Elevated CSF1 serum concentration predicts poor overall survival in women with early breast cancer

Abstract

Colony-stimulating factor 1 (CSF1) is a key regulator of mammary gland development, and a modulator of tissue macrophages. Expression of the CSF1 receptor gene C-FMS (CSF1R) is strongly associated with poor outcome in breast cancer and results in tumor cell invasiveness and pro-metastatic behavior in vitro. However, CSF1's role as a predictive factor in breast cancer remains unclear. We have prospectively measured circulating CSF1 using ELISA in 572 women with early breast cancer and in 688 women with benign breast lesions, and correlated these concentrations with overall survival (OS), nodal status, and other clinical and histological parameters. Serum CSF1 concentrations were significantly elevated in patients with early breast cancer when compared with those with benign tumors (P<0.0001). Within breast cancer patients, CSF1 was higher in women with axillary lymph nodes (P=0.03). Serum CSF1 correlated with tumor size (P=0.002), age (P<0.001), and Ki67 expression (P=0.006). Log CSF1 serum concentrations were predictive of poor survival in both univariate (hazard ratio (HR): 3.77, 95% CI: 1.65-8.65, P=0.002) and multivariate analyses (HR: 3.1, 95% CI: 1.03-9.33, P=0.04). Post- but not premenopausal women with CSF1 serum concentrations >873 pg/ml experienced a significantly poorer outcome (P=0.004 log-rank test). Serum CSF1 concentrations are elevated in women with malignant breast tumors. In early breast cancer, elevated serum CSF1 is associated with nodal involvement, and in postmenopausal women also with poor OS.