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Plasma Stromal Cell–Derived Factor-1: Host Derived Marker Predictive of Distant Metastasis in Breast Cancer

Authors' Affiliations: ¹ Departments of Oncology and Surgery, Lady Davis Institute, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, Quebec, Canada; ² EPOCA Epidemiology Research Center, Center of Molecular and Genetic Epidemiology, University of Milan and IRCCS Maggiore Policlinico Hospital, Mangiagalli and Regina Elena, Milan, Italy; and ³ Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland

Requests for reprints: Mark Basik, Department of Oncology, Lady Davis Institute, Sir Mortimer B. Davis Jewish General Hospital, McGill University, 3755 Cote Ste Catherine, Montreal, Quebec, Canada H3T 1E2. Phone: 514-340-8222, ext. 4930; Fax: 514-340-8716; E-mail: mark.basik{at}mcgill.ca.

Purpose: Homing of breast cancer cells to metastatic sites may be regulated by the production of stromal cell–derived factor (SDF)-1 by specific target organs, which attracts CXCR4-expressing breast cancer cells. We investigated the value of SDF-1 as a predictive blood marker of distant metastasis in breast cancer, together with a common polymorphism of SDF-1, SDF-1-3'A.

Experimental Design: Plasma samples were collected prospectively for 270 consecutive primary breast cancer patients with a median follow-up of 3.3 years. Plasma SDF-1 levels were measured using an ELISA, and the polymorphism was identified via PCR-RFLP analysis.

Results: Plasma SDF-1 levels were divided into two groups, low and high, based on the median SDF-1 value of 2,661 pg/mL. Patients with low SDF-1 showed an increased risk of developing distant metastasis (relative risk, 1.94; P = 0.02) and poorer breast cancer–specific survival [adjusted hazard ratio (AHR), 3.92; P = 0.007]. Patients with both low plasma SDF-1 levels and the SDF-1-3'A polymorphism showed a poorer breast cancer–specific survival (AHR, 3.98; P = 0.001) and distant disease-free survival (AHR, 2.88; P = 0.003). In a separate cohort of 22 breast cancer patients, we found no significant difference in SDF-1 levels before and posttumor resection.

Conclusion: We found that low plasma SDF-1 is an independent host-derived predictive marker of distant metastasis in breast cancer. The prognostic value of the combination of a low plasma SDF-1 level and the SDF-1-3'A polymorphism identifies a cohort of patients with an intrinsic susceptibility for poorer survival.