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Breast Cancer

CXCR4 Expression in Early Breast Cancer and Risk of Distant Recurrence

^aBreast 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; ^bDepartment of Breast Medical Oncology and ^cDepartment of Molecular and Cellular Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA; ^dUnit of Biostatistics and Epidemiology, Institut Gustave Roussy, Villejuif, France

Key Words. CXCR4 expression • Breast cancer • Recurrence • Bone metastases

Correspondence: Massimo Cristofanilli, M.D., F.A.C.P., Department of Breast Medical Oncology - Unit 1354, The University of Texas, M. D. Anderson Cancer Center, PO Box 301439, Houston, Texas 77230, USA. Telephone: 713-792-2817; Fax: 713-794-4385; e-mail: mcristof{at}mdanderson.org

Received July 21, 2009; accepted for publication October 13, 2009; first published online in THE ONCOLOGIST Express on November 25, 2009.

Disclosures

Fabrice Andre: None; Weiya Xia: None; Rosa Conforti: None; Yongkun Wei: None; Thomas Boulet: None; Gorana Tomasic: None; Marc Spielmann: None; Moustafa Zoubir: None; Narjiss Berrada: None; Rodrigo Arriagada: None; Gabriel N. Hortobagyi: None; Mien-Chie Hung: None; Lajos Pusztai: None; Suzette Delaloge: None; Stefan Michiels: None; Massimo Cristofanilli: None.

Section editor Kathleen Pritchard has disclosed no financial relationships relevant to the content of this article. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias.

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).

Patients and 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.

Conclusion. 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.