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

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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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References

  1. Ahles TA, Saykin AJ, McDonald BC, Li Y, Furstenberg CT, Hanscom BS, Mulrooney TJ, Schwartz GN, Kaufman PA (2010) Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve. J Clin Oncol. doi:10.1200/JCO.2009.27.0827

    PubMed  Google Scholar 

  2. Janelsins MC, Kohli S, Mohile SG, Usuki K, Ahles TA, Morrow GR (2010) An update on cancer- and chemotherapy-related cognitive difficulties: current status. Sem Onc (in press)

  3. Ahles TA, Saykin AJ (2002) Breast cancer chemotherapy-related cognitive dysfunction. Clin Breast Cancer 3(Suppl 3):S84–S90

    Article  PubMed  CAS  Google Scholar 

  4. Ahles TA, Saykin A (2001) Cognitive effects of standard-dose chemotherapy in patients with cancer. Cancer Invest 19(8):812–820

    Article  PubMed  CAS  Google Scholar 

  5. Quesnel C, Savard J, Ivers H (2009) Cognitive impairments associated with breast cancer treatments: results from a longitudinal study. Breast Cancer Res Treat 116(1):113–123. doi:10.1007/s10549-008-0114-2

    Article  PubMed  Google Scholar 

  6. Wefel JS, Lenzi R, Theriault RL, Davis RN, Meyers CA (2004) The cognitive sequelae of standard-dose adjuvant chemotherapy in women with breast carcinoma: results of a prospective, randomized, longitudinal trial. Cancer 100(11):2292–2299. doi:10.1002/cncr.20272

    Article  PubMed  CAS  Google Scholar 

  7. Wefel JS, Saleeba AK, Buzdar AU, Meyers CA (2010) Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer. Cancer 116(14):3348–3356. doi:10.1002/cncr.25098

    Article  PubMed  Google Scholar 

  8. Vardy J, Wong K, Yi QL, Park A, Maruff P, Wagner L, Tannock IF (2006) Assessing cognitive function in cancer patients. Support Care Cancer 14(11):1111–1118. doi:10.1007/s00520-006-0037-6

    Article  PubMed  Google Scholar 

  9. Castellon SA, Ganz PA, Bower JE, Petersen L, Abraham L, Greendale GA (2004) Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen. J Clin Exp Neuropsychol 26(7):955–969

    Article  PubMed  Google Scholar 

  10. Janelsins MC, Roscoe JA, Palesh OG, Mustian KM, Peppone LJ, Heckler CE, Morrow GR (2010) Cognitive difficulties, fatigue, and sleep in cancer patients at pre-chemotherapy, post-chemotherapy, and at three months follow-up. Annals Behav Med 39(S1); abstract

  11. Magaki S, Mueller C, Dickson C, Kirsch W (2007) Increased production of inflammatory cytokines in mild cognitive impairment. Exp Gerontol 42(3):233–240. doi:10.1016/j.exger.2006.09.015

    Article  PubMed  CAS  Google Scholar 

  12. Galimberti D, Schoonenboom N, Scheltens P, Fenoglio C, Bouwman F, Venturelli E, Guidi I, Blankenstein MA, Bresolin N, Scarpini E (2006) Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease. Arch Neurol 63(4):538–543. doi:10.1001/archneur.63.4.538

    Article  PubMed  Google Scholar 

  13. Galimberti D, Fenoglio C, Lovati C, Venturelli E, Guidi I, Corra B, Scalabrini D, Clerici F, Mariani C, Bresolin N, Scarpini E (2006) Serum MCP-1 levels are increased in mild cognitive impairment and mild Alzheimer's disease. Neurobiol Aging 27(12):1763–1768. doi:10.1016/j.neurobiolaging.2005.10.007

    Article  PubMed  CAS  Google Scholar 

  14. Tan ZS, Beiser AS, Vasan RS, Roubenoff R, Dinarello CA, Harris TB, Benjamin EJ, Au R, Kiel DP, Wolf PA, Seshadri S (2007) Inflammatory markers and the risk of Alzheimer disease: the Framingham Study. Neurology 68(22):1902–1908. doi:10.1212/01.wnl.0000263217.36439.da

    Article  PubMed  CAS  Google Scholar 

  15. Van Den Heuvel C, Thornton E, Vink R (2007) Traumatic brain injury and Alzheimer's disease: a review. Prog Brain Res 161:303–316

    Article  Google Scholar 

  16. Ahles TA, Saykin AJ (2007) Candidate mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer 7(3):192–201. doi:10.1038/nrc2073

    Article  PubMed  CAS  Google Scholar 

  17. Cleeland CS, Bennett GJ, Dantzer R, Dougherty PM, Dunn AJ, Meyers CA, Miller AH, Payne R, Reuben JM, Wang XS, Lee BN (2003) Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine-immunologic model of cancer symptoms. Cancer 97(11):2919–2925. doi:10.1002/cncr.11382

    Article  PubMed  Google Scholar 

  18. Villani F, Busia A, Villani M, Vismara C, Viviani S, Bonfante V (2008) Serum cytokine in response to chemo-radiotherapy for Hodgkin's disease. Tumori 94(6):803–808

