EarlyR: A Robust Gene Expression Signature for Predicting Outcomes of Estrogen Receptor-Positive Breast Cancer.

Autor: Buechler SA; Department of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN., Gökmen-Polar Y; Department of Pathology, Indiana University School of Medicine, Indianapolis, IN., Badve SS; Department of Pathology, Indiana University School of Medicine, Indianapolis, IN; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN. Electronic address: sbadve@iupui.edu.
Jazyk: angličtina
Zdroj: Clinical breast cancer [Clin Breast Cancer] 2019 Feb; Vol. 19 (1), pp. 17-26.e8. Date of Electronic Publication: 2018 Jul 17.
DOI: 10.1016/j.clbc.2018.07.011
Abstrakt: Introduction: Early stage estrogen receptor (ER)-positive breast cancer may be treated with chemotherapy in addition to hormone therapy. Currently available molecular signatures assess the risk of recurrence and the benefit of chemotherapy; however, these tests may have large intermediate risk groups, limiting their usefulness.
Methods: The EarlyR prognostic score was developed using integrative analysis of microarray data sets and formalin-fixed, paraffin-embedded-based quantitative real-time PCR assay and validated in Affymetrix data sets and METABRIC cohort using Cox proportional hazards models and Kaplan-Meier survival analysis. Concordance index was used to measure the probability of prognostic score agreement with outcome.
Results: The EarlyR score and categorical risk strata (EarlyR-Low, EarlyR-Int, EarlyR-High) derived from expression of ESPL1, MKI67, SPAG5, PLK1 and PGR was prognostic of 8-year distant recurrence-free interval in Affymetrix (categorical P = 3.5 × 10 -14 ; continuous P = 8.8 × 10 -15 ) and METABRIC (categorical P < 2.2 × 10 -16 ; continuous P < 10 -16 ) data sets of ER + breast cancer. Similar results were observed for the breast cancer-free interval end point. At most 13% of patients were intermediate risk and at least 66% patients were low risk in both ER + cohorts. The EarlyR score was significantly prognostic (distant recurrence-free interval; P < .001) in both lymph node-negative and lymph node-positive patients and was independent from clinical factors. EarlyR and surrogates of current molecular signatures were comparable in prognostic significance by concordance index.
Conclusion: The 5-gene EarlyR score is a robust prognostic assay that identified significantly fewer patients as intermediate risk and more as low risk than currently available assays. Further validation of the assay in clinical trial-derived cohorts is ongoing.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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