Abstract

PURPOSE: Following therapy, breast cancer survivors have impaired immune functions which are associated with increased risk of recurrence and infectious diseases. Neutrophils are critical to host protection against infectious diseases. The aim of this study was to use acute exercise as an immunological stressor before and after 16-weeks of exercise training to determine changes in neutrophil functions consistent with a reduced infection risk. METHODS: 16 breast cancer (BC) survivors completed 45 minutes of intermittent cycling at 60% of peak CPX wattage before (BASE) and after 16-weeks (FINAL) of exercise training. Eleven healthy sedentary women (Control) completed the same acute bout of exercise at BASE. Blood was taken at rest (PRE), immediately after (POST) and 1 hour after (1Hr POST) exercise. Neutrophil phagocytosis and oxidative killing of E.coli, and expression of CD16, CXCR2 and TLR4 were assessed by flow cytometry (MFI ± SD). RESULTS: Compared to Controls, at BASE PRE, BC survivors had lower phagocytosis of bacteria (4250±718 v 3991±1232; p=0.03), and elevated oxidative burst (4495±651 v 6254±1434; p=0.005). At BASE, BC survivors’ phagocytic response to acute exercise was impaired. BC survivors PRE to POST phagocytosis was unchanged (p=0.224) while Controls increased 15±20% (p=0.003). BC survivors PRE to 1Hr POST phagocytosis increased by 10±17% (p=0.046) while Controls increased 14±14% (p=0.003). Following training, BC survivor PRE phagocytosis increased from BASE to FINAL by 10% (p=0.08), to similar levels as Controls (p=0.765). BC survivors FINAL PRE to POST phagocytosis increased by 10% (p=0.001) and PRE to 1Hr POST by 11% (p=0.008). Oxidative killing of bacteria was unchanged by acute exercise or exercise training. At BASE, BC survivor expression of CD16 reduced during acute exercise, PRE to 1Hr POST by 9% (p=0.04) which annulled following training. CONCLUSIONS: Following cancer therapy, BC survivors have impaired neutrophil functions at rest and to a stressor, which are improved by 16-weeks of exercise training. The improved phagocytosis of bacteria in BC survivors may represent an intrinsic improvement in neutrophil functions consistent with reduced risk of infectious disease. Supported by Breast Cancer Research Foundation (New York, NY).

Highlights

  • Recent advances in breast cancer detection and treatment have increased 5-year survival rates to approximately 90% [1]

  • For the first time that we are aware of, we have recently described in breast cancer survivors (BCS) the acute exercise-mediated monocyte [25] and mucosalassociated invariant T-cell (MAIT) [26] responses before and after 16 weeks of exercise training

  • Neutrophils are the first immune cell to respond against infectious organisms, and breast cancer survivors are at an increased risk of infections due to treatment-related immune suppression [3, 29]

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Summary

Introduction

Recent advances in breast cancer detection and treatment have increased 5-year survival rates to approximately 90% [1]. Following the completion of therapy, breast cancer survivors (BCS) suffer prolonged immune suppression, increasing the risk of recurrence, metastasis, and microbial infections [2, 3]. Neutrophils are the first immune cell to respond against microorganisms and are functionally suppressed during and after chemotherapy and surgery [4, 5]. Neutrophil functional responses are stimulated by inflammatory cytokines, including IL-6 and IL-8 [6]. Chronic exposure to inflammation, as seen in breast cancer, can generate neutrophils with suppressed microbial functions [7]. Interventions that improve BCS neutrophil functions may reduce the risk of infections following the completion of therapy

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