Dataset Information

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.

SUBMITTER: Ragusi MAA

PROVIDER: S-EPMC8591464 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Ragusi Max A A MAA Bismeijer Tycho T van der Velden Bas H M BHM Loo Claudette E CE Canisius Sander S Wesseling Jelle J Wessels Lodewyk F A LFA Elias Sjoerd G SG Gilhuijs Kenneth G A KGA

Breast (Edinburgh, Scotland) 20211102

<h4>Purpose</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 34763270

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Project description:BackgroundBackground parenchymal enhancement (BPE) on dynamic contrast-enhanced (DCE)-MRI has been associated with breast cancer risk, both based on qualitative and quantitative assessments.PurposeTo investigate whether BPE of the contralateral breast on preoperative DCE-MRI is associated with therapy outcome in ER-positive, HER2-negative, node-negative invasive breast cancer.Study typeRetrospective.PopulationIn all, 289 patients with unilateral ER-positive, HER2-negative, node-negative breast cancer larger than 5 mm.Field strength/sequence3T, T1 -weighted DCE sequence.AssessmentBPE of the contralateral breast was assessed qualitatively by two dedicated radiologists and quantitatively (using region-of-interest and automatic breast segmentation).Statistical testsCox regression analysis was used to determine associations with recurrence-free survival (RFS) and distant metastasis-free survival (DFS). Interobserver variability for parenchymal enhancement was assessed using kappa statistics and intraclass correlation coefficient (ICC).ResultsThe median follow-up time was 75.8 months. Multivariate analysis showed receipt of total mastectomy (hazard ratio [HR]: 5.497) and high Ki-67 expression level (HR: 5.956) were independent factors associated with worse RFS (P < 0.05). Only a high Ki-67 expression level was associated with worse DFS (HR: 3.571, P = 0.045). BPE assessments were not associated with outcome (RFS [qualitative BPE: P = 0.75, 0.92 for readers 1 and 2; quantitative BPE: P = 0.38-0.99], DFS, [qualitative BPE: P = 0.41, 0.16 for readers 1 and 2; quantitative BPE: P = 0.68-0.99]). For interobserver variability, there was good agreement between qualitative (κ = 0.700) and good to perfect agreement for most quantitative parameters of BPE.Data conclusionContralateral BPE showed no association with survival outcome in patients with ER-positive, HER2-negative, node-negative invasive breast cancer. A high Ki-67 expression level was associated with both worse recurrence-free and distant metastasis-free survival.Level of evidence3 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;48:1678-1689.

Project description:ObjectivesTo investigate whether contralateral parenchymal enhancement (CPE) on MRI during neoadjuvant endocrine therapy (NET) is associated with the preoperative endocrine prognostic index (PEPI) of ER+/HER2- breast cancer.MethodsThis retrospective observational cohort study included 40 unilateral ER+/HER2- breast cancer patients treated with NET. Patients received NET for 6 to 9 months with MRI response monitoring after 3 and/or 6 months. PEPI was used as endpoint. PEPI is based on surgery-derived pathology (pT- and pN-stage, Ki67, and ER-status) and stratifies patients in three groups with distinct prognoses. Mixed effects and ROC analysis were performed to investigate whether CPE was associated with PEPI and to assess discriminatory ability.ResultsThe median patient age was 61 (interquartile interval: 52, 69). Twelve patients had PEPI-1 (good prognosis), 15 PEPI-2 (intermediate), and 13 PEPI-3 (poor). High pretreatment CPE was associated with PEPI-3: pretreatment CPE was 39.4% higher on average (95% CI = 1.3, 91.9%; p = .047) compared with PEPI-1. CPE decreased after 3 months in PEPI-2 and PEPI-3. The average reduction was 24.4% (95% CI = 2.6, 41.3%; p = .032) in PEPI-2 and 29.2% (95% CI = 7.8, 45.6%; p = .011) in PEPI-3 compared with baseline. Change in CPE was predictive of PEPI-1 vs PEPI-2+3 (AUC = 0.77; 95% CI = 0.57, 0.96).ConclusionsCPE during NET is associated with PEPI-group in ER+/HER2- breast cancer: a high pretreatment CPE and a decrease in CPE during NET were associated with a poor prognosis after NET on the basis of PEPI.Key points• Change in contralateral breast parenchymal enhancement on MRI during neoadjuvant endocrine therapy distinguished between patients with a good and intermediate/poor prognosis at final pathology. • Patients with a poor prognosis at final pathology showed higher baseline parenchymal enhancement on average compared to patients with a good prognosis. • Patients with an intermediate/poor prognosis at final pathology showed a higher average reduction in parenchymal enhancement after 3 months of neoadjuvant endocrine therapy.

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Dataset Information

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

Purpose

Methods

Results

Conclusion

Publications

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

Similar Datasets

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