Improved outcome of high-risk early HER2 positive breast cancer with high CXCL13-CXCR5 messenger RNA expression

Autor: Razi, E. D., Kalogeras, K. T., Kotoula, V., Eleftheraki, A. G., Nikitas, N., Kronenwett, R., Timotheadou, E., Christodoulou, C., Pectasides, Dimitrios, Gogas, H., Wirtz, R. M., Makatsoris, T., Bafaloukos, Dimitrios, Aravantinos, Gerasimos, Televantou, D., Pavlidis, Nicholas, Fountzilas, George
Přispěvatelé: Pavlidis, Nicholas [0000-0002-2195-9961], Aravantinos, Gerasimos [0000-0002-2106-1713], Kotoula, V. [0000-0002-8657-9732]
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Cancer Research
Human epidermal growth factor receptor 2
Receptor
ErbB-2
Messenger rna
Estrogen receptor
Cancer staging
CXCR5
Quantitative assay
Metastasis
Progesterone receptor
Cancer risk
Multiple cycle treatment
Breast cancer
Antineoplastic Combined Chemotherapy Protocols
Medicine
Multicenter Studies as Topic
Overall survival
Receptor
Disease free survival
Cxcl13
Cxcl13 chemokine
Cxcl12
Protein motif
Cxcr5
Randomized Controlled Trials as Topic
Chemokine receptor cxcr5
Chemokine receptor cxcr4
Middle Aged
Prognosis
Up-Regulation
Gene Expression Regulation
Neoplastic
Treatment Outcome
Oncology
Hormone receptor
Paraffin
Granulocyte colony stimulating factor
Reverse transcription polymerase chain reaction
Female
Cancer chemotherapy
Fluorouracil
Chemokines
Cancer tissue
Human
Receptors
CXCR5
Risk
Adult
Paclitaxel
Tissue fixation
Hazard ratio
Tumor associated leukocyte
Breast Neoplasms
Major clinical study
Article
Epidermal growth factor receptor 2
Young Adult
Formaldehyde
Biomarkers
Tumor
Tau protein
Humans
RNA
Messenger
Human tissue
Cyclophosphamide
Retrospective Studies
Aged
Epirubicin
Messenger RNA
Cancer prognosis
Dose-Response Relationship
Drug
business.industry
Carcinoma
medicine.disease
Chemokine CXCL13
Cancer survival
Rna extraction
Outcome assessment
Methotrexate
Multivariate analysis
Cancer research
Cancer adjuvant therapy
Cancer patient
Protein expression
business
Controlled study
Zdroj: Clinical Breast Cancer
Popis: The CXCL13-CXCR5 is a chemokine axis that is activated in some breast cancers. A total of 321 tissue blocks from a group of patients who received adjuvant, dose-dense chemotherapy for high-risk early breast cancer were examined. Activation of this axis was found to be associated with determinants of poor prognosis but also with improved outcome in the human epidermal growth factor receptor 2 overexpressing subpopulation.Chemokines are important in cell migration and are thought to play a key role in metastasis. We explored the prognostic significance of C-X-C ligand-motif (CXCL) 12, CXCL13, and receptor (CXCR) 5 on disease-free survival (DFS) and overall survival (OS) in early breast cancer.A total of 595 patients with high risk, [corrected] early breast cancer were treated in a 2-arm trial (HE10/97) with dose-dense sequential epirubicin followed by cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) with or without paclitaxel. RNA was extracted from 321 formalin-fixed paraffin-embedded primary tumor tissue samples and quantitative reverse-transcriptase polymerase chain reaction was used to assess messenger RNA (mRNA) expression of CXCL12, CXCL13, and CXCR5; estrogen receptor; progesterone receptor (PgR); microtubule-associated protein tau and human epidermal growth factor receptor 2 (HER2).CXCL13 and CXCR5 were found to be negatively associated with estrogen receptor and microtubule-associated protein tau mRNA expression and with dense lymphocytic infiltration, and were positively associated with nuclear grade. Only CXCL13 was positively associated with HER2. Multivariate analysis revealed an association between high CXCL13 mRNA expression and improved DFS (hazard ratio [HR] 0.48 [95% CI, 0.25-0.90]; Wald, P = .023) but not OS; whereas high CXCL12 expression was significantly associated with increased OS (HR 0.53 [95% CI, 0.33-0.85]; Wald, P = .009). In the HER2 mRNA overexpressing subgroup, high CXCL13 mRNA expression was associated with improved DFS (P.001), whereas high CXCR5 was associated with increased DFS and OS (P = .004 and P = .049, respectively).The CXCL13-CXCR5 axis is associated with classic determinants of poor prognosis, such as high grade, hormone receptor negativity, and axillary node involvement. Interestingly, this chemokine axis seems to be strongly associated with improved outcome in patients with HER2(+) disease.
Databáze: OpenAIRE
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