stage breast cancer.
Ruth Oratz, Dev Paul, Allen L Cohn, Scot M Sedlacek.
J Oncol Pract, 2007 Jul 01; 3(4). PMID: 20859407    Free PMC article.
Canadian breast cancer guidelines: have they made a difference?
Steven Latosinsky, Katherine Fradette, +2 authors, Donna Turner.
CMAJ, 2007 Mar 14; 176(6). PMID: 17353529    Free PMC article.
Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20.
Eleftherios P Mamounas, Gong Tang, +7 authors, Norman Wolmark.
J Clin Oncol, 2010 Jan 13; 28(10). PMID: 20065188    Free PMC article.
Highly Cited.
Economic evaluation of sorafenib in the treatment of hepatocellular carcinoma in Canada.
Noemi Muszbek, Sonalee Shah, +4 authors, Jennifer Knox.
Curr Med Res Opin, 2008 Nov 27; 24(12). PMID: 19032137
Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG).
Lancet, 2005 May 17; 365(9472). PMID: 15894097
Highly Cited.
Systematic overview of cost-utility assessments in oncology.
C C Earle, R H Chapman, +4 authors, P J Neumann.
J Clin Oncol, 2000 Sep 14; 18(18). PMID: 10986064
Cost-utility of the 21-gene recurrence score assay in node-negative and node-positive breast cancer.
Nathan W D Lamond, Chris Skedgel, +2 authors, Tallal Younis.
Breast Cancer Res Treat, 2012 Mar 01; 133(3). PMID: 22361999
Economic implications of 21-gene breast cancer risk assay from the perspective of an Israeli-managed health-care organization.
Shmuel H Klang, Ariel Hammerman, +3 authors, John Hornberger.
Value Health, 2010 Apr 24; 13(4). PMID: 20412544
Report of nationally representative values for the noninstitutionalized US adult population for 7 health-related quality-of-life scores.
Janel Hanmer, William F Lawrence, +2 authors, Dennis G Fryback.
Med Decis Making, 2006 Jul 21; 26(4). PMID: 16855127
Highly Cited.
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).
Masahide Kondo, Shu-Ling Hoshi, +2 authors, Masakazu Toi.
Breast Cancer Res Treat, 2010 Nov 18; 127(3). PMID: 21082239
Higher efficacy of letrozole in combination with trastuzumab compared to letrozole monotherapy as first-line treatment in patients with HER2-positive, hormone-receptor-positive metastatic breast cancer - results of the eLEcTRA trial.
J Huober, P A Fasching, +13 authors, N Harbeck.
Breast, 2011 Aug 25; 21(1). PMID: 21862331
Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013.
A Goldhirsch, E P Winer, +5 authors, Panel members.
Ann Oncol, 2013 Aug 07; 24(9). PMID: 23917950    Free PMC article.
Highly Cited.
Cost effectiveness of a 21-gene recurrence score assay versus Canadian clinical practice in post-menopausal women with early-stage estrogen or progesterone-receptor-positive, axillary lymph-node positive breast cancer.
Malek B Hannouf, Bin Xie, Muriel Brackstone, Gregory S Zaric.
Pharmacoeconomics, 2013 Nov 30; 32(2). PMID: 24288208
Differential patterns of recurrence and specific survival between luminal A and luminal B breast cancer according to recent changes in the 2013 St Gallen immunohistochemical classification.
A García Fernández, C Chabrera, +11 authors, N Giménez.
Clin Transl Oncol, 2014 Oct 02; 17(3). PMID: 25270605
Cost-effectiveness of using a gene expression profiling test to aid in identifying the primary tumour in patients with cancer of unknown primary.
M B Hannouf, E Winquist, +6 authors, G S Zaric.
Pharmacogenomics J, 2016 Mar 30; 17(3). PMID: 27019982
The Clinical Significance of Occult Gastrointestinal Primary Tumours in Metastatic Cancer: A Population Retrospective Cohort Study.
Malek B Hannouf, Eric Winquist, +6 authors, Gregory S Zaric.
Cancer Res Treat, 2017 Mar 23; 50(1). PMID: 28324922    Free PMC article.
Towards decision-making using individualized risk estimates for personalized medicine: A systematic review of genomic classifiers of solid tumors.
Daniel M Trifiletti, Vanessa N Sturz, Timothy N Showalter, Jennifer M Lobo.
PLoS One, 2017 May 10; 12(5). PMID: 28486497    Free PMC article.
Systematic Review.
Prolaris Cell Cycle Progression Test for Localized Prostate Cancer: A Health Technology Assessment.
Health Quality Ontario.
Ont Health Technol Assess Ser, 2017 Jun 03; 17(6). PMID: 28572867    Free PMC article.
Systematic Review.
The clinical significance of occult gynecologic primary tumours in metastatic cancer.
M B Hannouf, E Winquist, +6 authors, G S Zaric.
Curr Oncol, 2017 Nov 02; 24(5). PMID: 29089807    Free PMC article.
The Potential Clinical and Economic Value of Primary Tumour Identification in Metastatic Cancer of Unknown Primary Tumour: A Population-Based Retrospective Matched Cohort Study.
Malek B Hannouf, Eric Winquist, +6 authors, Gregory S Zaric.
Pharmacoecon Open, 2018 Apr 07; 2(3). PMID: 29623630    Free PMC article.
Cost-Effectiveness Analyses of the 21-Gene Assay in Breast Cancer: Systematic Review and Critical Appraisal.
Shi-Yi Wang, Weixiong Dang, +3 authors, Cary P Gross.
J Clin Oncol, 2018 Apr 17; 36(16). PMID: 29659329    Free PMC article.
Systematic Review.
Gene Expression Profiling Tests for Early-Stage Invasive Breast Cancer: A Health Technology Assessment.
Ontario Health (Quality).
Ont Health Technol Assess Ser, 2020 Apr 15; 20(10). PMID: 32284770    Free PMC article.