CXCR4 expression in early breast cancer and risk of distant recurrence.
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.
Andre
Fabrice
F
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.
Xia
Weiya
W
Conforti
Rosa
R
Wei
Yongkun
Y
Boulet
Thomas
T
Tomasic
Gorana
G
Spielmann
Marc
M
Zoubir
Moustafa
M
Berrada
Narjiss
N
Arriagada
Rodrigo
R
Hortobagyi
Gabriel N
GN
Hung
Mien-Chie
MC
Pusztai
Lajos
L
Delaloge
Suzette
S
Michiels
Stefan
S
Cristofanilli
Massimo
M
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
D018943:Anthracyclines; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4