Physical Activity Reduces the Risk of Recurrence and Mortality in Cancer Patients

Justin C. Brown; L. Anne Gilmore

Disclosures

Exerc Sport Sci Rev. 2020;48(2):67-73. 

In This Article

Abstract and Introduction

Abstract

The biological mechanisms through which physical activity reduces metastatic disease recurrence and mortality in cancer patients are not known. This review offers the hypothesis that physical activity reduces the risk of recurrence and mortality in cancer patients through two synergistic processes: 1) indirect (systemic) effects related to the host tumor microenvironment; and 2) direct (physical) effects on cancer cells.

Introduction

Despite having no evidence of distant metastases at diagnosis, a substantial proportion of patients with cancer will develop metastatic disease recurrence within 5 yr of tumor resection.[1] Metastatic (e.g., systemic) disease recurrence marks the transition from localized, potentially curable to disseminated, often incurable disease that accounts for 90% cancer deaths.[2] An unmet clinical need exists to identify additional therapeutic strategies that can reduce the risk of systemic recurrence and mortality in this population.

The prescription of physical activity is a potential therapeutic strategy to reduce the risk of systemic recurrence and mortality in this population. Physical activity is defined as any bodily movement produced by skeletal muscle that requires energy expenditure.[3] Observational prospective cohort studies report that physical activity is associated with a lower risk of systemic recurrence and mortality in patients diagnosed with several types of cancer. For example, among 2987 women with stage I–III breast cancer, participation in physical activity after diagnosis was associated with a 24% reduction in disease recurrence and 45% reduction in mortality.[4] Among 832 men and women with stage III colon cancer, participation in physical activity was associated with a 40% reduction in disease recurrence and 63% reduction in mortality.[5] Importantly, these associations were independent of various demographic-, clinical-, pathological-, and treatment-related prognostic or confounding factors.

Despite the strength and consistency of these observational data, the biological mechanisms through which physical activity (or exercise) reduces the risk of systemic recurrence and mortality are not yet known. Prevailing hypotheses contend that the benefits of physical activity are attributable to systemic adaptations that occur within the host microenvironment, such as favorable changes in metabolic growth factors, inflammation, and immune function.[6] These changes create a host tumor microenvironment that is insufficient for metastatic initiation and progression. However, mechanical forces also are implicated in metastatic initiation and progression.[7] Microfluidic studies demonstrate that fluid shear stress, similar to that of vascular blood flood, directly affect cell viability, alter intracellular characteristics, retard growth rates, and attenuate the metastatic potential of circulating tumor cells.[8,9] Recently, a proof-of-concept study demonstrated that physical activity reduced circulating tumor cells in patients with resected stage I–III colon cancer.[10] Collectively, these findings offer the rationale that physical activity also may have an effect on cancer cells through a direct physical mechanism, such as shear stress in the vasculature.

In this review, we propose a hypothesis that unifies historic research with contemporary discoveries. We explore the hypothesis that physical activity reduces the risk of systemic recurrence and mortality in cancer patients through two synergistic processes: 1) indirect (systemic) effects in the host tumor microenvironment and 2) direct (physical) effects on cancer cells. The majority of research conducted in this area has included patients with breast and colorectal cancer; however, we describe how this hypothesis may be applicable to other solid tumors. Elucidating the mechanisms through which physical activity reduces the risk of systemic recurrence and mortality is one of the most provocative unanswered questions in oncology. This review provides a rationale that will expand our thinking, foster constructive dialogue, and offer a stimulating premise on which to design future research to elucidate the biological mechanisms that link physical activity with cancer outcomes.

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