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Contralateral parenchymal enhancement on MRI is associated with tumor proteasome pathway gene expression and overall survival of early ER+/HER2-breast cancer patients

Journal Article (2021)
Author(s)

Max A.A. Ragusi (Universiteit Utrecht, Antoni van Leeuwenhoek Ziekenhuis)

Tycho Bismeijer (Antoni van Leeuwenhoek Ziekenhuis)

Bas H.M. van der Velden (Universiteit Utrecht)

Claudette E. Loo (Antoni van Leeuwenhoek Ziekenhuis)

Sander Canisius (Antoni van Leeuwenhoek Ziekenhuis)

Jelle Wesseling (Antoni van Leeuwenhoek Ziekenhuis, Leiden University Medical Center)

Lodewyk F.A. Wessels (Antoni van Leeuwenhoek Ziekenhuis, TU Delft - Pattern Recognition and Bioinformatics)

Sjoerd G. Elias (Universiteit Utrecht)

Kenneth G.A. Gilhuijs (Universiteit Utrecht)

Research Group
Pattern Recognition and Bioinformatics
DOI related publication
https://doi.org/10.1016/j.breast.2021.11.002
More Info
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Publication Year
2021
Language
English
Research Group
Pattern Recognition and Bioinformatics
Volume number
60
Pages (from-to)
230-237
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Abstract

Purpose: To assess whether contralateral parenchymal enhancement (CPE) on MRI is associated with gene expression pathways in ER+/HER2-breast cancer, and if so, whether such pathways are related to survival. Methods: Preoperative breast MRIs were analyzed of early ER+/HER2-breast cancer patients eligible for breast-conserving surgery included in a prospective observational cohort study (MARGINS). The contralateral parenchyma was segmented and CPE was calculated as the average of the top-10% delayed enhancement. Total tumor RNA sequencing was performed and gene set enrichment analysis was used to reveal gene expression pathways associated with CPE (N = 226) and related to overall survival (OS) and invasive disease-free survival (IDFS) in multivariable survival analysis. The latter was also done for the METABRIC cohort (N = 1355). Results: CPE was most strongly correlated with proteasome pathways (normalized enrichment statistic = 2.04, false discovery rate =.11). Patients with high CPE showed lower tumor proteasome gene expression. Proteasome gene expression had a hazard ratio (HR) of 1.40 (95% CI = 0.89, 2.16; P =.143) for OS in the MARGINS cohort and 1.53 (95% CI = 1.08, 2.14; P =.017) for IDFS, in METABRIC proteasome gene expression had an HR of 1.09 (95% CI = 1.01, 1.18; P =.020) for OS and 1.10 (95% CI = 1.02, 1.18; P =.012) for IDFS. Conclusion: CPE was negatively correlated with tumor proteasome gene expression in early ER+/HER2-breast cancer patients. Low tumor proteasome gene expression was associated with improved survival in the METABRIC data.