Development and validation for research assessment of Oncotype DX® Breast Recurrence Score, EndoPredict® and Prosigna®

Abstract Multi-gene prognostic signatures including the Oncotype® DX Recurrence Score (RS), EndoPredict® (EP) and Prosigna® (Risk Of Recurrence, ROR) are widely used to predict the likelihood of distant recurrence in patients with oestrogen-receptor-positive (ER+), HER2-negative breast cancer. Here,...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Richard Buus, Zsolt Szijgyarto, Eugene F. Schuster, Hui Xiao, Ben P. Haynes, Ivana Sestak, Jack Cuzick, Laia Paré, Elia Seguí, Nuria Chic, Aleix Prat, Mitch Dowsett, Maggie Chon U. Cheang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/ab6604a1505e46ae8d5a30ae6561a42c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ab6604a1505e46ae8d5a30ae6561a42c
record_format	dspace
spelling	oai:doaj.org-article:ab6604a1505e46ae8d5a30ae6561a42c2021-12-02T14:26:57ZDevelopment and validation for research assessment of Oncotype DX® Breast Recurrence Score, EndoPredict® and Prosigna®10.1038/s41523-021-00216-w2374-4677https://doaj.org/article/ab6604a1505e46ae8d5a30ae6561a42c2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00216-whttps://doaj.org/toc/2374-4677Abstract Multi-gene prognostic signatures including the Oncotype® DX Recurrence Score (RS), EndoPredict® (EP) and Prosigna® (Risk Of Recurrence, ROR) are widely used to predict the likelihood of distant recurrence in patients with oestrogen-receptor-positive (ER+), HER2-negative breast cancer. Here, we describe the development and validation of methods to recapitulate RS, EP and ROR scores from NanoString expression data. RNA was available from 107 tumours from postmenopausal women with early-stage, ER+, HER2− breast cancer from the translational Arimidex, Tamoxifen, Alone or in Combination study (TransATAC) where previously these signatures had been assessed with commercial methodology. Gene expression was measured using NanoString nCounter. For RS and EP, conversion factors to adjust for cross-platform variation were estimated using linear regression. For ROR, the steps to perform subgroup-specific normalisation of the gene expression data and calibration factors to calculate the 46-gene ROR score were assessed and verified. Training with bootstrapping (n = 59) was followed by validation (n = 48) using adjusted, research use only (RUO) NanoString-based algorithms. In the validation set, there was excellent concordance between the RUO scores and their commercial counterparts (r c(RS) = 0.96, 95% CI 0.93–0.97 with level of agreement (LoA) of −7.69 to 8.12; r c(EP) = 0.97, 95% CI 0.96–0.98 with LoA of −0.64 to 1.26 and r c(ROR) = 0.97 (95% CI 0.94–0.98) with LoA of −8.65 to 10.54). There was also a strong agreement in risk stratification: (RS: κ = 0.86, p < 0.0001; EP: κ = 0.87, p < 0.0001; ROR: κ = 0.92, p < 0.001). In conclusion, the calibrated algorithms recapitulate the commercial RS and EP scores on individual biopsies and ROR scores on samples based on subgroup-centreing method using NanoString expression data.Richard BuusZsolt SzijgyartoEugene F. SchusterHui XiaoBen P. HaynesIvana SestakJack CuzickLaia ParéElia SeguíNuria ChicAleix PratMitch DowsettMaggie Chon U. CheangNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Richard Buus Zsolt Szijgyarto Eugene F. Schuster Hui Xiao Ben P. Haynes Ivana Sestak Jack Cuzick Laia Paré Elia Seguí Nuria Chic Aleix Prat Mitch Dowsett Maggie Chon U. Cheang Development and validation for research assessment of Oncotype DX® Breast Recurrence Score, EndoPredict® and Prosigna®
