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Several studies suggest a link between circadian rhythm disturbances and tumorigenesis. However, the association between circadian clock genes and prognosis in breast cancer has not been systematically studied. Therefore, we examined the expression of 17 clock components in tumors from 766 node-negative breast cancer patients that were untreated in both neoadjuvant and adjuvant settings. In addition, their association with metastasis-free survival (MFS) and correlation to clinicopathological parameters were investigated. Aiming to estimate functionality of the clockwork, we studied clock gene expression relationships by correlation analysis. Higher expression of several clock genes (e.g., CLOCK, PER1, PER2, PER3, CRY2, NPAS2 and RORC) was found to be associated with longer MFS in univariate Cox regression analyses (HR

Background: Interferons are crucial for adaptive immunity and play an important role as central coordinators of tumor-immune system interactions. We examined the subtype specific prognostic significance of an interferon (IFN) metagene in node-negative breast cancer. Methods: Using microarray based gene-expression data, we identified co-regulated genes related to biological processes. After hierarchical clustering, we defined an interferon (IFN) metagene which was composed of 36 interferon-stimulated genes. The subtype specific prognostic role of the IFN metagene was analysed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n=824). A meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance of the IFN metagene for metastasis-free survival (MFS) was examined in different molecular subtypes: luminal A (ER+/HER2-/aurora kinase A [AURKA]low, luminal B (ER+/HER2-/AURKAhigh), basal-like (ER-/HER2-), and HER2+. Results: Prognostic significance of the IFN metagene was restricted to the HER2+ positive molecular subtype (HR 0.50, 95% CI 0.28-0.88, P=0.0056). Prognostic effects were not seen in luminal A (HR 1.00, 95% CI 0.65-1.53, P=0.8819), luminal B (HR 1.00, 95% CI 0.76-1.32, P=0.9770) or basal-like (HR 0.87, 95% CI 0.66-1.15, P=0.3282) carcinomas of the breast. Conclusions: The prognostic significance of the interferon metagene in node-negative breast cancer is subtype specific and confined to the HER2+ molecular subtype. A higher expression of the IFN metagene is associated with improved outcome in HER2+ breast cancer. Citation Format: Marcus Schmidt, Leonie van de Sandt, Karolina Edlund, Isabel Sicking, Marco Battista, Anne-Sophie Heimes, Antje Lebrecht, Gerald Hoffmann, Mathias Gehrmann, Jörg Rahnenführer, Jan G Hengstler. Prognostic significance of the interferon metagene in node-negative breast cancer depends on the molecular subtype [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-20.

615 Background: The chemokine CXCL13 is chemotactic for B cells. We examined the prognostic significance of CXCL13 mRNA expression in node-negative breast cancer. Methods: Microarray based gene-expression data for CXCL13 (205242_at) were analysed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n=824). A meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance of CXCL13 on metastasis-free survival (MFS) was examined in the whole cohort and in different molecular subtypes (ER+/HER2-, ER-/HER2-, HER2+). Independent prognostic relevance was analysed using multivariate Cox regression. Results: Higher RNA expression of CXCL13 was related to better MFS in a meta-analysis of the whole cohort (HR 0.88, 95% CI 0.83-0.94, P

552 Background: Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase playing an important role as a key mediator for signal transduction. We examined the subtype specific prognostic signifi...

620 Background: The transcription factor IRF4 (interferon regulating factor 4) regulates immunoglobulin class switch recombination as well as plasma cell differentiation. We examined the prognostic significance of IRF4 mRNA expression in node-negative breast cancer. Methods: Microarray based gene-expression data for IRF4 (204562_at) were analysed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n=824). A meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance of IRF4 on metastasis-free survival (MFS) was examined in the whole cohort and in different molecular subtypes: luminal A (ER+/HER2-/aurora kinase A [AURKA]low, luminal B (ER+/HER2-/AURKAhigh), basal-like (ER-/HER2-), HER2+. Independent prognostic relevance was analysed using multivariate Cox regression. Results: Higher RNA expression of IRF4 was related to better MFS in a meta-analysis of the whole...