IL-6 is differentially expressed in the tumors of breast cancer patients treated with trastuzumab.
Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased manner the most striking transcriptional features of trastuzumab treatment. We identified the cytokine interleukin-6 (IL-6) (5) as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed higher levels of IL-6 messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of IL-6 in primary tumors of the breast, suggesting that increased primary tumor expression of IL-6 in the primary tumors of patients with breast cancer, a cytokine whose serum levels are correlated with worse patient survival outcomes in metastatic breast cancer (6), is a direct transcriptional result of treatment with trastuzumab.