Prognostic significance of the chemokine CXCL13 in node-negative breast cancer.

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<0.0001). Prognostic significance was most pronounced in the HER2+ positive molecular subtype (HR 0.72, 95% CI 0.59-0.87, P=0.0009) as compared to ER+/HER2- (HR 0.86, 95% CI 0.76-0.98, P=0.0024) and ER-/HER2- (HR 0.85, 95% CI 0.75-0.98), P=0.02) carcinomas of the breast. CXCL13 showed independent prognostic significance (HR 0.81, 95% CI 0.7336 0.8982, P=0.0001) in multivariate analysis. In addition to CXCL13, only histological grade of differentiation (HR 2.20, 95% CI 1.41-3.42, P=0.0005) and tumor size (HR 1.72, 95% CI 1.13-2.61, P=0.012), but neither age nor HER2 status nor hormone receptor status retained an independent prognostic association with MFS. Conclusions: The chemokine CXCL13 has independent prognostic significance in node-negative breast cancer. Higher expression of CXCL13 is associated with improved outcome.

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Prediction of late metastasis in node-negative breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.10551 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 10551-10551

Author(s):

Marcus Schmidt ◽

Birte Hellwig ◽

Mathias Gehrmann ◽

Heinz Koelbl ◽

Daniel Boehm ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Cox Regression ◽

Prognostic Significance ◽

Gene Array ◽

Breast Cancer Patients ◽

Node Negative ◽

Node Negative Breast Cancer ◽

Increased Risk ◽

Late Metastasis

10551 Background: Prediction of late metastasis is of clinical relevance in breast cancer. However, systematic genome-wide studies to identify genes associated with increased risk of metastasis 5 or more years after surgery are scarce. Methods: We examined the natural course of disease in three previously published cohorts (Mainz, Rotterdam, Transbig) including 766 node-negative breast cancer patients with gene array data who did not receive systemic chemotherapy in the adjuvant setting. We established a Cox regression based method adjusted for multiple testing that identified genes predicting late metastasis (5 or more years after surgery). Only those genes were accepted that showed similar results in all three cohorts. Metastasis-free survival (MFS) was analyzed with univariate and multivariate Cox regression. Results: We identified 9 genes [ABCC5 (Hazard Ratio (HR) 2.19, p=0.003), EDDM3B (HR 3.58, p=0.044), RAD23B (HR 0.37, p<0.001), XYLT2 (HR 2.19, p=0.027), DDX18 (HR 0.35, p=0.006), GPBP1L1 (HR 0.20, p=0.018), UBB (HR 9.73, p=0.025), RPS24 (HR 0.20, p=0.050), GPC1 (HR 2.36, p=0.013)] predicting late metastasis. These genes retained their independent prognostic significance after adjustment for established clinical factors (age, tumor size, grade, hormone receptor status, HER2) and biological motives like estrogen receptor, proliferation, B or T cells. These late-type genes are largely associated with resistance to hypoxia, apoptosis and DNA damage, suggesting that they might contribute to persistence of disseminated tumor cells. Conclusions: Genes associated with late metastasis offer a perspective to identify breast cancer patients suitable for additional and prolonged therapies.

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