Circulating interleukin‐6 predicts survival in patients with metastatic breast cancer

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Abstract
Interleukin‐6 (IL‐6) is a multifunctional cytokine produced by macrophages, T cells, B cells, endothelial cells and tumour cells. Interleukin‐6 is able to promote tumour growth by upregulating anti‐apoptotic and angiogenic proteins in tumour cells. In murine models it has been demonstrated that antibodies against IL‐6 diminish tumour growth. Several reports have highlighted the prognostic importance of IL‐6 in e.g., prostate and colon cancer. We addressed prospectively the prognostic significance of serum IL‐6 (sIL‐6), measured at diagnosis of metastasis, in 96 unselected and consecutive patients with progressive metastatic breast cancer before the initiation of systemic therapy. The median sIL‐6 value for the breast cancer population was 6.6 ± 2.1 pg/ml. Patients with 2 or more metastatic sites had higher sIL‐6 values compared to those with only 1 metastatic site (respectively 8.15 ± 1.7 pg/ml and 3.06 ± 6.6 pg/ml; p < 0.001). Patients with liver metastasis (8.3 ± 2.4 pg/ml), with pleural effusions (10.65 ± 9.9 pg/ml) and with dominant visceral disease (8.15 ± 3.3 pg/ml) had significantly higher values compared to those without liver metastases (4.5 ± 3.4 pg/ml; p = 0.001), without pleural effusions (5.45 ± 1.5 pg/ml; p = 0.0077) and with dominant bone disease (4.5 ± 1.4 pg/ml; p = 0.007) respectively. No correlation between sIL‐6 and age, menopausal status, performance status, tumour grade, body‐mass index, histology and hormone receptor status was found. Multivariate analysis showed that high levels of serum IL‐6 have independent prognostic value. We conclude that circulating IL‐6 is associated with worse survival in patients with metastatic breast cancer and is correlated with the extent of disease.