Effect of exercise training on C-reactive protein in postmenopausal breast cancer survivors: A randomized controlled trial

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Abstract

The objective of this study was to determine the effects of exercise training on changes in C-reactive protein (CRP) and other cardiovascular risk factors in postmenopausal breast cancer survivors. Fifty-three postmenopausal breast cancer survivors were randomly assigned to an exercise (n = 25) or control group (n = 28). The exercise group trained on cycle ergometers 3 times per week for 15 weeks. The control group did not train. The primary end point was change in CRP between baseline and week 15. Secondary end points were changes in RHR, HRR, SBP, DBP, TC, LDL-C, HDL-C, TG, and TC:HDL-C ratio. Fifty-two participants completed the trial. Baseline values did not differ between groups except that TG (p = .007) and TC:HDL-C ratio (p = .023) were higher in the exercise group. Intention-to-treat analysis showed that CRP decreased by 1.39 mg/L in the exercise group whereas it increased by 0.10 mg/L in the control group (mean between group change, −1.49 mg/L; 95% CI, −3.09 to 0.10 mg/L; p = .066). Intention-to-treat analysis also showed a clinically and statistically significant difference between groups for change in HRR (mean change, +10.6 beats/min; 95% CI, +3.4 to +17.7 beats/min; p = .004) and clinically but not statistically significant differences between groups for change in RHR (mean change, −5.5 beats/min; 95% CI, −11.5 to +0.5 beats/min; p = .073), SBP (mean change, −5.5 mm Hg; 95% CI, −14.5 to +3.4 mm Hg; p = .218), DBP (mean change,−3.6 mm Hg; 95% CI, −9.3 to +2.1 mm Hg; p = .214), and HDL-C (mean change, +0.05 mmol/L; 95% CI, −0.03 to 0.14 mmol/L; p = .214). These data suggest that exercise training may have beneficial effects on CRP and other cardiovascular risk factors in postmenopausal breast cancer survivors. Larger randomized controlled trials are warranted.

Introduction

Recent data from the National Cancer Institute Surveillance, Epidemiology, and End Results program suggest that approximately 20% of postmenopausal breast cancer survivors die from cardiovascular disease (Yancik et al., 2001). Independent cardiovascular risk factors include C-reactive protein (CRP)1 (Ridker et al., 2002), resting heart rate (Benetos et al., 1999, Gillman et al., 1993, Greenland et al., 1999, Mensink and Hoffmeister, 1997), heart rate reserve (Cheng et al., 2002), blood pressure (Chobanian et al., 2003, Lewington et al., 2002, Vasan et al., 2002), and lipid profiles (Annon, 1993, Fuster et al., 1996, Ridker et al., 2002). Observational data suggest inverse associations between physical activity and CRP (Abramson and Vaccarino, 2002, Church et al., 2002, Ford, 2002, Geffken et al., 2001, LaMonte et al., 2002, Manns et al., 2003, Pitsavos et al., 2003, Wannamethee et al., 2002) in adult men and women. Randomized controlled trials have shown that exercise can reduce resting heart rate (Hambrecht et al., 2000, Wood et al., 2001), reduce blood pressure (Whelton et al., 2002), and raise HDL-C and lower LDL-C (Leon and Sanchez, 2001) in adult men and women. To date, however, no study has examined the effects of exercise training on cardiovascular risk factors in postmenopausal breast cancer survivors.

Research examining the effects of exercise training on CRP and other cardiovascular risk factors in postmenopausal breast cancer survivors is novel for several reasons. First, it is unknown whether postmenopausal breast cancer survivors will be willing or able to tolerate an exercise regimen sufficient to change cardiovascular risk factors. Second, it is unknown whether exercise-induced changes in cardiovascular risk factors that are seen in healthy adult men and women are altered by the disease and/or its treatment. Third, most of the data on exercise and CRP in healthy populations comes from observational studies. Few studies have been randomized controlled trials (Hammett et al., 2004).

The rehabilitation exercise for health after breast cancer (REHAB) trial was a randomized controlled trial of exercise training in postmenopausal breast cancer survivors who had completed surgery, radiotherapy, and/or chemotherapy with or without current tamoxifen or anastrozole therapy use. We previously reported statistically and clinically significant changes in peak oxygen consumption and quality of life (Courneya et al., 2003) and insulin-like growth factors and insulin-like growth factor binding proteins (Fairey et al., 2003). We also previously reported statistically significant changes in natural killer cell cytotoxicity but no change in standard hematologic variables, whole blood neutrophil function, the phenotypes of isolated mononuclear cells, estimations of unstimulated and phytohemaglutinin-stimulated mononuclear cell function, and the production of pro-inflammatory and anti-inflammatory cytokines (Fairey et al., 2005). Here, we report the effects of exercise training on CRP and other traditional cardiovascular risk factors. We hypothesized that exercise training would have a beneficial effect on CRP.

Section snippets

Methods

The trial design and conduct have been previously described (Courneya et al., 2003). In brief, the study was conducted at the Cross Cancer Institute (CCI) and University of Alberta in Edmonton, Canada. The Alberta Cancer Board and the University of Alberta approved the study. Written informed consent was obtained for all procedures.

Flow of participants through the trial

Flow of participants through the trial has been described (Courneya et al., 2003). In brief, 370 breast cancer survivors were assessed for eligibility and 323 were approved for contact by their physician (37 excluded because physician did not reply to request to contact survivor, 10 excluded because physician denied request to contact survivor). Ninety-one of 323 breast cancer survivors responded to a recruitment letter (225 excluded because they did not reply to recruitment letter, 7 excluded

Discussion

The REHAB trial is the first randomized controlled trial to examine the effects of exercise training on cardiovascular risk factors in postmenopausal breast cancer survivors. We found that exercise training had a borderline statistically significant effect on CRP. In addition, we found that exercise training had a clinically and statistically significant effect on HRR and clinically but not statistically significant effects on RHR, SBP, DBP, HDL-C, and TG.

Our trial had strengths and

Acknowledgments

A Research Team Grant from the National Cancer Institute of Canada (NCIC) funded this study with funds from the Canadian Cancer Society (CCS) and the CCS/NCIC Sociobehavioral Cancer Research Network. The Canada Research Chairs Program supports Kerry Courneya.

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