An informal review of literature on exercise and cancer was undertaken in order to examine the role of exercise in cancer prevention, treatment, rehabilitation, and late survivorship. Population-wide studies show that cancer incidence decreases with increasing physical activity levels. Exercise can decrease the side effects of anticancer therapy, and can aid in recovery and rehabilitation following chemotherapy, radiation, and surgery. Observational studies of breast, colon, and prostate cancer survivors show robust associations between postdiagnosis exercise and decreased cancer-specific mortality. In addition, all-cause mortality in cancer survivors decreases with increasing amounts of exercise. The amount and intensity of exercise required to measure a survival benefit appear to vary by primary tumor type. Decreased breast cancer mortality is seen with the equivalent of 3 hours of walking per week, and decreased colon cancer mortality with 6 hours of walking per week. For these tumors, more vigorous exercise may not improve survival. However, after a prostate cancer diagnosis, more intense exercise is associated with superior survival when compared with walking. The mechanisms behind these differences remain to be elucidated. Further research is also needed to determine the various amounts and intensities of exercise required for optimum cancer prevention, recovery, and survival.
Introduction
“Lack of activity destroys the good condition of every human being, while movement and methodical physical exercise save it and preserve it” — Plato (427–347 BC)
Physical activity intersects with oncology in both the pre-diagnosis and survivorship settings. That physical activity plays a role in the prevention of many cancers is well known, as is the role of exercise in decreasing treatment side effects, speeding recovery after a cancer diagnosis, and enhancing survival. This article will review these intersections of exercise and oncology, discuss the known mechanisms by which exercise exerts its salutary effects, and touch upon the future directions of exercise research in the oncology setting. Finally, recommendations are provided for clinicians to help patients with and without cancer take advantage of the benefits of physical activity.
Regular Exercise Is Associated With Decreased Cancer Risk
That exercise decreases cancer risk is well known, as many studies document the population-wide inverse association between physical activity and cancer incidence. Epidemiologic data from 73 studies conducted around the world, for example, indicate a 25% reduction in the risk of breast cancer among the most physically active women compared with those who are least active.[1] A recent meta-analysis of 19 studies documents the inverse association between kidney cancer and physical activity.[2] Similarly, numerous studies have established the protective role exercise plays in decreasing the risk of many other cancers, including lung, endometrial, colon, and possibly prostate cancer.[3-6]
Regular Exercise May Not Protect Against Health Risks Associated With Prolonged Daily Sitting
However, the dangers of inactivity are especially problematic among those who are consistently sedentary. The possibility that spending more than 4 hours a day behind a desk or working at a computer increases the risk of many chronic diseases, including cancer, has recently gained attention.[7,8]
The extent of the association between sitting and cancer is not fully known. However, current studies, suggesting that regular exercise may not ameliorate the deleterious effects of prolonged sitting,[9] raise concern. That is, an office worker who exercises daily may still incur an increased risk of cancer simply by sitting for more than 4 hours every day.
A timer can be used to remind persons whose job requires prolonged sitting to rise at least once an hour. Suggested activities include climbing a flight or two of stairs, stretching, calisthenics, or taking a short walk. Some office workers make a habit of taking all phone calls standing up. In addition, if the workplace permits, treadmill desks are available from various manufacturers, or a simple one can be constructed in a home shop. Treadmill desks allow reading, writing, or working on a computer while walking very slowly, typically at the rate of 1 mile per hour.
Physical Activity During Cancer Therapy Decreases Treatment Side Effects
In the middle years of the last century, exercise was not recognized as an important part of cancer treatment. The prevailing notion at the time was that cancer patients undergoing cytotoxic treatments should avoid exertion. However, a 1989 randomized trial of 45 women undergoing adjuvant chemotherapy for stage II breast cancer demonstrated that 10 weeks of interval-based, aerobic exercise not only improved functional capacity and body composition, but it also decreased chemotherapy-induced nausea. This pioneering work demonstrated that aerobic exercise was feasible, safe, and beneficial for patients undergoing chemotherapy. [10-12]
Studies since then have carefully documented the positive effects of exercise on patients undergoing chemotherapy or radiation therapy for many different types of cancer.[13-15] At least one study shows that this decrease in symptom burden extends to elderly patients who exercise while in treatment, including improved self-reported health during and after treatment, less memory loss and shortness of breath during treatment, and less fatigue following completion of treatment.[16]
Exercise has also been shown to ameliorate the sexual dysfunction of men undergoing androgen deprivation therapy for advanced prostate cancer.[17] Fifty-seven men on androgen suppression therapy for prostate cancer were randomized to an exercise group or a sedentary control group. The exercise intervention consisted of supervised aerobic activity and resistance training. After 12 weeks of exercising twice weekly, men in the intervention group reported increased sexual interest and activity. In contrast, sexual interest and activity decreased over the same period among men in the control group.
