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Randomized Controlled Trial
. 2012 Apr;20(4):831-9.
doi: 10.1007/s00520-011-1158-0. Epub 2011 May 1.

Differential expression of cytokines in breast cancer patients receiving different chemotherapies: implications for cognitive impairment research

Michelle C Janelsins  1 , Karen M Mustian, Oxana G Palesh, Supriya G Mohile, Luke J Peppone, Lisa K Sprod, Charles E Heckler, Joseph A Roscoe, Alan W Katz, Jacqueline P Williams, Gary R Morrow
Affiliations
Randomized Controlled Trial

Differential expression of cytokines in breast cancer patients receiving different chemotherapies: implications for cognitive impairment research

Michelle C Janelsins et al. Support Care Cancer. 2012 Apr.

Abstract

Purpose: Altered levels of cytokines and chemokines may play a role in cancer- and cancer treatment-related cognitive difficulties. In many neurodegenerative diseases, abnormal concentrations of cytokines and chemokines affect neuronal integrity leading to cognitive impairments, but the role of cytokines in chemotherapy-related cognitive difficulties in cancer patients is not well understood. Patients receiving doxorubicin-based (with cyclophosphamide, or cyclophosphamide plus fluorouracil; AC/CAF) chemotherapy or cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy report experiencing cognitive difficulties; because these regimens work by different modes of action, it is possible that they differentially affect cytokine levels.

Methods: This study examined the relationships between cytokine levels (i.e., IL-6, IL-8, and MCP-1) and type of chemotherapy among 54 early-stage breast cancer patients receiving AC/CAF or CMF. Cytokine levels were assessed at two time-points: prior to on-study chemotherapy cycle 2 (cycle 2) and after two consecutive chemotherapy cycles (prior to on-study cycle 4; cycle 4).

Main results: Analyses of variance using cycle 2 levels as a covariate (ANCOVA) were used to determine differences between chemotherapy groups. Levels of IL-6, IL-8, and MCP-1 increased in the AC/CAF group and decreased in the CMF group; the only significant between-group change was in IL-6 (p < 0.05).

Conclusions: These results, although preliminary based on the small sample size, suggest that AC/CAF chemotherapy is more cytokine inducing than CMF. Future studies should confirm these results and explore the distinct inflammatory responses elicited by different chemotherapy regimens when assessing cognitive function in cancer patients.

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Figures

Figure 1
Figure 1. Inflammation induced by chemotherapy as a possible mechanism of cognitive difficulties in breast cancer patients
Multiple factors can contribute to cognitive difficulties in cancer patients. During treatment, inflammation caused by tissue damage from chemotherapy may contribute to cognitive difficulties in cancer patients.
Figure 2
Figure 2
Study Schema
Figure 3
Figure 3
(A) Comparison of cytokine and chemokine levels among chemotherapy groups (B) Mean changes in MCP-1, IL-6 and IL-8 according to chemotherapy regimen
Figure 3
Figure 3
(A) Comparison of cytokine and chemokine levels among chemotherapy groups (B) Mean changes in MCP-1, IL-6 and IL-8 according to chemotherapy regimen
Figure 4
Figure 4
(A) Characterization of Cognitive Difficulties in Breast Cancer Patients Undergoing Chemotherapy (B-C) Correlations between Changes in Cognitive Function and Cytokine/Chemokine Levels in AC/CAF and CMF Chemotherapy Groups
Figure 4
Figure 4
(A) Characterization of Cognitive Difficulties in Breast Cancer Patients Undergoing Chemotherapy (B-C) Correlations between Changes in Cognitive Function and Cytokine/Chemokine Levels in AC/CAF and CMF Chemotherapy Groups
Figure 4
Figure 4
(A) Characterization of Cognitive Difficulties in Breast Cancer Patients Undergoing Chemotherapy (B-C) Correlations between Changes in Cognitive Function and Cytokine/Chemokine Levels in AC/CAF and CMF Chemotherapy Groups
See this image and copyright information in PMC

References

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