Plasma Cytokine Levels and Cytokine Genetic Polymorphisms in Patients with Metastatic Breast Cancer Receiving High-Dose Chemotherapy

Differences in the baseline levels of serum cytokines or in single-nucleotide polymorphisms (SNPs) in cytokine genes may be useful to predict outcomes for patients being treated for metastatic breast cancer. We have measured the plasma levels and characterized individual SNPs for IL-1RA, IL-1b, IL-2, IL-6 and TNFa in 130 patients with metastatic breast cancer treated with high-dose chemotherapy. Patients were treated with high-dose cyclophosphamide (Group 1, 74 patients) or high-dose paclitaxel-containing regimens (Group 2, 56 patients). A high plasma level of IL-1RA and a SNP in the IL-1RA gene indicated a better prognosis for patients in Group 1 (but not Group 2). However, the level of plasma IL-1RA did not correlate with the SNP genotype. A high plasma level of IL-6 or TNFa indicated a poorer outcome for patients in Group 1 although the SNP genotypes for the IL-6 and TNFa SNPs were not associated with differences in outcome. The plasma levels of IL-1b and IL-2 and the genotype of the IL-1b SNPs did not indicate differences in outcome. Although, individually, plasma levels of cytokine or “risk” SNP genotypes may not indicate outcome, in combination there was an increased trend to predict outcome for patients treated with high-dose cyclophosphamide but not high-dose paclitaxel. These results suggest that the immune cytokines may be useful as prognostic biomarkers in the treatment of patients with metastatic breast cancer treated with different types of chemotherapy.