DIAGNOSTIC AND PROGNOSTIC SIGNIFICANCE OF SERUM IL-6 LEVELS IN BREAST CANCER

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 (median, 6.85 pg/ml vs. 1.49 pg/ml, p < 0.001). 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 cutoff 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 (p = 0.049), immunohistochemical HER-2 overexpression (p = 0.037), more than three positive lymph nodes (p = 0.006) and advanced stages (p = 0.064). In multivariate linear regression analysis, the presence of more than three positive lymph nodes (p = 0.009) remained the only significant independent determinant of high IL-6 levels (R-2 = 27.2%). 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 (35 months vs. 43 months, p = 0.043). Multivariate analysis demonstrated a significant independent prognostic significance of serum IL-6 for survival (p = 0.029; hazard ratio = 4.0, 95% CI = 1.2 to 13.9). 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.