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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.

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