description	Abstract Multi-gene prognostic signatures including the Oncotype® DX Recurrence Score (RS), EndoPredict® (EP) and Prosigna® (Risk Of Recurrence, ROR) are widely used to predict the likelihood of distant recurrence in patients with oestrogen-receptor-positive (ER+), HER2-negative breast cancer. Here, we describe the development and validation of methods to recapitulate RS, EP and ROR scores from NanoString expression data. RNA was available from 107 tumours from postmenopausal women with early-stage, ER+, HER2− breast cancer from the translational Arimidex, Tamoxifen, Alone or in Combination study (TransATAC) where previously these signatures had been assessed with commercial methodology. Gene expression was measured using NanoString nCounter. For RS and EP, conversion factors to adjust for cross-platform variation were estimated using linear regression. For ROR, the steps to perform subgroup-specific normalisation of the gene expression data and calibration factors to calculate the 46-gene ROR score were assessed and verified. Training with bootstrapping (n = 59) was followed by validation (n = 48) using adjusted, research use only (RUO) NanoString-based algorithms. In the validation set, there was excellent concordance between the RUO scores and their commercial counterparts (r c(RS) = 0.96, 95% CI 0.93–0.97 with level of agreement (LoA) of −7.69 to 8.12; r c(EP) = 0.97, 95% CI 0.96–0.98 with LoA of −0.64 to 1.26 and r c(ROR) = 0.97 (95% CI 0.94–0.98) with LoA of −8.65 to 10.54). There was also a strong agreement in risk stratification: (RS: κ = 0.86, p < 0.0001; EP: κ = 0.87, p < 0.0001; ROR: κ = 0.92, p < 0.001). In conclusion, the calibrated algorithms recapitulate the commercial RS and EP scores on individual biopsies and ROR scores on samples based on subgroup-centreing method using NanoString expression data.
format	article
author	Richard Buus Zsolt Szijgyarto Eugene F. Schuster Hui Xiao Ben P. Haynes Ivana Sestak Jack Cuzick Laia Paré Elia Seguí Nuria Chic Aleix Prat Mitch Dowsett Maggie Chon U. Cheang
author_facet	Richard Buus Zsolt Szijgyarto Eugene F. Schuster Hui Xiao Ben P. Haynes Ivana Sestak Jack Cuzick Laia Paré Elia Seguí Nuria Chic Aleix Prat Mitch Dowsett Maggie Chon U. Cheang
author_sort	Richard Buus
title	Development and validation for research assessment of Oncotype DX® Breast Recurrence Score, EndoPredict® and Prosigna®
title_short	Development and validation for research assessment of Oncotype DX® Breast Recurrence Score, EndoPredict® and Prosigna®
title_full	Development and validation for research assessment of Oncotype DX® Breast Recurrence Score, EndoPredict® and Prosigna®
title_fullStr	Development and validation for research assessment of Oncotype DX® Breast Recurrence Score, EndoPredict® and Prosigna®
title_full_unstemmed	Development and validation for research assessment of Oncotype DX® Breast Recurrence Score, EndoPredict® and Prosigna®
title_sort	development and validation for research assessment of oncotype dx® breast recurrence score, endopredict® and prosigna®
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ab6604a1505e46ae8d5a30ae6561a42c
work_keys_str_mv	AT richardbuus developmentandvalidationforresearchassessmentofoncotypedxbreastrecurrencescoreendopredictandprosigna AT zsoltszijgyarto developmentandvalidationforresearchassessmentofoncotypedxbreastrecurrencescoreendopredictandprosigna AT eugenefschuster developmentandvalidationforresearchassessmentofoncotypedxbreastrecurrencescoreendopredictandprosigna AT huixiao developmentandvalidationforresearchassessmentofoncotypedxbreastrecurrencescoreendopredictandprosigna AT benphaynes developmentandvalidationforresearchassessmentofoncotypedxbreastrecurrencescoreendopredictandprosigna AT ivanasestak developmentandvalidationforresearchassessmentofoncotypedxbreastrecurrencescoreendopredictandprosigna AT jackcuzick developmentandvalidationforresearchassessmentofoncotypedxbreastrecurrencescoreendopredictandprosigna AT laiapare developmentandvalidationforresearchassessmentofoncotypedxbreastrecurrencescoreendopredictandprosigna AT eliasegui developmentandvalidationforresearchassessmentofoncotypedxbreastrecurrencescoreendopredictandprosigna AT nuriachic developmentandvalidationforresearchassessmentofoncotypedxbreastrecurrencescoreendopredictandprosigna AT aleixprat developmentandvalidationforresearchassessmentofoncotypedxbreastrecurrencescoreendopredictandprosigna AT mitchdowsett developmentandvalidationforresearchassessmentofoncotypedxbreastrecurrencescoreendopredictandprosigna AT maggiechonucheang developmentandvalidationforresearchassessmentofoncotypedxbreastrecurrencescoreendopredictandprosigna
_version_	1718391331043147776

Development and validation for research assessment of Oncotype DX® Breast Recurrence Score, EndoPredict® and Prosigna®

Ejemplares similares