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

Eur J Cancer. 2021 Jul:152:78-89. doi: 10.1016/j.ejca.2021.04.016. Epub 2021 Jun 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Breast / pathology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Disease-Free Survival
  • Female
  • Gene Expression Profiling
  • Genetic Testing / methods
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Observational Studies as Topic
  • Prognosis
  • Prospective Studies
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / analysis
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / analysis
  • Receptors, Progesterone / metabolism
  • Reproducibility of Results
  • Risk Assessment / methods
  • Risk Assessment / statistics & numerical data
  • Young Adult

Substances

  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2

Associated data

  • ClinicalTrials.gov/NCT02050750
  • ClinicalTrials.gov/NCT00310180