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, 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
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 = 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.
Trial registration: ClinicalTrials.gov NCT02050750 NCT00310180.
Keywords: Breast cancer; ER+/HER2-; Prognostic biomarker; Recurrence score.
Conflict of interest statement
Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.P.B. and W.M.G. report a patent issued and licensed to OncoMark Ltd., with all rights transferred to The Provost, Fellows, Foundation Scholars and the other members of the Board, the College of the Holy and Undivided Trinity of Queen Elizabeth near Dublin, and University College Dublin, National University of Ireland, Dublin. D.O'L. and W.M.G. report being employees and shareholders of OncoMark Ltd. J.C., S.B., C.-J.A.W., T.L., P.D., B.F. and C.L.-R. report being employees of OncoMark Ltd. D.P.O'C. reports receiving a travel bursary to part support attendance at ASCO 2019 from OncoMark. All the remaining authors have declared no conflicts of interest.
Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
Source: PubMed