by 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
The Breast: FULL LENGTH ARTICLE| VOLUME
60, P230-237, DECEMBER 01, 2021
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.
