The Study Of Risk Factors And The Correlation Of NF-κB And GM-CSF With Bone Metastasis In Breast Cancer

Objective:In order to investigate the risk factors correlated with bone metastasis in post-operative breast cancer patients, we performed this study focusing on the nuclear factor-κB and granulocyte-macrophage colony-stimulating factor.Methods :We collected detailed information of 124 breast cancer patients who received surgery in the Department of General Surgery, Shanghai Sixth People's Hospital from January 2000 to December 2007. The HER-2 status was assessed by immunohistochemistry (IHC). The (-/+) results were defined as negative, while the (++) and (+++) ones were further confermed by fluorescence in situ hybridization (FISH). The expression of NF-κB and GM-CSF was measured by IHC in the 124 patients. Univariate and multivariate analysis were used to study the correlation between bone metastasis and NF-κB,GM-CSF and other clinical pathological factors.Results:1. There were 52 patients defined as (++) and (+++) by IHC, among whom 40 patients were comfirmed as FISH positive.2.In the 52 patients with bone metastases, the common metastasted sites were lumbar vertebrae, thoracic vertebrae, pelvis and ribs. The median time to bone metastasis was 32 months. Univariate analysis showed that tumor size (T1-3) and lymph node status were significantly different between bone metastasis group and non-bone metastasis ones (30.8% vs 40.4% vs 75.0%, P = 0.003) and (21.4% vs 40.9% vs 64.3% vs 72.2%, P =0.000), respestively. Meanwhile, there were more HER-2 positive patients in the bone metastasis group (55.0% vs 35.7%, P =0.042). However, age, menopausal status, histological grade, ER, P53, tumor location and pathological type were not different between breast cancer bone metastasis group and non-bone metastasis group.3. There were more patients with NF-κB-positive (69.2% vs 41.7%, P =0.002) and GM-CSF negative (63.4% vs 36.1%, P =0.001) in the bone metastasis group than the non-bone metastasis group, respectively. However, the correlation between the expression of NF-κB and GM-CSF was not significant (P=0.490). Patients with multiple bone metastatic lesions were tended to have NF-κB positive (81.1% vs 40.0%, P =0.010), while this relationship was not found with the expression of GM-CSF (P=0.245).4. Multivariate analysis showed that tumor size, lymph node status, histological grade and the expression of HER-2, NF-κB and GM-CSF were risk factors for bone metastasis in breast cancer patients.Conclusions:1. NF-κB and GM-CSF were important factors in development of bone metastasis in breast cancer patients.2.More lymph node metastasis, large tumor size, high histologic grade, HER-2 positive, NF-κB positive and GM-CSF negative were risk factors for bone metastasis.