Serum interleukin-6 levels correlate to tumor progression and prognosis in metastatic breast carcinoma.

Serum concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, IL-2 and IL-6 were determined by enzyme-linked immunosorbent assay or chemiluminescent enzyme immunoassay in 46 Japanese patients with metastatic breast cancer. No IL-2 activity was detectable, only two patients had a detectable TNF-alpha level, and 4 had detectable IL-1 beta concentrations. No correlations were found between TNF-alpha and IL-1 beta levels and clinicopathological parameters. Twenty-two patients (48%) showed higher serum IL-6 levels than the cut-off value of 4 pg/ml. Significantly higher IL-6 levels were detected in patients with more than one metastatic site and with dominant metastatic visceral disease than in those with one metastatic site (median, 6.9 vs 1.1 pg/ml, P < 0.0001) or with dominant metastatic bone or soft tissue disease (median, 7.1 vs 2.4, P < 0.05). The patients with liver metastasis and pleural effusion showed significantly higher serum IL-6 levels than those without liver metastases (median, 17.2 vs 2 pg/ml, P = 0.0006) or pleural effusion (median, 12.1 vs 2.1 pg/ml, P = 0.02). A strong correlation was observed between IL-6 levels and C-reactive protein levels (r = 0.47, P = 0.0006). Patients unresponsive to chemo-endocrine therapy showed significantly higher serum IL-6 levels than those who responded to chemo-endocrine therapy (P = 0.0007). Moreover, the patients with high IL-6 levels showed significantly poorer survival than patients with low IL-6 levels. Multivariate analysis revealed that IL-6, as well as disease-free interval, is an independent prognostic factor of metastatic breast cancer. These results suggest that IL-6 levels are elevated and may be an aggressive parameter in patients with metastatic breast cancer. Higher IL-6 serum levels are found to predict a poorer response to chemo-endocrine therapy, and to represent a poorer prognostic predictor in metastatic breast cancer.