title: CXCR4 expression in early breast cancer and risk of distant recurrence.
abstract: BACKGROUND
  Chemokine receptor 4 (CXCR4) has been demonstrated to have a critical role in the early metastatic process. The aim of this study was to evaluate the prognostic value of CXCR4 expression in primary breast tumors and describe correlations with the occurrence of metastasis in organs expressing the CXCR4 ligand stromal cell-derived factor 1 (i.e., liver, lung, brain, and bone).
  
  
  METHODS
  CXCR4 expression in primary breast tumors was evaluated by immunohistochemistry in 823 patients included in two prospective clinical trials. CXCR4 expression was considered positive when >1% of tumor cells were stained. The prognostic value of CXCR4 expression was assessed by a Cox regression model adjusted for clinical characteristics. We assessed the association of CXCR4 expression with the rate of distant metastasis to specific organ sites.
  
  
  RESULTS
  CXCR4 was expressed in 92 of 794 primary tumors (12%). CXCR4 expression was not associated with clinical characteristics. CXCR4 was not prognostic for overall survival and showed a nonsignificant trend toward a higher risk for distant metastasis. CXCR4(+) tumors showed a significantly higher risk for bone metastasis. The 10-year incidences of bone metastases were 23% (13.6%-32.6%) and 12% (9.7%-15%) in CXCR4(+) and CXCR4(-) tumors, respectively.
  
  
  CONCLUSIONS
  This study suggests that expression of CXCR4 in primary breast tumors is associated with a higher likelihood of developing bone metastases. This finding could open new avenues for the development of novel adjuvant strategies, including bone-targeting agents.
authors: Breast Medical Oncology Unit, Department of Radiation Therapy, Department of Pathology and Translational Research Unit (UPRES EA03535), Institut Gustave Roussy, University of Paris XI, Villejuif, France.
authors: Fabrice
authors: F
authors: Andre
authors: Weiya
authors: W
authors: Xia
authors: Rosa
authors: R
authors: Conforti
authors: Yongkun
authors: Y
authors: Wei
authors: Thomas
authors: T
authors: Boulet
authors: Gorana
authors: G
authors: Tomasic
authors: Marc
authors: M
authors: Spielmann
authors: Moustafa
authors: M
authors: Zoubir
authors: Narjiss
authors: N
authors: Berrada
authors: Rodrigo
authors: R
authors: Arriagada
authors: Gabriel N
authors: GN
authors: Hortobagyi
authors: Mien-Chie
authors: MC
authors: Hung
authors: Lajos
authors: L
authors: Pusztai
authors: Suzette
authors: S
authors: Delaloge
authors: Stefan
authors: S
authors: Michiels
authors: Massimo
authors: M
authors: Cristofanilli
mesh_terms: D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D011446:Prospective Studies; D019718:Receptors, CXCR4 / Q000096:biosynthesis*; D015996:Survival Rate
chemical_list: D018943:Anthracyclines; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4