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.
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 |
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Pages (from-to) | 78-89 |
Number of pages | 12 |
Journal | European Journal of Cancer |
Volume | 152 |
Early online date | 2 Jun 2021 |
DOIs | |
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