Physical Activity, Biomarkers, and Disease Outcomes in Cancer Survivors

A Systematic Review

Rachel Ballard-Barbash; Christine M. Friedenreich; Kerry S. Courneya; Sameer M. Siddiqi; Anne McTiernan; Catherine M. Alfano

Disclosures

J Natl Cancer Inst. 2012;104(11):815-840. 

In This Article

Abstract and Introduction

Abstract

Background Cancer survivors often seek information about how lifestyle factors, such as physical activity, may influence their prognosis. We systematically reviewed studies that examined relationships between physical activity and mortality (cancer-specific and all-cause) and/or cancer biomarkers.
Methods We identified 45 articles published from January 1950 to August 2011 through MEDLINE database searches that were related to physical activity, cancer survival, and biomarkers potentially relevant to cancer survival. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement to guide this review. Study characteristics, mortality outcomes, and biomarker-relevant and subgroup results were abstracted for each article that met the inclusion criteria (ie, research articles that included participants with a cancer diagnosis, mortality outcomes, and an assessment of physical activity).
Results There was consistent evidence from 27 observational studies that physical activity is associated with reduced all-cause, breast cancer–specific, and colon cancer–specific mortality. There is currently insufficient evidence regarding the association between physical activity and mortality for survivors of other cancers. Randomized controlled trials of exercise that included biomarker endpoints suggest that exercise may result in beneficial changes in the circulating level of insulin, insulin-related pathways, inflammation, and, possibly, immunity; however, the evidence is still preliminary.
Conclusions Future research directions identified include the need for more observational studies on additional types of cancer with larger sample sizes; the need to examine whether the association between physical activity and mortality varies by tumor, clinical, or risk factor characteristics; and the need for research on the biological mechanisms involved in the association between physical activity and survival after a cancer diagnosis. Future randomized controlled trials of exercise with biomarker and cancer-specific disease endpoints, such as recurrence, new primary cancers, and cancer-specific mortality in cancer survivors, are warranted.

Introduction

An estimated 13.8 million cancer survivors were living in the United States as of 2010, and this number is projected to grow to 18.1 million by 2020.[1] With advances in cancer screening and treatment, cancer survivors are living longer and are seeking information about how lifestyle factors, such as physical activity, may influence their prognosis.[2] Evidence of the influence of physical activity on health-related fitness, quality of life, and other patient-reported outcomes among cancer survivors during and after treatment has been reviewed previously.[3–12] In 2010, the American College of Sports Medicine (ACSM) reviewed the research on the safety and efficacy of exercise training during and after adjuvant cancer therapy.[13] That review focused on randomized controlled trial (RCT) evidence, where available, which was extensive for breast and prostate cancers and more limited for colon, hematological, and gynecological cancers, and also included a limited number of prospective cohort studies. Overall, the RCT evidence indicates that exercise training is safe during and after cancer treatment, although the ACSM review did identify some areas of concern for survivor safety with particular types and intensities of exercise for certain survivor groups. The ACSM review found that exercise training resulted in improvements in physical functioning, quality of life, and cancer-related fatigue for a number of cancer survivor groups.[13] In 2008, the US Department of Health and Human Services published physical activity guidelines based primarily on a review of research on physical activity and cancer prevention; that publication included a short review on cancer survivorship based on three studies published before 2007 that focused on late and long-term effects of physical activity.[4] Since the publication of these two reviews, there have been many more studies examining the effects of physical activity in cancer survivors, warranting a more detailed assessment of this evidence.

In addition to the observational research on the effects of physical activity in cancer survivors, several RCTs of exercise interventions and mortality outcomes in cancer survivors have begun or been published. In 2009, the first RCT to investigate the effect of a specific physical activity intervention on overall and disease-free survival among colon cancer survivors was launched in Canada and Australia.[14] In addition, several smaller RCTs have examined the effect of physical activity interventions on a number of biomarkers and mechanistic pathways that may be relevant to cancer prognosis. The purpose of this review was to systematically examine results of in two areas of research involving cancer survivors: physical activity and cancer-specific and all-cause mortality, and physical activity and relevant cancer biomarkers. This systematic review differs from previous reviews, which were broad or focused on health-related fitness outcomes and/or patient-reported outcomes, such as quality of life, fatigue, and cancer-related symptoms,[4,5,8–11,13] examined only one cancer,[6,9,12] addressed cancer prevention in addition to cancer survival,[4,11] or included combined dietary and physical activity interventions.[7] We also summarize the limited number of RCTs that assessed effects of physical activity interventions on biomarkers in cancer patients or survivors to evaluate the extent of evidence on biological mechanisms that may underlie associations between physical activity and cancer prognosis. Finally, we propose priorities for future research in this field.

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