Journal Article
. 2018 Mar;10().
doi: 10.2147/CEOR.S146095.

Clinical and economic impact of the 21-gene recurrence score assay in adjuvant therapy decision making in patients with early-stage breast cancer: pooled analysis in 4 Basque Country university hospitals

Purificación Martínez Del Prado 1 Isabel Alvarez-López 2 Severina Domínguez-Fernández 3 Arrate Plazaola 4 Oliver Ibarrondo 5 Elena Galve-Calvo 1 Nerea Ancizar-Lizarraga 2 María Gutierrez-Toribio 3 Ainhara Lahuerta-Martínez 4 Javier Mar 5 
  • PMID: 29593426
  •     29 References
  •     3 citations


Purpose: The 21-gene recurrence score (RS) is a genomic test developed as a prognostic and predictive tool to improve the treatment decision making in cases of estrogen receptor-positive and human epidermal growth factor receptor 2-negative early-stage breast cancer. This study examined the clinical and economic impact of its use in 4 Basque Country university hospitals.

Methods: Taking into consideration the RS result, we recorded the recommended initial systemic adjuvant therapy (endocrine therapy with or without chemotherapy) according to standard clinicopathologic factors and the final decision about chemotherapy. Then, if the RS was high, chemotherapy was recommended; it was not recommended if the RS was low; for those with an intermediate RS, clinicopathologic factors were considered, and the initial recommendation based on those factors was maintained. In addition, the probability of switching treatment was calculated. Then, we developed an economic evaluation by measuring the treatment's incremental short-term budget impact from both the societal perspective and that of the Basque Health System. Patients' characteristics and chemotherapy use were analyzed using logistic regressions and receiver operating characteristic curves.

Results: Without an RS, chemotherapy would have been prescribed to 56% of 401 patients, but, with RS use, that percentage decreased to 25. The overall rate of decision change was 35.4%. Test inclusion led to a reduction in chemotherapy costs of €922 per patient in the total population. Although this reduction did not entirely offset the cost of the test, the productivity loss per patient was reduced by €1,977.

Conclusion: The 21-gene RS test significantly changed the indication for chemotherapy. As chemotherapy treatments with no benefit were avoided, patients' quality of life was improved. The short-term economic impact was negative for the Basque Health Service, but savings resulted when sick-leave costs were included.

Keywords: 21-gene assay; adjuvant chemotherapy; early-stage breast cancer; economic evaluation; health care costs.

