Journal Article
. 2016 Oct;10().
doi: 10.3332/ecancer.2016.675.

The analytical validation of the Oncotype DX Recurrence Score assay

Frederick L Baehner 1 
Affiliations
  • PMID: 27729940
  •     24 References
  •     4 citations

Abstract

In vitro diagnostic multivariate index assays are highly complex molecular assays that can provide clinically actionable information regarding the underlying tumour biology and facilitate personalised treatment. These assays are only useful in clinical practice if all of the following are established: analytical validation (i.e., how accurately/reliably the assay measures the molecular characteristics), clinical validation (i.e., how consistently/accurately the test detects/predicts the outcomes of interest), and clinical utility (i.e., how likely the test is to significantly improve patient outcomes). In considering the use of these assays, clinicians often focus primarily on the clinical validity/utility; however, the analytical validity of an assay (e.g., its accuracy, reproducibility, and standardisation) should also be evaluated and carefully considered. This review focuses on the rigorous analytical validation and performance of the Oncotype DX® Breast Cancer Assay, which is performed at the Central Clinical Reference Laboratory of Genomic Health, Inc. The assay process includes tumour tissue enrichment (if needed), RNA extraction, gene expression quantitation (using a gene panel consisting of 16 cancer genes plus 5 reference genes and quantitative real-time RT-PCR), and an automated computer algorithm to produce a Recurrence Score® result (scale: 0-100). This review presents evidence showing that the Recurrence Score result reported for each patient falls within a tight clinically relevant confidence interval. Specifically, the review discusses how the development of the assay was designed to optimise assay performance, presents data supporting its analytical validity, and describes the quality control and assurance programmes that ensure optimal test performance over time.

Keywords: Oncotype DX; Recurrence Score; analytical validation; breast cancer; prognostic factor.

Analytical validation of the Oncotype DX genomic diagnostic test for recurrence prognosis and therapeutic response prediction in node-negative, estrogen receptor-positive breast cancer.
Maureen Cronin, Chithra Sangli, +7 authors, Drew Watson.
Clin Chem, 2007 Apr 28; 53(6). PMID: 17463177
Highly Cited.
Challenges and opportunities for oncology biomarker discovery.
Avisek Deyati, Erfan Younesi, Martin Hofmann-Apitius, Natalia Novac.
Drug Discov Today, 2013 Jan 03; 18(13-14). PMID: 23280501
Review.
Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes.
Jo Vandesompele, Katleen De Preter, +4 authors, Frank Speleman.
Genome Biol, 2002 Aug 20; 3(7). PMID: 12184808    Free PMC article.
Highly Cited.
Quantitative expression profiling in formalin-fixed paraffin-embedded samples by affymetrix microarrays.
Diana Abdueva, Michele Wing, +2 authors, Elai Davicioni.
J Mol Diagn, 2010 Jun 05; 12(4). PMID: 20522636    Free PMC article.
Real-time PCR for mRNA quantitation.
Marisa L Wong, Juan F Medrano.
Biotechniques, 2005 Aug 03; 39(1). PMID: 16060372
Highly Cited. Review.
Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update.
Antonio C Wolff, M Elizabeth H Hammond, +19 authors, College of American Pathologists.
Arch Pathol Lab Med, 2013 Oct 09; 138(2). PMID: 24099077    Free PMC article.
Highly Cited.
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.
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.
Excavation of a buried treasure--DNA, mRNA, miRNA and protein analysis in formalin fixed, paraffin embedded tissues.
R Klopfleisch, A T A Weiss, A D Gruber.
Histol Histopathol, 2011 Apr 08; 26(6). PMID: 21472693
Review.
American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer.
Antonio C Wolff, M Elizabeth H Hammond, +22 authors, College of American Pathologists.
J Clin Oncol, 2006 Dec 13; 25(1). PMID: 17159189
Highly Cited.
Consistency of staining and reporting of oestrogen receptor immunocytochemistry within the European Union--an inter-laboratory study.
C A Wells, J P Sloane, +37 authors, European Working Group for Breast Screening Pathology.
Virchows Arch, 2004 Jun 29; 445(2). PMID: 15221370
Reliability of immunohistochemical demonstration of oestrogen receptors in routine practice: interlaboratory variance in the sensitivity of detection and evaluation of scoring systems.
A Rhodes, B Jasani, +2 authors, K D Miller.
J Clin Pathol, 2000 Apr 18; 53(2). PMID: 10767828    Free PMC article.
Multiplexed measurements of gene signatures in different analytes using the Nanostring nCounter Assay System.
Vladislav A Malkov, Kyle A Serikawa, +4 authors, Thomas Fare.
BMC Res Notes, 2009 May 12; 2. PMID: 19426535    Free PMC article.
Human epidermal growth factor receptor 2 assessment in a case-control study: comparison of fluorescence in situ hybridization and quantitative reverse transcription polymerase chain reaction performed by central laboratories.
Frederick L Baehner, Ninah Achacoso, +5 authors, Laurel A Habel.
J Clin Oncol, 2010 Aug 11; 28(28). PMID: 20697093
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.
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
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.
Contribution of cell culture, RNA extraction, and reverse transcription to the measurement error in quantitative reverse transcription polymerase chain reaction-based gene expression quantification.
Jean-Damien Combes, Gaël Grelier, +5 authors, Caroline Moyret-Lalle.
Anal Biochem, 2009 Jun 17; 393(1). PMID: 19527676
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
Estrogen- and progesterone-receptor status in ECOG 2197: comparison of immunohistochemistry by local and central laboratories and quantitative reverse transcription polymerase chain reaction by central laboratory.
Sunil S Badve, Frederick L Baehner, +13 authors, Joseph A Sparano.
J Clin Oncol, 2008 May 20; 26(15). PMID: 18487567
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.
Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features.
Lori J Goldstein, Robert Gray, +12 authors, Joseph A Sparano.
J Clin Oncol, 2008 Aug 06; 26(25). PMID: 18678838    Free PMC article.
Highly Cited.
American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer.
M Elizabeth H Hammond, Daniel F Hayes, +29 authors, Antonio C Wolff.
J Clin Oncol, 2010 Apr 21; 28(16). PMID: 20404251    Free PMC article.
Highly Cited. Systematic Review.
Measurement of gene expression in archival paraffin-embedded tissues: development and performance of a 92-gene reverse transcriptase-polymerase chain reaction assay.
Maureen Cronin, Mylan Pho, +5 authors, Joffre B Baker.
Am J Pathol, 2003 Dec 26; 164(1). PMID: 14695316    Free PMC article.
Highly Cited.
An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper®.
Zsuzsanna Varga, Annette Lebeau, +18 authors, Giuseppe Viale.
Breast Cancer Res, 2017 May 12; 19(1). PMID: 28490348    Free PMC article.
Advances in Precision Health and Emerging Diagnostics for Women.
Megan B Fitzpatrick, Avnesh S Thakor.
J Clin Med, 2019 Sep 25; 8(10). PMID: 31547515    Free PMC article.
Review.
Next generation sequencing of PD-L1 for predicting response to immune checkpoint inhibitors.
Jeffrey M Conroy, Sarabjot Pabla, +37 authors, Carl Morrison.
J Immunother Cancer, 2019 Jan 27; 7(1). PMID: 30678715    Free PMC article.
Molecular characterization of breast cancer needle core biopsy specimens by the 21-gene Breast Recurrence Score test.
Debbie M Jakubowski, Helen Bailey, +7 authors, Frederick L Baehner.
J Surg Oncol, 2020 Jun 05;. PMID: 32497318    Free PMC article.