High-Intensity Activity Provides More Benefits Than Light Activity
A recent Cochrane database systematic review of 56 trials encompassing 4,800 subjects found that compared with light exercise, moderate-intensity or vigorous exertion during cancer treatment provided greater improvements in health-related quality of life, physical functioning, anxiety, fatigue, and sleep disturbances.[18]
This suggests that for patients on chemotherapy or radiation, and without contraindications to vigorous exercise, even more benefits will accrue with high-intensity activity. In this Cochrane review, mild exercise was defined as a level of activity that raised the heart rate to 30% to 54% of maximum. Examples of low-intensity activities include walking at a rate of 2 to 3 miles per hour or bicycling at 10 miles per hour. Moderate exercise was defined as activity carried out at 55% to 70% of maximum heart rate. Walking at 3 miles per hour or bicycling at 10 to 20 miles per hour are examples of moderate-intensity activity. Finally, vigorous exercise was defined as that requiring 71% to 95% of maximum heart rate. Running at 5 miles per hour or faster, or bicycling at a speed greater than 20 miles per hour would be considered vigorous activity.
Exercise in the Early Survivorship Stage
Exercise plays a major role in the recovery of function following treatment, and in reducing the lingering effects of both the disease and its treatment. A Canadian systematic review and meta-analysis of 14 randomized controlled trials reporting the effects of exercise on 717 breast cancer survivors 35 to 72 years of age showed that exercise consistently increased cardiorespiratory fitness and quality of life, and, less consistently, decreased fatigue.[19]
As in the treatment phase, the optimal type and frequency of exercise that will most enhance recovery in the early-survivorship stage of cancer is unknown. What is becoming clear, however, is that low-intensity exercise typically provides little relief from insulin resistance, adiposity, and excessive inflammation, all of which are considered pertinent to the progression of many common cancers.
In the RESTORE trial, 82 women enrolled within 4 to 12 weeks of surgery for early-stage breast cancer were randomized to exercise plus lymphedema education or to lymphedema education only. The exercise program consisted of 30 minutes of moderate walking, 20 minutes of upper and lower body strength training, and 10 minutes of stretching, all done twice a week for 18 months. Adherence through the 18-month period was 79%. Although a significant improvement in the
6-Minute Walk Test was reported in the exercise group, no benefit was seen in other parameters, such as quality of life.[20]
This study and other studies demonstrate that not all exercise is equally beneficial for cancer survivors, and that physicians still have little to guide them when deciding how to prescribe exercise for a particular patient.
The authors of the Canadian meta-analysis described above note “the wide variability in study interventions,” and conclude that “the diversity in exercise prescription is not surprising, given the lack of consensus on the optimal exercise prescription for this patient population.”[19] In the 14 studies comprising the Canadian review, the exercise modalities ranged from walking to weight lifting, stationary cycling, tai chi, and jogging, highlighting the need for more orderly assessment of exercise modalities in future research.
In addition, optimal timing of exercise in relation to the cancer-survivorship spectrum may be important. For example, in the same Canadian meta-analysis of exercise studies in breast cancer survivors, the two studies demonstrating an improvement in fatigue were conducted in the post-treatment period. The six studies done in the adjuvant setting found no reduction in fatigue with exercise.
To address these issues, studies are underway to determine the effects of various exercise schedules and modalities on metabolism and fitness.[21]
Finally, patients in the early-survivorship stage often have specific rehabilitation needs related to surgery, radiation, chemotherapy, or the cancer itself. Lymph node dissection and/or axillary radiation can lead to lymphedema of the arm in breast cancer survivors, and this may interfere with exercise enjoyment. Life-saving chemotherapy drugs can leave survivors with peripheral neuropathy. The resulting pain and numbness can affect both the ability and the desire to exercise in previously enjoyable ways. Patients who require limb-sparing surgery for sarcoma treatment may require occupational and physical therapy. Referral to a rehabilitation specialist is appropriate for these patients.
REFERENCES
1. Lynch BM, Neilson HK, Friedenreich CM. Physical activity and breast cancer prevention. Recent Results Cancer Res. 2011;186:13-42.
2. Behrens G Leitzmann MF. The association between physical activity and renal cancer: systematic review and meta-analysis. Br J Cancer. 2013;108:798-811.
3. Boyle T, Keegel T, Bull F, et al. Physical activity and risks of proximal and distal colon cancers: a systematic review and meta-analysis. J Natl Cancer Inst. 2012;104:1548-61.
4. Sun JY, Shi L, Gao XD, Xu SF. Physical activity and risk of lung cancer: a meta-analysis of prospective cohort studies. Asian Pac J Cancer Prev. 2012;13:3143-7.
