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Systemic immune effects of adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide and/or radiotherapy in breast cancer: a longitudinal study

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Abstract

Immunotherapy is being increasingly utilized for adjuvant treatment for breast cancer (BC). We have previously described immune functions during primary therapy for BC. The present study describes immune recovery patterns during long-term, unmaintained follow-up after completion of adjuvant therapy.A group of patients with primary BC had been treated with adjuvant radio-chemotherapy (RT + CT) 5-fluorouracil, epirubicin and cyclophosphamide (FEC) (n = 21) and another group with radiotherapy (RT) (n = 20) alone. Immunological testing of NK and T-cell functions was performed initially at the end of adjuvant treatment and repeated after 2, 6 and 12 months. NK cell cytotoxicity was significantly higher (P < 0.05) at all time-points in patients than in age-matched controls and did not differ between the two treatments groups during one year observation. In contrast, lower numbers of CD4 T-cells and lower expression of CD28 on T-cells was observed particularly in RT + CT patients and did not normalize during the observation period. The numbers of Treg cells (CD4+CD25high) were low in the RT + CT group during follow-up, as well as expression of TCRξ, Zap70, p56lck, P59fyn and PI3 k in CD4+ cells. In contrast, expression of intracellular cytokines (IFN-γ, IL-2, IL-4) in CD4 and CD8 T cells were significantly higher in RT + CT patients than in the RT group and the difference increased during follow-up. In conclusion, NK-cell cytotoxicity increased during unmaintained long-term follow-up whereas CD4 and regulatory T cells as well as signal transduction molecules remained low following adjuvant radio-chemotherapy.

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Acknowledgments

This study was supported by grants from Sparbanksstiftelsen Nya Västerås, Cancer and Allergy Foundation, The Research Foundation of Västmanland, Cancer and Traffic Injury Fund, and the County Council of Västmanland. We thank Ms. Birgitta Hagström for her expert technical assistance and Ms. Leila Relander for help with preparing the manuscript.

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Authors and Affiliations

  1. Immune and Gene Therapy Laboratory, Cancer Centre Karolinska, Karolinska University Hospital Solna, Stockholm, Sweden

    Fariba Mozaffari, Christina Lindemalm, Aniruddha Choudhury, Anders Österborg & Håkan Mellstedt

  2. Department of Oncology, Central Hospital, Västerås, Sweden

    Helena Granstam-Björneklett

  3. Department of Clinical Neuroscience, Osher Center for Integrative Medicine and Section of Psychology, Karolinska Institutet, Stockholm, Sweden

    Mats Lekander

  4. Department of Cancer Epidemiology, Karolinska University Hospital Solna, Stockholm, Sweden

    Bo Nilsson

  5. Centre for Clinical Research, Uppsala University, Central Hospital, Västerås, Sweden

    Marja-Leena Ojutkangas & Leif Bergkvist

  6. Departments of Hematology and Oncology, Karolinska University Hospital Solna, Stockholm, Sweden

    Anders Österborg & Håkan Mellstedt

  7. Department of Surgery, Central Hospital, Västerås, Sweden

    Leif Bergkvist

  8. Department of Oncology (Radiumhemmet), Karolinska University Hospital, 171 76, Stockholm, Sweden

    Håkan Mellstedt

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  1. Fariba Mozaffari
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Correspondence to Håkan Mellstedt.

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Mozaffari, F., Lindemalm, C., Choudhury, A. et al. Systemic immune effects of adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide and/or radiotherapy in breast cancer: a longitudinal study. Cancer Immunol Immunother 58, 111–120 (2009). https://doi.org/10.1007/s00262-008-0530-5

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