Prognostic value of the 6-gene OncoMasTR test in hormone receptor–positive HER2-negative early-stage breast cancer: Comparative analysis with standard clinicopathological factors

Seodhna M. Lynch; Niamh M. Russell; Stephen Barron; Chan-ju A. Wang; Tony Loughman; Peter Dynoodt; Bozena Fender; Cesar Lopez-ruiz; Anthony O'grady; Katherine M. Sheehan; Joanna Fay; Verena Amberger-murphy; Anurati Saha; Rut Klinger; Claudia A. Gonzalez; Nebras Al-attar; Arman Rahman; Desmond O'leary; Fiona T. Lanigan; Adrian P. Bracken; John Crown; Catherine M. Kelly; Darran P. O'connor; William M. Gallagher

doi:10.1016/j.ejca.2021.04.016

Prognostic value of the 6-gene OncoMasTR test in hormone receptor–positive HER2-negative early-stage breast cancer: Comparative analysis with standard clinicopathological factors

Seodhna M. Lynch, Niamh M. Russell, Stephen Barron, Chan-ju A. Wang, Tony Loughman, Peter Dynoodt, Bozena Fender, Cesar Lopez-ruiz, Anthony O'grady, Katherine M. Sheehan, Joanna Fay, Verena Amberger-murphy, Anurati Saha, Rut Klinger, Claudia A. Gonzalez, Nebras Al-attar, Arman Rahman, Desmond O'leary, Fiona T. Lanigan, Adrian P. BrackenJohn Crown, Catherine M. Kelly, Darran P. O'connor, William M. Gallagher

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Abstract

Aim: The aim of the study was to assess the prognostic performance of a 6-gene
molecular score (OncoMasTR Molecular Score [OMm]) and a composite risk score (OncoMasTR Risk Score [OM]) and to conduct a within-patient comparison against four routinely used molecular and clinicopathological risk assessment tools: Oncotype DX Recurrence Score, Ki67, Nottingham Prognostic Index and Clinical Risk Category, based on the modified Adjuvant! Online definition and three risk factors: patient age, tumour size and grade.
Methods: Biospecimens and clinicopathological information for 404 Irish women also previously enrolled in the Trial Assigning Individualized Options for Treatment [Rx] were provided by 11 participating hospitals, as the primary objective of an independent translational study. Gene expression measured via RT-qPCR was used to calculate OMm and OM. The prognostic value for distant recurrence-free survival (DRFS) and invasive disease-free survival (IDFS) was assessed using Cox proportional hazards models and Kaplan-Meier analysis.
All statistical tests were two-sided ones.
Results: OMm and OM (both with likelihood ratio statistic [LRS] P < 0.001; C
indexes Z 0.84 and 0.85, respectively) were more prognostic for DRFS and provided significant additional prognostic information to all other assessment tools/factors assessed (all LRS P 0.002). In addition, the OM correctly classified more patients with distant recurrences (DRs) into the high-risk category than other risk classification tools. Similar results were observed for IDFS.
Discussion: Both OncoMasTR scores were significantly prognostic for DRFS and IDFS and provided additional prognostic information to the molecular and clinicopathological risk factors/tools assessed. OM was also the most accurate risk classification tool for identifying DR. A concise 6-gene signature with superior risk stratification was shown to increase prognosis reliability, which may help clinicians optimise treatment decisions.

Original language	English
Pages (from-to)	78-89
Number of pages	12
Journal	European Journal of Cancer
Volume	152
Early online date	2 Jun 2021
DOIs	https://doi.org/10.1016/j.ejca.2021.04.016
Publication status	Published (in print/issue) - 1 Jul 2021

Bibliographical note

The work was supported by European Union's Horizon 2020 research and innovation programme awarded to OncoMark under grant agreement number 698630. W.M.G. was supported by the Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT (grant number: CCRC13GAL), as well as Science Foundation Ireland (SFI) under the Investigator Programme OPTi-PREDICT (grant number: 15/IA/3104) and the Strategic Research Programme Precision Oncology Ireland (grant number: 18/SPP/3522). D.P.O'C. was also supported by SFI (grant number: 12TIDAB2436 and 18/SPP/3522) and received a SFI Career Development Award (grant number: 15/CDA/3438). The funding sources had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript and decision to submit the manuscript for publication.

