An evaluation of bone marrow stromal-derived growth factor-1 and interleukin-8 levels in patients with stage I-III breast cancer with disseminated tumor cells.

Abstract

10610 Background: Tumor cells that disseminate to the bone marrow (disseminated tumor cells, or DTCs), have been identified in 30% of stage I-III breast cancer (BC) patients and are known to predict outcome. However, the mechanisms involved in DTC metastasis to the bone marrow are unknown. We hypothesized that increases in bone turnover may result in the release of bone growth and “homing” factors into the bone marrow, facilitating BC metastasis to bone marrow and providing a “pre-metastatic niche” for BC cells. The purpose of this study was to determine if bone marrow plasma levels of two well characterized BC-bone “homing” chemokines, stromal-derived growth factor-1 (SDF-1) and interleukin-8 (IL-8), are increased in BC patients with DTCs. Methods: Sixty-five clinical stage I-III BC patients provided informed consent to participate in an IRB-approved study involving collection of bone marrow at the time of surgery for their primary BC. DTCs were assessed using an anti-cytokeratin antibody cocktail following ficoll enrichment and cytospin. Bone marrow plasma SDF-1 and IL -8 levels were quantified using enzyme-linked immunoassays. Results: Mean age was 54 years. Eighty-two percent of patients had T1/T2 tumors, and 38% had lymph node metastases. DTCs were identified in 12/65 (18.5%) of patients. No statistically significant correlations were observed between primary tumor characteristics (ER, PR, HER2, lymph node status, tumor grade) and presence of DTCs. Mean bone marrow plasma SDF-1 levels (1359 ± 379 pg/mL vs. 525 ± 312 pg/mL; p ≤0.001) and IL-8 levels (559 ± 108 pg/mL vs. 62 ± 45 pg/mL; p≤0.001) were significantly higher in DTC-positive vs. DTC-negative patients. Conclusions: Bone marrow plasma SDF-1 and IL-8 levels were significantly increased in patients with DTCs compared to DTC-negative patients. Further studies are needed to determine if patients harboring DTCs have unique microenvironmental factors within the bone marrow that predispose them to tumor cell dissemination.