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

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.

• Authors: Max A A Ragusi, Tycho Bismeijer, Bas H M van der Velden, Claudette E Loo, Sander Canisius, Jelle Wesseling, Lodewyk F A Wessels, Sjoerd G Elias, Kenneth G A Gilhuijs
• Journal: Breast (Edinburgh, Scotland) (Breast) Vol. 60 Pg. 230-237 (Dec 2021) ISSN: 1532-3080 [Electronic] Netherlands
• PMID: 34763270 (Publication Type: Journal Article, Observational Study)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Receptor, ErbB-2
• Proteasome Endopeptidase Complex

Topics

• Breast Neoplasms (diagnostic imaging, genetics)
• Female
• Gene Expression
• Humans
• Magnetic Resonance Imaging
• Prognosis
• Prospective Studies
• Proteasome Endopeptidase Complex (genetics)
• Receptor, ErbB-2 (genetics)