Keywords

Breast cancer
ER+/HER2-
Prognostic biomarker
Recurrence score

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

Lynch, S. M., Russell, N. M., Barron, S., Wang, C. A., Loughman, T., Dynoodt, P., Fender, B., Lopez-ruiz, C., O'grady, A., Sheehan, K. M., Fay, J., Amberger-murphy, V., Saha, A., Klinger, R., Gonzalez, C. A., Al-attar, N., Rahman, A., O'leary, D., Lanigan, F. T., ... Gallagher, W. M. (2021). Prognostic value of the 6-gene OncoMasTR test in hormone receptor–positive HER2-negative early-stage breast cancer: Comparative analysis with standard clinicopathological factors. European Journal of Cancer, 152, 78-89. Advance online publication. https://doi.org/10.1016/j.ejca.2021.04.016

@article{1adbd70c07ab4740bfa40b670698d131,

title = "Prognostic value of the 6-gene OncoMasTR test in hormone receptor–positive HER2-negative early-stage breast cancer: Comparative analysis with standard clinicopathological factors",

abstract = "Aim: The aim of the study was to assess the prognostic performance of a 6-genemolecular score (OncoMasTR Molecular Score [OMm]) and a composite risk score (OncoMasTR Risk Score [OM]) and to conduct a within-patient comparison against four routinely used molecular and clinicopathological risk assessment tools: Oncotype DX Recurrence Score, Ki67, Nottingham Prognostic Index and Clinical Risk Category, based on the modified Adjuvant! Online definition and three risk factors: patient age, tumour size and grade.Methods: Biospecimens and clinicopathological information for 404 Irish women also previously enrolled in the Trial Assigning Individualized Options for Treatment [Rx] were provided by 11 participating hospitals, as the primary objective of an independent translational study. Gene expression measured via RT-qPCR was used to calculate OMm and OM. The prognostic value for distant recurrence-free survival (DRFS) and invasive disease-free survival (IDFS) was assessed using Cox proportional hazards models and Kaplan-Meier analysis.All statistical tests were two-sided ones.Results: OMm and OM (both with likelihood ratio statistic [LRS] P < 0.001; Cindexes Z 0.84 and 0.85, respectively) were more prognostic for DRFS and provided significant additional prognostic information to all other assessment tools/factors assessed (all LRS P 0.002). In addition, the OM correctly classified more patients with distant recurrences (DRs) into the high-risk category than other risk classification tools. Similar results were observed for IDFS.Discussion: Both OncoMasTR scores were significantly prognostic for DRFS and IDFS and provided additional prognostic information to the molecular and clinicopathological risk factors/tools assessed. OM was also the most accurate risk classification tool for identifying DR. A concise 6-gene signature with superior risk stratification was shown to increase prognosis reliability, which may help clinicians optimise treatment decisions.",

keywords = "Breast cancer, ER+/HER2-, Prognostic biomarker, Recurrence score",

author = "Lynch, {Seodhna M.} and Russell, {Niamh M.} and Stephen Barron and Wang, {Chan-ju A.} and Tony Loughman and Peter Dynoodt and Bozena Fender and Cesar Lopez-ruiz and Anthony O'grady and Sheehan, {Katherine M.} and Joanna Fay and Verena Amberger-murphy and Anurati Saha and Rut Klinger and Gonzalez, {Claudia A.} and Nebras Al-attar and Arman Rahman and Desmond O'leary and Lanigan, {Fiona T.} and Bracken, {Adrian P.} and John Crown and Kelly, {Catherine M.} and O'connor, {Darran P.} and Gallagher, {William M.}",

