Journal Article
. 2015 Nov;32(12).
doi: 10.1007/s12325-015-0269-2.

A Prospective Comparison of the 21-Gene Recurrence Score and the PAM50-Based Prosigna in Estrogen Receptor-Positive Early-Stage Breast Cancer

Michael D Alvarado 1 Che Prasad 2 Megan Rothney 3 Diana B Cherbavaz 3 Amy P Sing 3 Frederick L Baehner 4 Christer Svedman 3 Christos J Markopoulos 5 
Affiliations
  • PMID: 26610383
  •     18 References
  •     12 citations

Abstract

Introduction: The 21-gene Recurrence Score(®) assay (Oncotype DX(®), Genomic Health, Inc.) is a validated predictor of recurrence risk/chemotherapy benefit in patients with estrogen receptor-positive (ER+) early-stage breast cancer treated with endocrine therapy. The Prosigna(®) assay (NanoString Technologies Inc.) is a validated prognosticator in postmenopausal patients with low-risk ER+ early-stage breast cancer treated with endocrine therapy. The assays were analytically/clinically developed and validated differently. This study focused on comparing recurrence risk estimates as determined by these assays and is the first blinded comparison of these assays on matched patient samples.

Methods: Sequential breast cancer specimens from postmenopausal, node-negative, ER+ patients treated at the Marin General Hospital were analyzed: first by the 21-gene assay then by the Prosigna assay in an independent lab blinded to the Recurrence Score results.

Results: The final analysis included 52 patients. Correlation between the Recurrence Score and the Prosigna assay results was poor (r = 0.08). Agreement between risk classifications based on these assays was 54%; 4/7 of patients classified as high risk by the Prosigna assay had low Recurrence Score results. Two tumors with high Recurrence Score results had low ER expression (close to positivity threshold); both of which had a low/intermediate Prosigna assay result. The Prosigna assay classified 73.1% and 23.1% of samples as luminal A and luminal B, respectively. A range of Recurrence Score results was observed within the subtypes; 83% of luminal B samples had a low Recurrence Score result.

Conclusion: Consistent with prior comparisons between the 21-gene and other genomic assays, our study demonstrated substantial differences in the way patients are risk stratified, suggesting that the different assays are not interchangeable.

Funding: Genomic Health, Inc.

Keywords: Adjuvant chemotherapy; Breast cancer; Oncology; Oncotype DX; PAM50; Prosigna, risk assessment; Recurrence Score.

