Exercise and Cancer

In a 2018 assessment, researchers discovered that approximately 80% of the American population is insufficiently active according to guidelines established by HHS. Although the proportion of men and women engaging in regular aerobic and strength training has risen since 2009, these data indicate a continued need for initiatives that facilitate more frequent physical activity.(1) Scientific research has long established the benefits of routine physical exercise, which represents one of the most important modifiable factors conferring protection against cardiovascular disease.(2) Beyond lowering blood pressure, LDL cholesterol, and weight, resistance training builds muscle and improves the functionality of the vasculature. These physiological benefits, which particularly manifest in the arterial wall, accrue over time and may positively modify atherosclerotic plaque formation.(3) Continued research in this field has also revealed that physical activity strengthens the bones and minimizes the risk of fall-related injuries among older adults.(4) Psychologically, perks from exercise appear equally profound across many investigations.

Physical exertion can promote both transient and long-lasting gains in cognition. Such gains appear to be partially mediated by brain-derived neurotrophic factor (BDNF): a neuropeptide widely expressed throughout the central nervous system. While researchers continue to elucidate the role of BDNF, results from previous studies have established its role in promoting hippocampal neurogenesis.(5) Exercise-induced epigenetic changes also very likely influence positive changes in signaling cascades involved in learning, memory, and mood.(6) In a randomized trial, researchers observed a dose-response relationship between exercise and depression; participants assigned to high-dose aerobic exercise experienced a 47% reduction in depression as measured by the Hamilton Rating Scale for Depression. Those assigned to the lower-dose exercise regimen, in contrast, enjoyed a 30% reduction in depression scores.(7) One estimate suggests that regular exercise extends life expectancy by roughly 4 years.(8)

Although research has established that the benefits of physical activity extend to cancer patients, awareness of this key fact appears limited. In a 2017 survey of oncology care providers (n=120), 80% of respondents reported unawareness of exercise guidelines for cancer patients. Additionally, they noted having poor knowledge of how and when to refer certain patients for tailored exercise regimens.(9) Reticence to recommend exercise in certain cancer patient populations (i.e. breast cancer) may stem from an older, unsubstantiated belief that upper body exercise can exacerbate lymphedema, seen in around 20% of treated breast cancer patients.(10)(11) Results from more recent randomized controlled trials appear to invalidate this fear, with researchers noting no significant association between exercise and lymphedema-related symptoms.(12) If anything, progressive, resistance-based exercise in one meta-analysis of 9 studies appeared to reduce the risk of breast-cancer related lymphedema.(13) However, large randomized controlled trials are still necessary to see if exercise can reduce the risk of recurrence in breast cancer.(14)

Beyond possibly helping to alleviate lymphedema, exercise may also help patients experiencing fatigue. Adjuvant radiation therapy (RT) greatly cuts the risk of recurrence in breast cancer but can induce a panoply of unpleasant side effects. Among the most common issues arising from RT is fatigue, which researchers estimate affects between 75-77% of women undergoing the procedure.(15) This exhaustion eclipses typical fatigue in its intensity and duration; it escalates the longer RT continues and can persist for upwards of 7 months after RT cessation.(16) Previous guidelines urged rest and abstinence from physical activity to conserve energy, but such a strategy can beget a nasty feedback loop:,(17)(18)

Figure 1: Radiotherapy-induced fatigue can encourage excessive sedentary behavior, which in turn leads to further physical de-conditioning, muscle wasting, and loss of function that begets further fatigue. Diagram adapted from Piraux et al.

More recent research has established that exercise can counteract the characteristic fatigue accompanying adjuvant RT. In a meta-analysis of 9 studies assessing the link between these two entities, investigators observed statistically significant benefits of supervised, aerobic resistance exercise in patients experiencing treatment-related exhaustion. Substantial clinical heterogeneity across studies made it impossible to quantify the effect of individual parameters on alleviating fatigue.(19) That said, it is worth noting that these results corroborate those found from other trials, which showed similar energy level improvements in patients with prostate, rectal, lung, head, and neck cancers. Because each cancer patient’s physical capabilities vary, researchers recommend that clinicians collaborate closely with exercise professionals to devise tailored workout routines.(18)

Implementing a regular physical routine for cancer patients is particularly critical in women, who are also more susceptible to osteoporosis. Tumor secretions, coupled with associated cancer treatments, can accelerate osteoclast activity and increase bone resorption.(20) Cancer-mediated bone loss can further compound natural losses from menopause, which on its own significantly elevates the risk of fractures.(21) To mitigate the risk of skeletal failure, women recovering from cancer therapies should specifically engage in weight-bearing exercises. In another meta-analysis, researchers noted that women participating in exercise interventions not only maintained bone mass but increased bone mineral density at an average age of 60 years.(22) Although a non-exercising comparison group represents a significant limitation of the study, the results provide another possible reason for clinicians to prescribe an exercise regimen for recovering cancer patients. As research continues in this field, it is a near certainty that the associated benefits of exercise for recovering cancer patients will continue to grow.

Although the effects of exercise on the brain, bones, and cardiovascular system are important in the cancer setting, the most beneficial change is arguably to metabolism. Our muscular system is the largest organ by weight and percentage in the body and therefore acts as the primary consumer of nutrient substrates.(23) When our muscles are active, they require a continuous supply of glucose and amino acids. Muscles take up glucose passively without insulin stimulation at rest and greatly increase the rate of uptake for energy utilization during exercise and activity.(24) Additionally, muscles take up amino acids for rebuilding muscle cells passively and on demand from muscle activation during resistance exercise.(25) Monosaccharides like glucose and fructose are the primary energy substrates in cancer cell metabolism, and results from many studies show cancer cells have an ability to co-opt the use of some amino acids as well (e.g., glutamine).(26) Muscle activation through general or aerobic exercise and more targeted resistance type exercise can conveniently serve as an “overflow valve” when individuals consume excess carbohydrates or proteins. Routine exercise - keeping the muscles “hungry” - coupled with targeted aerobic and resistance training within 30 to 60 minutes before or after a meal could prove a handy tool for cancer patients to complement other metabolic strategies. Clinical trials with cancer patients will provide greater clarity on effect size, but given all the benefits already established, it is difficult to exclude some form of exercise into a comprehensive cancer treatment program.

I frequently remind patients that a “body in motion stays in motion” and that the converse is often frequently true. I also encourage them to find some simple measure or metric of their activity and verify daily or weekly that they are getting stronger rather than weaker. In my experience, cancer patients who observe maintenance or improvement in their physical capacity during cancer treatment and thereafter enjoy a tremendous psychological boost. This positive, liberating impact may have cascading benefits as well on cortisol levels, sympathetic nervous system tone, and other factors that play out under the surface that ultimately impact the outcome of our cancer treatment programs. In a binary sense, “if you’re not getting stronger, you’re getting weaker” and electing for the former must be a priority as a patient embarks on a cancer treatment program.

Stay strong and keep smiling and be your own best doctor,

- Chuck

Charles J. Meakin MD, MHA, MS

Disclaimer: This information is not meant as direct medical advice. Readers should always review options with their local medical team. This is the sole opinion of Dr. Meakin based on a literature review at the time of the blog and may change as new evidence evolves.

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