5. Voskuil DW, Monninkhof EM, Elias SG, et al. Physical activity and endometrial cancer risk, a systematic review of current evidence. Cancer Epidemiol Biomarkers Prev. 2007;16:639-48.
6. Liu Y, Hu F, Li D, et al. Does physical activity reduce the risk of prostate cancer? A systematic review and meta-analysis. Eur Urol. 2011;60:1029-44.
7. Simons CC, Hughes LA, van Engeland M, et al. Physical activity, occupational sitting time, and colorectal cancer risk in the Netherlands cohort study. Am J Epidemiol. 2013;177:514-30.
8. Katzmarzyk PT, Church TS, Craig CL, Bouchard C. Sitting time and mortality from all causes, cardiovascular disease, and cancer. Med Sci Sports Exerc. 2009;41:998-1005.
9. George ES, Rosenkranz RR, Kolt GS. Chronic disease and sitting time in middle-aged Australian males: findings from the 45 and Up Study. Int J Behav Nutr Phys Act. 2013;10:20.
10. MacVicar MG, Winningham ML, Nickel JL. Effects of aerobic interval training on cancer patients' functional capacity. Nurs Res. 1989;38:348-51.
11. Winningham ML, MacVicar MG. The effect of aerobic exercise on patient reports of nausea. Oncol Nurs Forum. 1988;15:447-50.
12. Winningham ML, MacVicar MG, Bondoc M, et al. Effect of aerobic exercise on body weight and composition in patients with breast cancer on adjuvant chemotherapy. Oncol Nurs Forum. 1989;16:683-9.
13. Courneya KS, Sellar CM, Stevinson C, et al. Randomized controlled trial of the effects of aerobic exercise on physical functioning and quality of life in lymphoma patients. J Clin Oncol. 2009;27:4605-12.
14. Courneya KS, Friedenreich CM, Quinney HA, et al. A randomized trial of exercise and quality of life in colorectal cancer survivors. Eur J Cancer Care (Engl). 2003;12:347-57.
15. Mustian KM, Griggs JJ, Morrow GR, et al. Exercise and side effects among 749 patients during and after treatment for cancer: a University of Rochester Cancer Center Community Clinical Oncology Program Study. Support Care Cancer. 2006;14:732-41.
16. Sprod LK, Mohile SG, Demark-Wahnefried W, et al. Exercise and Cancer Treatment Symptoms in 408 Newly Diagnosed Older Cancer Patients. J Geriatr Oncol. 2012;3:90-97.
17. Cormie P, Newton RU, Taaffe DR, et al. Exercise maintains sexual activity in men undergoing androgen suppression for prostate cancer: a randomized controlled trial. Prostate Cancer Prostatic Dis. 2013 Jan 15. [Epub ahead of print]
18. Mishra SI, Scherer RW, Snyder C, et al. Exercise interventions on health-related quality of life for people with cancer during active treatment. Cochrane Database Syst Rev. 2012;8:CD008465.
19. McNeely ML, Campbell KL, Rowe BH, et al. Effects of exercise on breast cancer patients and survivors: a systematic review and meta-analysis. CMAJ. 2006;175:34-41.
20. Anderson RT, Kimmick GG, McCoy TP, et al. A randomized trial of exercise on well-being and function following breast cancer surgery: the RESTORE trial. J Cancer Surviv. 2012;6:172-81.
21. Jones LW, Eves ND, Kraus WE, et al. The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design. BMC Cancer. 2010;10:155.
22. Albrecht TA, Taylor AG. Physical activity in patients with advanced-stage cancer: a systematic review of the literature. Clin J Oncol Nurs. 2012;16:293-300.
23. Meyerhardt JA, Heseltine D, Niedzwiecki D, et al. Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB 89803. J Clin Oncol. 2006;24:3535-41.
24. Meyerhardt JA, Giovannucci EL, Holmes MD, et al. Physical activity and survival after colorectal cancer diagnosis. J Clin Oncol. 2006;24:3527-34.
25. Holmes MD, Chen WY, Feskanich D, et al. Physical activity and survival after breast cancer diagnosis. JAMA. 2005;293:2479-86.
26. Irwin ML, McTiernan A, Manson JE, et al. Physical activity and survival in postmenopausal women with breast cancer: results from the women's health initiative. Cancer Prev Res (Phila). 2011;4:522-9.
27. Kenfield SA, Stampfer MJ, Giovannucci E, Chan JM. Physical activity and survival after prostate cancer diagnosis in the health professionals follow-up study. J Clin Oncol. 2011;29:726-32.
