Abstract 3731: Elevated mRNA expression of CXCL13 predicts improved outcome in patients with high-risk early breast cancer: A possible molecular predictor of treatment benefit in the context of a Hellenic Cooperative Oncology Group trial

Abstract

Abstract Chemokines are important in cell migration and are therefore thought to play a key role in metastasis. Chemokine (C-X-C motif) ligand 13 (CXCL13) was recently found to be overexpressed in breast cancer and its overexpression is thought to be associated with poor outcome. The aim of the present study was to explore the prognostic significance of CXCL13 on disease-free survival (DFS) and overall survival (OS) in high-risk operable breast cancer enrolled in a randomized phase III trial. The association of CXCL13 with hormonal receptor and HER family expression at the m-RNA level, as well as with other clinicopathological characteristics of patients was also investigated. 595 high-risk breast cancer patients were treated in a two-arm trial (HE10/97) investigating postoperative dose-dense sequential chemotherapy with epirubicin (E) followed by CMF with or without paclitaxel (T). RNA was extracted from 312 formalin-fixed paraffin-embedded primary tumor tissue samples followed by kinetic one-step RT-PCR for assessment of mRNA expression of CXCL13, ER, PgR, and HER2. Values of CXCL13 and HER2 mRNA above the 75th percentile were considered high expression. CXCL13 expression was correlated with known clinicopathological parameters, such as HER2, ER and PgR by IHC, tumor grade, and nodal involvement. With a median follow up of 8 years the total number of events (disease relapses) was 109/312 (35%), and the total number of deaths 78/312 (25%). High CXCL13 mRNA expression was associated with improved DFS (log-rank, p=0.043). This remained unchanged when adjusted for treatment group (Wald, p=0.045). Furthermore, CXCL13 was found to be negatively correlated (p<0.001) with ER and PgR mRNA expression. Results of the Cox multivariate regression analysis revealed that, in the presence of treatment group, high CXCL13 mRNA expression was associated with a significantly decreased risk for relapse (HR=0.50, 95% CI: 0.31-0.82, p=0.006) and a significantly decreased risk for death (HR=0.56, 95% CI: 0.31-0.99, p=0.047). The number of ER/PgR IHC positive patients was significantly lower in the high expression group of CXCL13 compared to the low expression group (67.5% vs 81.5%, p=0.017). Finally, higher tumor grade was more likely to be present in the high expression group of CXCL13 than in the low expression group (69.2% vs 42.7%, p<0.001), as was HER2 mRNA overexpression (41.4% vs 26.5%, p=0.024). Furthermore, high expression of CXCL13 was associated with lower risk for relapse in HER2 mRNA overexpressing patients. High CXCL13 mRNA expression is associated with a significantly decreased risk for relapse and death in high-risk breast cancer patients treated with dose-dense sequential chemotherapy. This association appears to be more pronounced in HER2 overexpressing patients. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3731.