    PubMed  CAS  Google Scholar 

  19. Pusztai L, Mendoza TR, Reuben JM, Martinez MM, Willey JS, Lara J, Syed A, Fritsche HA, Bruera E, Booser D, Valero V, Arun B, Ibrahim N, Rivera E, Royce M, Cleeland CS, Hortobagyi GN (2004) Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy. Cytokine 25(3):94–102

    Article  PubMed  CAS  Google Scholar 

  20. Mills PJ, Ancoli-Israel S, Parker B, Natarajan L, Hong S, Jain S, Sadler GR, von Kanel R (2008) Predictors of inflammation in response to anthracycline-based chemotherapy for breast cancer. Brain Behav Immun 22(1):98–104. doi:10.1016/j.bbi.2007.07.001

    Article  PubMed  CAS  Google Scholar 

  21. Roscoe JA, Morrow GR, Hickok JT, Mustian KM, Griggs JJ, Matteson SE, Bushunow P, Qazi R, Smith B (2005) Effect of paroxetine hydrochloride (Paxil) on fatigue and depression in breast cancer patients receiving chemotherapy. Breast Cancer Res Treat 89(3):243–249. doi:10.1007/s10549-004-2175-1

    Article  PubMed  CAS  Google Scholar 

  22. Yoshitake H (1978) Three characteristic patterns of subjective fatigue symptoms. Ergonomics 21(3):231–233

    Article  PubMed  CAS  Google Scholar 

  23. Tangpong J, Cole MP, Sultana R, Joshi G, Estus S, Vore M, St Clair W, Ratanachaiyavong S, St Clair DK, Butterfield DA (2006) Adriamycin-induced, TNF-alpha-mediated central nervous system toxicity. Neurobiol Dis 23(1):127–139. doi:10.1016/j.nbd.2006.02.013

    Article  PubMed  CAS  Google Scholar 

  24. Liedke PE, Reolon GK, Kilpp B, Brunetto AL, Roesler R, Schwartsmann G (2009) Systemic administration of doxorubicin impairs aversively motivated memory in rats. Pharmacol Biochem Behav 94(2):239–243. doi:10.1016/j.pbb.2009.09.001

    Article  PubMed  CAS  Google Scholar 

  25. Cutolo M, Sulli A, Pizzorni C, Seriolo B, Straub RH (2001) Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis. Ann Rheum Dis 60(8):729–735

    Article  PubMed  CAS  Google Scholar 

  26. Cutolo M, Bisso A, Sulli A, Felli L, Briata M, Pizzorni C, Villaggio B (2000) Antiproliferative and antiinflammatory effects of methotrexate on cultured differentiating myeloid monocytic cells (THP-1) but not on synovial macrophages from patients with rheumatoid arthritis. J Rheumatol 27(11):2551–2557

    PubMed  CAS  Google Scholar 

  27. Bouma MG, Stad RK, van den Wildenberg FA, Buurman WA (1994) Differential regulatory effects of adenosine on cytokine release by activated human monocytes. J Immunol 153(9):4159–4168

    PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to thank the following funding sources: NCI R25CA10618 (GRM; MCJ is a fellow) and DOD DAMD17-96-C-6106 (GRM). Additionally, we thank Mr. Eric Hernady for the technical assistance on cytokine ELISAs.

Conflict of interest

The authors have nothing to disclose..

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University of Rochester Medical Center, Rochester, NY, 14642, USA

    Michelle C. Janelsins, Karen M. Mustian, Supriya G. Mohile, Luke J. Peppone, Lisa K. Sprod, Charles E. Heckler, Joseph A. Roscoe, Alan W. Katz, Jacqueline P. Williams & Gary R. Morrow

  2. Department of Community and Preventive Medicine, University of Rochester Medical Center, Rochester, NY, 14642, USA

    Karen M. Mustian

  3. Department of Psychiatry and Behavioral Sciences, Stanford University, 401 Quarry Road, Stanford, CA, 94305, USA

    Oxana G. Palesh

  4. Department of Medicine, University of Rochester Medical Center, Rochester, NY, 14642, USA

    Supriya G. Mohile

  5. Department of Psychiatry, University of Rochester Medical Center, Rochester, NY, 14642, USA

    Gary R. Morrow

Authors
  1. Michelle C. Janelsins
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  2. Karen M. Mustian
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  3. Oxana G. Palesh
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  4. Supriya G. Mohile
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  6. Lisa K. Sprod
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  7. Charles E. Heckler
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  8. Joseph A. Roscoe
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  9. Alan W. Katz
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  10. Jacqueline P. Williams
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Corresponding author

Correspondence to Michelle C. Janelsins.

Additional information

This paper was presented as an invited oral presentation at the MASCC/ISOO 2010 International Symposium in Vancouver, Canada.

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Janelsins, M.C., Mustian, K.M., Palesh, O.G. et al. Differential expression of cytokines in breast cancer patients receiving different chemotherapies: implications for cognitive impairment research. Support Care Cancer 20, 831–839 (2012). https://doi.org/10.1007/s00520-011-1158-0

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  • DOI: https://doi.org/10.1007/s00520-011-1158-0

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