@article{3089513,
    title = "Improved outcome of high-risk early HER2 positive breast cancer with high CXCL13-CXCR5 messenger RNA expression",
    author = "Razis, E. and Kalogeras, K.T. and Kotoula, V. and Eleftheraki, A.G. and Nikitas, N. and Kronenwett, R. and Timotheadou, E. and Christodoulou, C. and Pectasides, D. and Gogas, H. and Wirtz, R.M. and Makatsoris, T. and Bafaloukos, D. and Aravantinos, G. and Televantou, D. and Pavlidis, N. and Fountzilas, G.",
    journal = "Clinical Breast Cancer",
    year = "2012",
    volume = "12",
    number = "3",
    pages = "183-193",
    publisher = "W B SAUNDERS CO-ELSEVIER INC",
    issn = "1526-8209, 1938-0666",
    doi = "10.1016/j.clbc.2012.03.006",
    keywords = "chemokine receptor CXCR4;  chemokine receptor CXCR5;  CXCL13 chemokine;  cyclophosphamide;  epidermal growth factor receptor 2;  epirubicin;  estrogen receptor;  fluorouracil;  formaldehyde;  granulocyte colony stimulating factor;  messenger RNA;  methotrexate;  paclitaxel;  paraffin;  progesterone receptor;  tau protein, adult;  aged;  article;  breast cancer;  cancer adjuvant therapy;  cancer chemotherapy;  cancer patient;  cancer prognosis;  cancer risk;  cancer staging;  cancer survival;  cancer tissue;  controlled study;  disease free survival;  female;  hazard ratio;  human;  human tissue;  major clinical study;  multiple cycle treatment;  multivariate analysis;  outcome assessment;  overall survival;  protein expression;  protein motif;  quantitative assay;  reverse transcription polymerase chain reaction;  RNA extraction;  tissue fixation;  tumor associated leukocyte",
    abstract = "Background: 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. Methods: A total of 595 patients at high risk for 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). Results: 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). Conclusions: 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. © 2012 Elsevier Inc."
}