Evaluation of the effect of CXCL13 mRNA expression in early breast cancer outcome: A confirmatory study.

e24286 Background: CXCL13 mRNA expression has been associated with subtype specific outcome in breast cancer and its prognostic markers. Methods: Early breast cancer patients with T1-4, N1-2, M0 were included in a prospective randomized trial (ACTRN12609001036202) and treated with anthracyclines and taxanes, concurrently or sequentially followed by cyclophosphamide/methotrexate/5 fluorouracil (CMF) from 2000 to 2005. Formalin fixed paraffin embedded tissue samples from the original surgery were tested for CXCL13 mRNA expression by qRT-PCR. All clinical and molecular parameters, including immunohistochemically defined breast cancer subtypes, were tested for their association with CXCL13 (high vs. low; predefined cut off of 32.9), as was its association with disease free (DFS) and overall survival (OS). The association with relapse/mortality rate was evaluated with Cox proportional hazards model. Results: A total of 557 patients were included. Of them, 50.8% had high-grade disease, 79.1% were ER/PgR positive and 22.8% were HER2-positive. CXCL13 was significantly associated with tumor size (p = 0.016), histological grade (p < 0.001), ER/PgR status (p = 0.034), HER2 status (p = 0.006) and breast cancer subtypes (p < 0.001). With a median follow-up of 124.2 months, 188 (33.8%) patients progressed and 149 (26.8%) died, with a 5-year DFS rate of 78.6% and OS of 88.2%. In multivariate analysis, high CXCL13 was marginally associated with improved DFS (p = 0.051) but not OS (p = 0.22) when adjusted for number of positive lymph nodes, tumor size, radiotherapy and subtypes. However, CXCL13 was found to have a significant impact on both DFS and OS in the luminal HER2 subgroup [DFS: HR 0.29, 95% CI 0.13-0.68, p = 0.004; HR 0.32, 95% CI 0.14-0.75, p = 0.009]. Of note high CXCL13 was significantly associated with the presence of tumor infiltrating lymphocytes(TILs) as indicated by its association with CD3, CD8 and FOXP3 (p-values < 0.001). Conclusions: High CXCL13 mRNA expression was significantly associated with poor prognostic parameters, but specifically in the luminal HER2 subgroup, it was found to have a significant positive impact on both DFS and OS, possibly due to its association with the tumor immune microenvironment and TILs.