Tailoring therapies--improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015.
A S Coates, E P Winer, +6 authors, Panel Members.
Ann Oncol, 2015 May 06; 26(8). PMID: 25939896    Free PMC article.
Highly Cited.
Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer.
Aleix Prat, Maggie Chon U Cheang, +8 authors, Charles M Perou.
J Clin Oncol, 2012 Dec 13; 31(2). PMID: 23233704    Free PMC article.
Highly Cited.
A method of comparing the areas under receiver operating characteristic curves derived from the same cases.
J A Hanley, B J McNeil.
Radiology, 1983 Sep 01; 148(3). PMID: 6878708
Highly Cited.
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.
Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG), C Davies, +11 authors, R Peto.
Lancet, 2011 Aug 02; 378(9793). PMID: 21802721    Free PMC article.
Highly Cited.
Perspectives in economic evaluation.
S Byford, J Raftery.
BMJ, 1998 Jun 06; 316(7143). PMID: 9582152    Free PMC article.
The impact of a genomic assay (Oncotype DX) on adjuvant treatment recommendations in early breast cancer.
Richard H de Boer, Caroline Baker, +3 authors, G Bruce Mann.
Med J Aust, 2013 Aug 06; 199(3). PMID: 23909545
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 meaning and use of the area under a receiver operating characteristic (ROC) curve.
J A Hanley, B J McNeil.
Radiology, 1982 Apr 01; 143(1). PMID: 7063747
Highly Cited.
Prospective transGEICAM study of the impact of the 21-gene Recurrence Score assay and traditional clinicopathological factors on adjuvant clinical decision making in women with estrogen receptor-positive (ER+) node-negative breast cancer.
J Albanell, A González, +17 authors, A Lluch.
Ann Oncol, 2011 Jun 10; 23(3). PMID: 21652577
Multigene assays and molecular markers in breast cancer: systematic review of health economic analyses.
Roman Rouzier, Paolo Pronzato, +3 authors, William J Valentine.
Breast Cancer Res Treat, 2013 Jun 01; 139(3). PMID: 23722312    Free PMC article.
Systematic Review.
Molecular and protein markers for clinical decision making in breast cancer: today and tomorrow.
Nadia Harbeck, Karl Sotlar, Rachel Wuerstlein, Sophie Doisneau-Sixou.
Cancer Treat Rev, 2013 Oct 22; 40(3). PMID: 24138841
Prospective Clinical Utility Study of the Use of the 21-Gene Assay in Adjuvant Clinical Decision Making in Women With Estrogen Receptor-Positive Early Invasive Breast Cancer: Results From the SWITCH Study.
Joseph Gligorov, Xavier B Pivot, +11 authors, Francilian Breast Intergroup.
Oncologist, 2015 Jun 27; 20(8). PMID: 26112003    Free PMC article.
Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.
Lyndsay N Harris, Nofisat Ismaila, +11 authors, American Society of Clinical Oncology.
J Clin Oncol, 2016 Feb 10; 34(10). PMID: 26858339    Free PMC article.
Highly Cited. Review.
Spanish recommendations on economic evaluation of health technologies.
Julio López-Bastida, Juan Oliva, +4 authors, Jaume Puig-Junoy.
Eur J Health Econ, 2010 Apr 21; 11(5). PMID: 20405159
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.
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.
The 21-gene recurrence score assay impacts adjuvant therapy recommendations for ER-positive, node-negative and node-positive early breast cancer resulting in a risk-adapted change in chemotherapy use.
W Eiermann, M Rezai, +13 authors, J Blohmer.
Ann Oncol, 2012 Nov 09; 24(3). PMID: 23136233    Free PMC article.
Recommendations from the EGAPP Working Group: does the use of Oncotype DX tumor gene expression profiling to guide treatment decisions improve outcomes in patients with breast cancer?
Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group*.
Genet Med, 2015 Dec 19; 18(8). PMID: 26681310
Economic impact of 21-gene recurrence score testing on early-stage breast cancer in Ireland.
Lillian Smyth, Geoff Watson, +13 authors, Janice M Walshe.
Breast Cancer Res Treat, 2015 Sep 14; 153(3). PMID: 26364296
21-Gene Recurrence Score Assay As a Predictor of Adjuvant Chemotherapy Administration for Early-Stage Breast Cancer: An Analysis of Use, Therapeutic Implications, and Disparity Profile.
Jagar Jasem, Arya Amini, +4 authors, Peter Kabos.
J Clin Oncol, 2016 Mar 24; 34(17). PMID: 27001563    Free PMC article.
Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
E Senkus, S Kyriakides, +6 authors, ESMO Guidelines Committee.
Ann Oncol, 2015 Sep 01; 26 Suppl 5. PMID: 26314782
Highly Cited.
Challenges in measuring and valuing productivity costs, and their relevance in mood disorders.
Benedikte R Lensberg, Michael F Drummond, +2 authors, Clément François.
Clinicoecon Outcomes Res, 2013 Nov 26; 5. PMID: 24273412    Free PMC article.
Physician survey of the effect of the 21-gene recurrence score assay results on treatment recommendations for patients with lymph node-positive, estrogen receptor-positive breast cancer.
Ruth Oratz, Benjamin Kim, +4 authors, Michael Broder.
J Oncol Pract, 2011 Jul 07; 7(2). PMID: 21731516    Free PMC article.
Proliferation marker Ki-67 in early breast cancer.
Ander Urruticoechea, Ian E Smith, Mitch Dowsett.
J Clin Oncol, 2005 Sep 30; 23(28). PMID: 16192605
Highly Cited. Review.
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.
Kathy S Albain, William E Barlow, +20 authors, Breast Cancer Intergroup of North America.
Lancet Oncol, 2009 Dec 17; 11(1). PMID: 20005174    Free PMC article.
Highly Cited.
Prediction of clinical outcome from primary tamoxifen by expression of biologic markers in breast cancer patients.
J Chang, T J Powles, +5 authors, M Dowsett.
Clin Cancer Res, 2000 Feb 26; 6(2). PMID: 10690547
Molecular pathway identification using biological network-regularized logistic models.
Wen Zhang, Ying-Wooi Wan, +3 authors, Zhandong Liu.
BMC Genomics, 2014 Feb 26; 14 Suppl 8. PMID: 24564637    Free PMC article.
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.
Personalised medicine and the decision to withhold chemotherapy in early breast cancer with intermediate risk of recurrence - a systematic review and meta-analysis.
Susanna M Wallerstedt, Astrid Nilsson Ek, +3 authors, Barbro Linderholm.
Eur J Clin Pharmacol, 2020 Jun 07; 76(9). PMID: 32504183    Free PMC article.
Clinical analysis of 21-gene recurrence score test in hormone receptor-positive early-stage breast cancer.
Lizhe Zhu, Nan Ma, +5 authors, Yu Ren.
Oncol Lett, 2019 Jun 13; 17(6). PMID: 31186766    Free PMC article.