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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

Clinical significance of the nuclear receptor co-regulator DC-SCRIPT in breast cancer: an independent retrospective

Anieta M Sieuwerts¹, Marleen Ansems, Maxime P Look

¹Department of Medical Oncology, Josephine Nefkens Institute and Cancer Genomics Centre, Erasmus Medical Center, Rotterdam, GE, The Netherlands. a.sieuwerts@erasmusmc.nl

Breast Cancer Research : BCR

|December 3, 2010

Abstract

Introduction:

In this study we aimed to validate the prognostic value of DC-SCRIPT mRNA expression in a large independent breast cancer cohort. In addition, since DC-SCRIPT is a transcriptional co-regulator of nuclear receptors, we explored its prognostic value in relation to estrogen-receptor-α (ESR1) and -β (ESR2) and evaluated its predictive value for response to tamoxifen treatment.

Methods:

DC-SCRIPT mRNA levels were measured by real-time PCR in 1,505 primary invasive breast cancers and associated with outcome (disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS)) using univariate and multivariable Cox regression analysis. Logistic and Cox regressions were used to associate DC-SCRIPT levels with clinical benefit and progression-free survival (PFS) for 296 patients treated with first-line systemic tamoxifen for advanced disease.

Results:

In univariate and multivariable analysis higher DC-SCRIPT levels were associated with a favorable outcome for both the entire cohort and patients with lymph node-negative (LNN) disease that did not receive adjuvant therapy (DFS, MFS and OS; all, P < 0.001). This association was most pronounced in small (pT1) tumors, in ESR1-positive tumors and in tumors with low ESR2 expression. For first-line endocrine therapy for advanced disease no predictive association was seen with clinical benefit or PFS.

Conclusions:

This study provides a higher level of evidence that DC-SCRIPT is indeed an independent, pure prognostic, factor for primary breast cancer and shows that DC-SCRIPT mRNA expression is most informative for either ESR1-positive and/or ESR2-low pT1 tumors.

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