Abstract P6-08-20: Prognostic significance of the interferon metagene in node-negative breast cancer depends on the molecular subtype

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, Jorg Rahnenfuhrer, 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.