note = "The work was supported by European Union's Horizon 2020 research and innovation programme awarded to OncoMark under grant agreement number 698630. W.M.G. was supported by the Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT (grant number: CCRC13GAL), as well as Science Foundation Ireland (SFI) under the Investigator Programme OPTi-PREDICT (grant number: 15/IA/3104) and the Strategic Research Programme Precision Oncology Ireland (grant number: 18/SPP/3522). D.P.O'C. was also supported by SFI (grant number: 12TIDAB2436 and 18/SPP/3522) and received a SFI Career Development Award (grant number: 15/CDA/3438). The funding sources had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript and decision to submit the manuscript for publication.",

year = "2021",

month = jul,

day = "1",

doi = "10.1016/j.ejca.2021.04.016",

language = "English",

volume = "152",

pages = "78--89",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier",

}

Lynch, SM, Russell, NM, Barron, S, Wang, CA, Loughman, T, Dynoodt, P, Fender, B, Lopez-ruiz, C, O'grady, A, Sheehan, KM, Fay, J, Amberger-murphy, V, Saha, A, Klinger, R, Gonzalez, CA, Al-attar, N, Rahman, A, O'leary, D, Lanigan, FT, Bracken, AP, Crown, J, Kelly, CM, O'connor, DP & Gallagher, WM 2021, 'Prognostic value of the 6-gene OncoMasTR test in hormone receptor–positive HER2-negative early-stage breast cancer: Comparative analysis with standard clinicopathological factors', European Journal of Cancer, vol. 152, pp. 78-89. https://doi.org/10.1016/j.ejca.2021.04.016

Prognostic value of the 6-gene OncoMasTR test in hormone receptor–positive HER2-negative early-stage breast cancer: Comparative analysis with standard clinicopathological factors. / Lynch, Seodhna M.; Russell, Niamh M.; Barron, Stephen et al.
In: European Journal of Cancer, Vol. 152, 01.07.2021, p. 78-89.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Prognostic value of the 6-gene OncoMasTR test in hormone receptor–positive HER2-negative early-stage breast cancer: Comparative analysis with standard clinicopathological factors

AU - Lynch, Seodhna M.

AU - Russell, Niamh M.

AU - Barron, Stephen

AU - Wang, Chan-ju A.

AU - Loughman, Tony

AU - Dynoodt, Peter

AU - Fender, Bozena

AU - Lopez-ruiz, Cesar

AU - O'grady, Anthony

AU - Sheehan, Katherine M.

AU - Fay, Joanna

AU - Amberger-murphy, Verena

AU - Saha, Anurati

AU - Klinger, Rut

AU - Gonzalez, Claudia A.

AU - Al-attar, Nebras

AU - Rahman, Arman

AU - O'leary, Desmond

AU - Lanigan, Fiona T.

AU - Bracken, Adrian P.

AU - Crown, John

AU - Kelly, Catherine M.

AU - O'connor, Darran P.

AU - Gallagher, William M.

N1 - The work was supported by European Union's Horizon 2020 research and innovation programme awarded to OncoMark under grant agreement number 698630. W.M.G. was supported by the Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT (grant number: CCRC13GAL), as well as Science Foundation Ireland (SFI) under the Investigator Programme OPTi-PREDICT (grant number: 15/IA/3104) and the Strategic Research Programme Precision Oncology Ireland (grant number: 18/SPP/3522). D.P.O'C. was also supported by SFI (grant number: 12TIDAB2436 and 18/SPP/3522) and received a SFI Career Development Award (grant number: 15/CDA/3438). The funding sources had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript and decision to submit the manuscript for publication.

