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

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.