Abstract
Background
Chemokines, cytokines in the immune microenvironment of tumors, may be associated
with patient outcome. We assessed the impact of CXCL13 and CXCL9 on disease-free (DFS)
and overall survival (OS), in an attempt to retrospectively evaluate both T and B
cell function in the microenvironment of primary tumors from patients with breast
cancer.
Materials and Methods
Formalin-fixed paraffin-embedded tissue blocks from patients with intermediate/high-risk,
early breast cancer, treated with sequential adjuvant epirubicin, paclitaxel, and
cyclophosphamide methotrexate fluorouracil within a randomized trial, were tested
for CXCL13 and CXCL9 messenger RNA expression; 557 patients with adequate tissue were
eligible for the analysis.
Results
CXCL13 was correlated with CXCL9 (rho = 0.52; P < .001). High-expressing CXL13 and CXCL9 tumors had higher Ki67 and tumor infiltrating
lymphocyte density (P-values < .001). High CXCL9 expression was an unfavorable prognosticator for OS among
all patients (hazard ratio [HR], 1.73; P = .021), whereas it showed favorable significance for both DFS and OS in patients
with triple negative disease (HR, 0.29; P = .027 and HR, 0.32; P = .045). High CXCL13 conferred longer DFS and OS among patients with luminal-human
epidermal growth factor receptor 2 disease (HR, 0.31; P = .013 and HR, 0.25; P = .005). Patients with low CXCL13 and high CXCL9 expression had shorter DFS and OS
compared with those with high expression of both chemokines (HR, 1.63; P = .006 and HR, 1.61; P = .016).
Conclusions
Both biomarkers were associated with poor prognosis characteristics and with tumor
infiltrating lymphocyte density. High CXCL9 conferred an improved prognosis in the
triple negative subtype, whereas high CXCL13 was associated with improved outcome
in the luminal-human epidermal growth factor receptor 2 subtype. Chemokines can be
associated with breast cancer subtype and outcome. These data should be evaluated
prospectively.
Keywords
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Article Info
Publication History
Published online: September 04, 2019
Accepted:
August 26,
2019
Received in revised form:
July 30,
2019
Received:
April 25,
2019
Identification
Copyright
© 2019 Elsevier Inc. All rights reserved.