PY - 2021/7/1

Y1 - 2021/7/1

N2 - Aim: The aim of the study was to assess the prognostic performance of a 6-genemolecular score (OncoMasTR Molecular Score [OMm]) and a composite risk score (OncoMasTR Risk Score [OM]) and to conduct a within-patient comparison against four routinely used molecular and clinicopathological risk assessment tools: Oncotype DX Recurrence Score, Ki67, Nottingham Prognostic Index and Clinical Risk Category, based on the modified Adjuvant! Online definition and three risk factors: patient age, tumour size and grade.Methods: Biospecimens and clinicopathological information for 404 Irish women also previously enrolled in the Trial Assigning Individualized Options for Treatment [Rx] were provided by 11 participating hospitals, as the primary objective of an independent translational study. Gene expression measured via RT-qPCR was used to calculate OMm and OM. The prognostic value for distant recurrence-free survival (DRFS) and invasive disease-free survival (IDFS) was assessed using Cox proportional hazards models and Kaplan-Meier analysis.All statistical tests were two-sided ones.Results: OMm and OM (both with likelihood ratio statistic [LRS] P < 0.001; Cindexes Z 0.84 and 0.85, respectively) were more prognostic for DRFS and provided significant additional prognostic information to all other assessment tools/factors assessed (all LRS P 0.002). In addition, the OM correctly classified more patients with distant recurrences (DRs) into the high-risk category than other risk classification tools. Similar results were observed for IDFS.Discussion: Both OncoMasTR scores were significantly prognostic for DRFS and IDFS and provided additional prognostic information to the molecular and clinicopathological risk factors/tools assessed. OM was also the most accurate risk classification tool for identifying DR. A concise 6-gene signature with superior risk stratification was shown to increase prognosis reliability, which may help clinicians optimise treatment decisions.

AB - Aim: The aim of the study was to assess the prognostic performance of a 6-genemolecular score (OncoMasTR Molecular Score [OMm]) and a composite risk score (OncoMasTR Risk Score [OM]) and to conduct a within-patient comparison against four routinely used molecular and clinicopathological risk assessment tools: Oncotype DX Recurrence Score, Ki67, Nottingham Prognostic Index and Clinical Risk Category, based on the modified Adjuvant! Online definition and three risk factors: patient age, tumour size and grade.Methods: Biospecimens and clinicopathological information for 404 Irish women also previously enrolled in the Trial Assigning Individualized Options for Treatment [Rx] were provided by 11 participating hospitals, as the primary objective of an independent translational study. Gene expression measured via RT-qPCR was used to calculate OMm and OM. The prognostic value for distant recurrence-free survival (DRFS) and invasive disease-free survival (IDFS) was assessed using Cox proportional hazards models and Kaplan-Meier analysis.All statistical tests were two-sided ones.Results: OMm and OM (both with likelihood ratio statistic [LRS] P < 0.001; Cindexes Z 0.84 and 0.85, respectively) were more prognostic for DRFS and provided significant additional prognostic information to all other assessment tools/factors assessed (all LRS P 0.002). In addition, the OM correctly classified more patients with distant recurrences (DRs) into the high-risk category than other risk classification tools. Similar results were observed for IDFS.Discussion: Both OncoMasTR scores were significantly prognostic for DRFS and IDFS and provided additional prognostic information to the molecular and clinicopathological risk factors/tools assessed. OM was also the most accurate risk classification tool for identifying DR. A concise 6-gene signature with superior risk stratification was shown to increase prognosis reliability, which may help clinicians optimise treatment decisions.

KW - Breast cancer

KW - ER+/HER2-

KW - Prognostic biomarker

KW - Recurrence score

U2 - 10.1016/j.ejca.2021.04.016

DO - 10.1016/j.ejca.2021.04.016

M3 - Article

C2 - 34090143

SN - 0959-8049

VL - 152

SP - 78

EP - 89

JO - European Journal of Cancer

JF - European Journal of Cancer

ER -

Prognostic value of the 6-gene OncoMasTR test in hormone receptor–positive HER2-negative early-stage breast cancer: Comparative analysis with standard clinicopathological factors

Abstract

Bibliographical note

Keywords

UN SDGs

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