Purpose: Interleukin-6 (IL-6) is a pleiotropic cytokine that can act as an autocrine or paracrine cancer cell growth factor and contributes to recurrence and metastasis in several types of cancer. The present case-control study was conducted to investigate the predictive and prognostic significance of serum IL-6 in breast cancer.

Methods: Fifty-six consecutive patients with primary breast cancer were prospectively included and evaluated. The control group consisted of 45 healthy women. Serum concentrations of IL-6 were measured by quantitative sandwich enzyme immunoassay (ELISA).

Results: Serum levels of IL-6 were significantly increased in breast cancer patients compared to healthy controls  6.85 pg/ml vs. 1.49 pg/ml,  For the evaluation of the diagnostic significance of serum IL-6, the area under the receiver operating characteristic (ROC) curve (AUC) was 0.931, while the optimal cut-off point of 4.20 pg/ml was determined to classify breast cancer patients, which yielded sensitivity of 96%, specificity of 89% and accuracy of 93.1%. Significantly elevated serum IL-6 levels were associated with invasive tumors  immunohistochemical HER-2 overexpression  more than three positive lymph nodes  and advanced stages  In multivariate linear regression analysis, the presence of more than three positive lymph nodes  remained the only significant independent determinant of high IL-6 levels  With regard to prognostic significance for more than three positive lymph nodes (AUC, 0.813), when the optimal cut-off value was set at 7.00 pg/ml, the sensitivity was 79%, the specificity was 77% and the accuracy was 78%. Survival was shorter in patients with increased serum IL-6  months vs. 43 months,  Multivariate analysis demonstrated a significant independent prognostic significance of serum IL-6 for survival  hazard ratio = 4.0, 95% CI = 1.2 to

Conclusions: Our findings suggest that serum IL-6 is involved in tumor malignancy and lymph node metastasis and could be used clinically as a useful tumor marker for the diagnosis, the extension and the outcome of the disease.

serum IL-6, diagnosis, prognosis, breast cancer, survival.