Expression of Inflammatory Molecules Among Breast Cancer Patients Receiving Different Chemotherapies:Implications for Chemobrain

Increased levels of MCP-1, IL-8 and IL-6 are associated with mild cognitive impairment, defined as frequent and irregular bouts of forgetfulness, difficulties with attention and/or difficulties with language-a condition with comparable symptomology reported by cancer patients experiencing chemobrain. High levels of these molecules may compromise neuronal and synaptic integrity, leading to cognitive impairment. Patients receiving doxorubicin-based (with cyclophosphamide, or cyclophosphamide and fluorouracil; AC/CAF) chemotherapy or a combination of cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy report experiencing chemobrain, but MCP-1, IL-8 and IL-6 may be differentially influenced by these regimens. The purpose of this study was to examine changes in expression of these molecules among breast cancer patients (N = 54) receiving combinations of AC/CAF or CMF. Changes in MCP-1, IL-8 and IL-6 were assessed at baseline (T1) and after 2 chemotherapy cycles (T2). T-tests were used to compare between group and within group differences on raw means and mean change (T2-T1). IL-6 significantly increased in the AC/CAF group (4.95 pg/mL,SEM = 2.31;P < 0.05), but MCP-1 (42.8 pg/mL;SEM = 40.36) and IL-8 (0.25 pg/mL;SEM = 1.19) did not. IL-6 (−1.46 pg/mL,SEM = 0.94), MCP-1 (−15.8 pg/mL,SEM = 49.95) and IL-8 (−0.79 pg/mL,SEM = 1.04) all decreased in the CMF group; however, none of these changes were significant. No significant differences in IL-6 (1.06 pg/mL, SEM = 1.05), MCP-1(73.48 pg/mL, SEM = 67.30), or IL-8 (−1.95 pg/mL, SEM = 3.28) at T1 were observed between AC/CAF and CMF groups. At T2, there was a significant difference in IL-6 (7.72 pg/mL,SEM = 3.82; P ≤ 0.05) between AC/CAF and CMF groups, but not in MCP-1 (131.91 pg/mL,SEM = 87.09) or IL-8 (5.72 pg/mL,SEM = 4.0). A significant change (T2-T1) in IL-6 (6.41 pg/mL,SEM = 2.57;P < 0.05) between AC/CAF and CMF groups was observed. Changes in MCP-1 (58.65 pg/mL,SEM = 63.94) and IL-8 (1.08 pg/mL,SEM = 1.58) between groups were not significant. These results suggest AC/CAF and CMF chemotherapy regimens elicit distinct inflammatory response patterns in MCP-1, IL-8 and IL-6 suggesting different mechanisms may be responsible for the development of chemobrain. Future research is needed to confirm these findings. Funding:NCI R25CA10618.