Investigation of colony stimulating factor-1 receptor (CSF-1R) expression in peripheral monocytes of breast cancer patients for tumor associated macrophages (TAM): A pilot study

Abstract

22221 Background: Colony stimulating factor-1 (CSF-1) mediates macrophage (MØ) differentiation, proliferation, and survival through colony stimulating factor-1 receptor (CSF-1R, c-FMS, CD115). Tumor associated MØ (TAM) express CSF-1R, promote angiogenesis, tumor growth, metastasis, and correlate with adverse prognosis in breast cancer (BC). We asked if CSF-1R+ monocytes (MN) were detectable in the peripheral blood (PB) of patients (pts) with BC and if their presence correlated with adverse prognosis. Methods: From 8/30/05–9/28/07, 228 pts undergoing surgery for stage I-III invasive BC consented to participate in a biomarker trial. Blood samples from 44 pts were sent for analysis of MØ markers. Flow cytometry was used to analyze PB CSF-1R, recorded as the percent of CSF-1R+ MN/total MN. CSF-1R levels from 15 pts without invasive cancer (4 normal, 11 DCIS) and 27 pts treated with neoadjuvant (NA) chemotherapy (CTX) were used as comparison groups. Estimates of 10-year (yr) recurrence and mortality were calculated using Adjuvant! Online program. Linear regression was performed using STATA 9. Results: Mean age was 53 yrs (range 33 - 78 yr). Pts presented with stage I (59%), stage II (29.5%), and stage III (11%) invasive BC. Mean tumor size was 1.8 cm (range 0.2–6.5 cm), 82% of tumors were ER+ and 23% were her2/neu+. Mean percent CSF-1R+ was 24.2% of total MN (range 0–85%). Higher levels of CSF-1R+ correlated with higher estimated 10 yr recurrence and 10 yr mortality (p=0.049, and p=0.004, respectively, by Adjuvant! Online). The mean CSF-1R values were significantly lower for both pts without invasive cancer (7.9% of total monocytes (range 0–32%), p=0.003) and for pts treated with NACTX (14.6% of total MN (range 0–53%), p=0.03). Conclusions: CSF-1R+ MØ are found in tumors that have adverse prognosis and may be part of pathogenesis. We have demonstrated that CSF-1R+ MN can be detected in the PB of BC pts. We are currently validating CSF-1R levels of 100 pts with and without invasive BC, and pts pre and post NA therapy. Correlation between CSF-1R levels in the PB and tumor are underway and will be reported. Agents targeting CSF-1R are in phase I/II trials and CSF-1R+ MN could be an important biomarker for TAM targeted therapy. No significant financial relationships to disclose.