28. Davies NJ, Batehup L, Thomas R. The role of diet and physical activity in breast, colorectal, and prostate cancer survivorship: a review of the literature. Br J Cancer. 2011;105(Suppl 1):S52-73.
29. Schmitz KH, Courneya KS, Matthews C, et al. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc. 2010;42:1409-26.
30. Ballard-Barbash R, Friedenreich CM, Courneya KS, et al. Physical activity, biomarkers, and disease outcomes in cancer survivors: a systematic review. J Natl Cancer Inst. 2012;104:815-40.
31. Fairey AS, Courneya KS, Field CJ, et al. Effects of exercise training on fasting insulin, insulin resistance, insulin-like growth factors, and insulin-like growth factor binding proteins in postmenopausal breast cancer survivors: a randomized controlled trial. Cancer Epidemiol Biomarkers Prev. 2003;12:721-7.
32. Pasanisi P, Berrino F, De Petris M, et al. Metabolic syndrome as a prognostic factor for breast cancer recurrences. Int J Cancer. 2006;119:236-8.
33. Goodwin PJ, Ennis M, Pritchard KI, et al. Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol. 2002;20:42-51.
34. Kroenke CH, Chen WY, Rosner B, Holmes MD. Weight, weight gain, and survival after breast cancer diagnosis. J Clin Oncol. 2005;23:1370-8.
35. Tjonna AE, Lee SJ, Rognmo O, et al. Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome: a pilot study. Circulation. 2008;118:346-54.
36. Laskowski ER. The role of exercise in the treatment of obesity. PM R. 2012;4:840-4.
37. Wisloff U, Stoylen A, Loennechen JP, et al. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation. 2007;115:3086-94.
38. Trapp EG, Chisholm DJ, Freund J, Boutcher SH. The effects of high-intensity intermittent exercise training on fat loss and fasting insulin levels of young women. Int J Obes (Lond). 2008;32:684-91.
39. DiPietro L, Dziura J, Yeckel CW, Neufer PD. Exercise and improved insulin sensitivity in older women: evidence of the enduring benefits of higher intensity training. J Appl Physiol. 2006;100:142-9.
40. Stensvold D, Slordahl SA, Wisloff U. Effect of exercise training on inflammation status among people with metabolic syndrome. Metab Syndr Relat Disord. 2012;10:267-72.
41. Mathivanan S, Ji H, Simpson RJ. Exosomes: extracellular organelles important in intercellular communication. J Proteomics. 2010;73:1907-20.
42. Bartlett JD, Close GL, MacLaren DP, et al. High-intensity interval running is perceived to be more enjoyable than moderate-intensity continuous exercise: implications for exercise adherence. J Sports Sci. 2011;29:547-53.
43. Guiraud T, Nigam A, Juneau M, et al. Acute responses to high-intensity intermittent exercise in CHD Patients. Med Sci Sports Exerc. 2011;43:211-7.
44. Xie L, Jiang Y, Ouyang P, et al. Effects of dietary calorie restriction or exercise on the PI3K and Ras signaling pathways in the skin of mice. J Biol Chem. 2007;282:28025-35.
45. Jones LW, Antonelli J, Masko EM, et al. Exercise modulation of the host-tumor interaction in an orthotopic model of murine prostate cancer. J Appl Physiol. 2012;113:263-72.
46. Kalaany NY, Sabatini DM. Tumours with PI3K activation are resistant to dietary restriction. Nature. 2009;458:725-31.
47. Sigal RJ, Kenny GP, Boule NG, et al. Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial. Ann Intern Med. 2007;147:357-69.
48. Jones LW, Douglas PS, Eves ND, et al. Rationale and design of the Exercise Intensity Trial (EXCITE): a randomized trial comparing the effects of moderate versus moderate to high-intensity aerobic training in women with operable breast cancer. BMC Cancer. 2010;10:531.
49. Memorial Sloan-Kettering Cancer Center: Integrative medicine: our research. Available from: http://www.mskcc.org/cancer-care/integrative-medicine/research.
50. Dallal CM, Brinton LA, Matthews CE, et al. Accelerometer-based measures of active and sedentary behavior in relation to breast cancer risk. Breast Cancer Res Treat. 2012;134:1279-90.
51. Friedenreich C, Norat T, Steindorf K, et al. Physical activity and risk of colon and rectal cancers: the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev. 2006;15:2398-407.
52. Singh AA, Jones LW, Antonelli JA, et al. Association between exercise and primary incidence of prostate cancer: Does race matter? Cancer. 2013;119:1338-43.
53. Richman EL, Kenfield SA, Stampfer MJ, et al. Physical activity after diagnosis and risk of prostate cancer progression: data from the cancer of the prostate strategic urologic research endeavor. Cancer Res. 2011;71:3889-95.