Comparison of PAM50 risk of recurrence score with oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy.
Mitch Dowsett, Ivana Sestak, +7 authors, Jack Cuzick.
J Clin Oncol, 2013 Jul 03; 31(22). PMID: 23816962
Highly Cited.
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.
Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
E Senkus, S Kyriakides, +5 authors, ESMO Guidelines Working Group.
Ann Oncol, 2013 Aug 24; 24 Suppl 6. PMID: 23970019
Highly Cited.
Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone.
M Gnant, M Filipits, +22 authors, Austrian Breast and Colorectal Cancer Study Group.
Ann Oncol, 2013 Dec 19; 25(2). PMID: 24347518
Highly Cited.
Identifying clinically relevant prognostic subgroups of postmenopausal women with node-positive hormone receptor-positive early-stage breast cancer treated with endocrine therapy: a combined analysis of ABCSG-8 and ATAC using the PAM50 risk of recurrence score and intrinsic subtype.
M Gnant, I Sestak, +14 authors, J Cuzick.
Ann Oncol, 2015 May 04; 26(8). PMID: 25935792
Prospective Validation of a 21-Gene Expression Assay in Breast Cancer.
Joseph A Sparano, Robert J Gray, +28 authors, George W Sledge.
N Engl J Med, 2015 Sep 29; 373(21). PMID: 26412349    Free PMC article.
Highly Cited.
Molecular portraits of human breast tumours.
C M Perou, T Sørlie, +15 authors, D Botstein.
Nature, 2000 Aug 30; 406(6797). PMID: 10963602
Highly Cited.
Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications.
T Sørlie, C M Perou, +14 authors, A L Børresen-Dale.
Proc Natl Acad Sci U S A, 2001 Sep 13; 98(19). PMID: 11553815    Free PMC article.
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.
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.
A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients.
Laurel A Habel, Steven Shak, +12 authors, Charles P Quesenberry.
Breast Cancer Res, 2006 Jun 02; 8(3). PMID: 16737553    Free PMC article.
Highly Cited.
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.
Evaluation and validation of total RNA extraction methods for microRNA expression analyses in formalin-fixed, paraffin-embedded tissues.
Martina Doleshal, Amber A Magotra, +3 authors, Anna E Szafranska.
J Mol Diagn, 2008 Apr 12; 10(3). PMID: 18403610    Free PMC article.
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 risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study.
Mitch Dowsett, Jack Cuzick, +11 authors, Steven Shak.
J Clin Oncol, 2010 Mar 10; 28(11). PMID: 20212256
Highly Cited.
Clinical significance of the 21-gene signature (Oncotype DX) in hormone receptor-positive early stage primary breast cancer in the Japanese population.
Masakazu Toi, Hiroji Iwata, +8 authors, Japan Breast Cancer Research Group-Translational Research Group.
Cancer, 2010 Jun 22; 116(13). PMID: 20564629
Utility of prognostic genomic tests in breast cancer practice: The IMPAKT 2012 Working Group Consensus Statement.
H A Azim, S Michiels, +9 authors, C Swanton.
Ann Oncol, 2013 Jan 23; 24(3). PMID: 23337633    Free PMC article.
Comparison of EndoPredict and Oncotype DX test results in hormone receptor positive invasive breast cancer.
Zsuzsanna Varga, Peter Sinn, +6 authors, Holger Moch.
PLoS One, 2013 Mar 19; 8(3). PMID: 23505515    Free PMC article.
Testing chemotherapy efficacy in HER2 negative breast cancer using patient-derived spheroids.
Kathrin Halfter, Oliver Hoffmann, +6 authors, Barbara Mayer.
J Transl Med, 2016 May 05; 14(1). PMID: 27142386    Free PMC article.
Best Practices for Genomic Assay Testing in Early-Stage Breast Cancer: Clinical and Medicolegal Perspectives.
Andrew D Seidman, Darius K Amjadi, Tammy De La Melena, Darren Wheeler.
Popul Health Manag, 2016 Sep 30; 20(4). PMID: 27684734    Free PMC article.
Integrated Analysis Identifies Molecular Signatures and Specific Prognostic Factors for Different Gastric Cancer Subtypes.
Li Min, Yu Zhao, +6 authors, Shutian Zhang.
Transl Oncol, 2016 Dec 26; 10(1). PMID: 28013168    Free PMC article.
Selecting postoperative adjuvant systemic therapy for early stage breast cancer: A critical assessment of commercially available gene expression assays.
David M Hyams, Eric Schuur, +7 authors, Aníbal Nuñez De Pierro.
J Surg Oncol, 2017 Feb 18; 115(6). PMID: 28211064    Free PMC article.
Review.
MammaPrint versus EndoPredict: Poor correlation in disease recurrence risk classification of hormone receptor positive breast cancer.
Andreas Bösl, Andreas Spitzmüller, +3 authors, Felix Offner.
PLoS One, 2017 Aug 30; 12(8). PMID: 28850621    Free PMC article.
Copy number profiling of Oncotype DX genes reveals association with survival of breast cancer patients.
Washaakh Ahmed, Muhammad Faraz Arshad Malik, Muhammad Saeed, Farhan Haq.
Mol Biol Rep, 2018 Sep 19; 45(6). PMID: 30225582
An assessment of prognostic immunity markers in breast cancer.
Benlong Yang, Jeff Chou, +13 authors, Zhiyuan Hu.
NPJ Breast Cancer, 2018 Nov 06; 4. PMID: 30393759    Free PMC article.
Decision of Adjuvant Systemic Treatment in HR+ HER2- Early Invasive Breast Cancer: Which Biomarkers Could Help?
Marie Alexandre, Aurélie Maran-Gonzalez, +6 authors, Séverine Guiu.
Cancer Manag Res, 2019 Dec 19; 11. PMID: 31849525    Free PMC article.
Review.
Oncotype DX Breast Cancer recurrence score resists inter-assay reproducibility with RT2-Profiler Multiplex RT-PCR.
Verena Schildgen, Mathias Warm, Michael Brockmann, Oliver Schildgen.
Sci Rep, 2020 Jan 01; 9(1). PMID: 31889145    Free PMC article.
The Effect of the New Eighth Edition Breast Cancer Staging System on 100 Consecutive Patients.
Ashley Biswal, Jacqueline Erler, +6 authors, Denise Johnson Miller.
J Clin Med Res, 2019 May 31; 11(6). PMID: 31143307    Free PMC article.
Comparison of breast cancer prognostic tests CanAssist Breast and Oncotype DX.
Aditya K Sengupta, Aparna Gunda, +4 authors, Manjiri M Bakre.
Cancer Med, 2020 Oct 08; 9(21). PMID: 33027559    Free PMC article.
Characterization of molecular scores and gene expression signatures in primary breast cancer, local recurrences and brain metastases.
Mariana Bustamante Eduardo, Vlad Popovici, +5 authors, Rolf Jaggi.
BMC Cancer, 2019 Jun 09; 19(1). PMID: 31174485    Free PMC article.