Background

Experimental Design & Methods

LEUKOCYTE, LEUKOCYTE SUBSETS, AND INFLAMMATORY CYTOKINE RESPONSE TO RESISTANCE EXERCISE IN BREAST CANCER SURVIVORS

Robert C. Mills1,3, Rachel Graff1,3, Jacob Allen1,3, Claudio L. Battaglini, FACSM1,2,3, Eric Ryan3, A.C. Hackney, FACSM1,3,4

1UNC EXERCISE ONCOLOGY RESEARCH LAB, 2LINEBERGER COMPREHENSIVE CANCER CENTER, 3DEPARTMENT OF EXERCISE AND SPORT SCIENCE, 4NUTRITION, UNIVERSITY OF NORTH CAROLINA, CHAPEL HILL, NC

Purpose

Conclusions

ResultsPhysical Characteristics and Strength Breast Cancer Survivors

(mean ± SD)Controls

(mean ± SD)Age (yrs) 60 ± 12 56 ± 7Height (cm) 168.6 ± 3.1 163.7 ± 6.8 Weight (kg) 75.6 ± 13.4 67.2 ± 6.3 Body Fat (%) 37.6 ± 10.3 37.6 ± 4.5 1-RM Leg Press (kg) 81.6 ± 20 79.5 ± 14.51-RM Lat Pull Down (kg) 33.2 ± 5.5 35.8 ± 6.81-RM Leg Extension (kg) 58.4 ± 15.1 60.3 ± 12.51-RM Seated Row (kg) 34.1 ± 5.3 38.8 ± 3.9

Abstract

Supported by UNC Lineberger Comprehensive Cancer Center and the Petro Kulynych Foundation

PURPOSE: The purpose of this pilot study was to examine the immune and inflammatory response to a single bout of moderate-intensity resistance exercise (RE) in breast cancer survivors (BCS). METHODS: BCS (n=4) and healthy controls (C) (n=8) completed an exercise session consisting of 3 sets of 10 repetitions at 70% of one repetition-maximum on leg press, lateral pull down, leg extension, and seated row performed in a circuit fashion. Blood samples were taken at baseline, immediately post (0h post), 2-hours post (2h post), and 24-hours post (24h post) exercise and assessed for total leukocyte, granulocyte, lymphocyte, monocyte cell counts, and Interleukin 6 (IL-6), Interleukin 10 (IL-10), Tumor Necrosis Factor- α (TNF- α). Percent change (%Δ) scores from baseline-0h post, baseline-2h post, and baseline-24h post were compared using mixed-model ANOVAs. RESULTS: There were no significant differences between total leukocytes (p=0.560), granulocytes (p=0.239), lymphocytes (p=0.257), or monocytes (p=0.721), nor differences between groups for each of the cytokines at each time point after exercise. However, the RE did cause a significant up-regulation in IL-6 at 2-hours post (p=0.027) and a significant down-regulation of TNF- α at 24-hours post in both groups (p=0.011). CONCLUSION: Findings suggest that no difference exists in the immune or inflammatory response due to RE between BCS and C. However, an anti-inflammatory response into recovery (i.e., decreased TNF- α at 24-hours post) was observed in both groups. Large sample sizes are needed to support these findings.

•Acute, post-exercise inflammation is defined by intricate interactions between cytokines, catabolic hormones, acute phase proteins and immune cells which ultimately leads to variability in the internal endocrine and paracrine milieu (Pederson, 2000; Nieman, 2004).

•A well functioning immune system plays an integral role in maintaining overall health and optimal physiological function. However, cancer and its treatments are associated with higher inflammatory state and immunodeficiency, which often lasts well beyond the completion of treatments and have been postulated to increase risk of secondary infection as well as a risk of cancer recurrence (Fairey et al., 2005; Hutnick et al., 2005).

•As a population that often experience chronic inflammation and immunosuppression, cancer survivors are in need of interventions that promote less inflammation and boost the immune system as a preventative strategy to improve overall health and reduce chances of poorer long term prognosis.

•To date, few studies have examined the acute effects of exercise on the inflammatory and immune system responses in breast cancer patients (Peters et al., 1994; Nieman et al., 1995; Fairey et al. 2005). Furthermore, most of these studies have looked at chronic aerobic exercise with no studies to date examining the effects of resistance training. Examining markers of immunity and the inflammatory response to an acute exercise bout may serve as an important initial step for the development of more precise exercise prescriptions aimed to alleviate inflammation and improve immune function in breast cancer survivors.

The purpose of this pilot study was to examine the immune and inflammatory response to a single bout of moderate-intensity resistance exercise in breast cancer survivors and to compare these responses to a group of age, fitness level, matched apparently healthy women.

Breast Cancer Survivors (n = 4) Controls (n = 8)Diagnosed with Stage I-III invasive breast cancerReceived chemotherapyCompleted surgery, chemotherapy, and radiation therapy within 3-6 months prior to enrollment

No history of cancer diagnosis or treatment

Women, ages 40-70 yearsPhysically inactive for ≥ 1 yearPost-menopausal for ≥ 1 year

Not regular users of anti-inflammatory medications

Baseline Physiological Assessments

Parameter Assessment MethodHeight Stadiometer (Perspective Enterprises, Portage, MI)Body Mass Mechanical Scale (Detecto, Webb City, MO)Resting Electrocardiogram GE Case Cardiosoft V. 6.6 ECG Diagnositic System

(General Electric, Palatine, IL)Percent Body Fat Dual Energy X-ray Absorption (DEXA) scanner

(Hologic, Inc., Bedford, MA)Muscular Strength 1-RM

Acute Resistance Exercise Bout and Blood Sampling•3x10 repetitions at 70% of 1-RM of each exercise (leg press, lateral pull down, leg extension, and seated row, respectively) with 30 to 45 seconds of rest between sets, and 1:30 seconds to 2 minutes of rest between subsequent circuits.•Whole blood samples taken pre-exercise, immediately post-exercise, 2 hours post-exercise, and 24 hours post-exercise using a 22 gage Protectiv Plus catheter. The fourth sample was done using standard venipuncture techniques.

Parameter Measurement MethodTotal Leukocyte, Granulocyte, Lymphocyte, and Monocyte Counts

COULTER® Ac•T diff™ Hematology Analyzer (Beckman Coulter, Inc., Brea, CA)

IL-6, IL-10 and TNF-α Enzyme linked immunosorbent assays (ELISA) Biolegend (San Diego, USA)

Statistical Analysis2x4 mixed model ANOVA, Bonferonni post-hoc, and independent samples t-tests

• There were no significant differences found between breast cancer survivors and healthy controls for total leukocytes, granulocytes, lymphocytes, or monocytes based on percent change (%Δ) scores.

• There were no significant differences observed between groups for IL-6, IL-10, or TNF- α at each time point after exercise.

• The results of this study suggest that breast cancer survivors and healthy age-matched controls exhibit similar immune and inflammatory responses to an acute bout of resistance training.

• However, due to the small sample size and the preliminary nature of this study, more research is needed to confirm or refute these findings.No significant differences were found between the BCS and Control groups for any physical characteristics and strength at baseline

*Denotes statistical significance (p ≤ 0.05) when compared to baseline. †Denotes statistical significance (p ≤ 0.05) between BCS and control groups.

No significant differences were found between the breast cancer survivor group and the control group using % Δ scores (baseline to all post-exercise time points) for any of the dependent variables.

*References available upon request