Fitness: Can Exercise Lengthen Survival in Patients With Cancer?


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Barrie R. Cassileth, MS, PhD

In light of the apparent survival benefit and the many other positive effects of exercise—such as improved physical function, quality of life, and psychological well being—it is advisable for cancer survivors to meet the recommended 2.5 hours per week of moderate exercise to the extent that their physical condition allows.

—Barrie R. Cassileth, MS, PhD, Ian Yarrett, and Dawn Lemanne, MD, MPH
Integrative Oncology is guest edited by Barrie R. Cassileth, MS, PhD, of Memorial Sloan ­Kettering Cancer Center, New York.

Regular physical activity has long been associated with decreased risk of disease, including many types of cancer. Such benefits may translate into increased life expectancy of up to 4.5 years, with even the lowest levels of activity providing some survival advantage.1 Most strikingly, however, evidence from the past several years suggests that physical activity is not only safe in patients already diagnosed with cancer, but also that it may decrease the risk of recurrence and extend survival. This overview presents a summary of the research to date and its clinical implications for cancer care providers.

The effects of postdiagnosis physical activity on cancer recurrence and survival have been examined in over 20 observational studies but in few randomized controlled trials.2 Existing studies have focused primarily on breast, colorectal, prostate, and ovarian cancer survivors. They generally describe an inverse relationship between the level of postdiagnosis physical activity and risk of cancer recurrence and/or mortality, with the strongest evidence found in patients with breast and colorectal cancers. 

Breast Cancer

Research suggests that patients with breast cancer who engage in moderate physical activity at various levels have a significantly lower risk of cancer-specific and/or all-cause mortality. The safety of physical activity in breast cancer survivors, even during treatment, has been documented in numerous trials.2 

One prospective observational study of 933 women with local or regional breast cancer found that any moderate-intensity exercise after diagnosis, such as brisk walking, reduced mortality risk by 64% compared to inactive women.3 Exercise of the same intensity for 2.5 hr/wk—the level recommended for the general population by the U.S. Department of Health and Human Services4—was associated with a mortality reduction of 67% compared to inactive women.3

Generally, a decreased risk of 40% to 67% was observed across studies.3,5,6 A meta-analysis of six studies, covering 12,108 patients, found that postdiagnosis exercise was associated with a 34% lower risk of breast cancer–related deaths, a 41% lower risk of all-cause mortality, and a 24% lower risk of breast cancer recurrence.7

Colorectal Cancer

Several large cohort studies in colorectal cancer survivors document similar survival advantages and reduced recurrence risk in patients who engaged in physical activity after diagnosis, with improvements of up to 50%.8-11 Based on the promise of these findings, a phase III randomized controlled trial called the Colon Health and Life-Long Exercise Change trial (CHALLENGE) is now underway to assess the effects of a 3-year physical activity program on clinical outcomes in stage II and III colon cancer survivors who have completed chemotherapy.12 (The study has an estimated completion date of December 2030.)

Mechanisms Underlying the Survival Benefits

Despite evidence that physical activity may extend survival, the specific biologic mechanisms that underlie this benefit remain unclear. With regard to breast cancer, exercise is postulated to affect survival by decreasing body fat, insulin resistance, sex hormone levels, and inflammation, all of which would be expected to improve cancer-specific survival.13 Women who are overweight, obese, or have high fasting insulin levels at the time of diagnosis, or who gain weight after diagnosis, tend to have poorer outcomes.14-16 Thus, weight loss facilitated by physical activity may improve cancer-specific survival.

A study published in JAMA in 2005 found that the amount of exercise was associated with increased survival in a dose-dependent fashion. These investigators also noted that the survival advantage from physical activity was greater for women with estrogen receptor–positive tumors.6 Because drugs that decrease estrogen activity, such as tamoxifen and aromatase inhibitors, help treat hormone-sensitive tumors, exercise-induced decreases in sex hormone signaling might have similar benefits.

Exercise also may modulate inflammatory signaling, which in turn is postulated to have a role in tumor angiogenesis and metastasis. A study in mice using human breast cancer xenografts demonstrated that increased inflammatory signaling in tumor-associated endothelial tissue accelerated tumor growth and, further, that disruption of this signaling impaired growth.17

Moderate-Intensity vs High-Intensity Exercise

Exercise research in patients with cancer has focused on moderate-intensity exercise, which requires exertion at 60% to 75% of maximal effort. High-intensity aerobic exercise, however, which involves 10- to 30-second sprints at or near maximal effort, may reduce body fat, improve insulin resistance, and modulate inflammation more quickly and effectively than moderate exercise.18-21 In addition, high-intensity exercise improves motivation and adherence in participants.22,23 

An ongoing study at Memorial Sloan-Kettering Cancer Center will assess the safety and feasibility of a high-intensity exercise program in patients with breast cancer and compare the effects of high- vs moderate intensity exercise on relevant biomarkers.

Motivating Patients to Exercise

Despite strong evidence supporting the safety and benefits of exercise in cancer survivors, most are not physically active. Studies suggest that fewer than 10% of cancer survivors are physically active during their primary treatments and only 20% to 30% are active after treatment.2 Thus, behavioral support interventions are needed to help patients with cancer experience the benefits of a physically active lifestyle. Short-term supervised exercise, support groups, and telephone counseling are among the strategies that have been successful.2

Concluding Thoughts

Taken together, the available evidence suggests that exercise can help improve cancer-specific survival in patients, although the physiologic mechanisms await documentation. Further research, particularly via randomized controlled trials, is needed to establish the most effective amount, timing, and type of exercise, as well as whether and how they may vary by specific cancer diagnosis. 

In light of the apparent survival benefit and the many other positive effects of exercise—such as improved physical function, quality of life, and psychological well-being—it is advisable for cancer survivors to meet the recommended 2.5 hours per week of moderate exercise to the extent that their physical condition allows. Care must be taken to avoid exercise-related injuries, mitigate the risk of adverse effects, and consider the patient’s physical condition, treatment regimen, etc. Special precautions should be taken for older adults with bone disease, for example. 

Survivor-specific guidelines developed by an expert panel of the American College of Sports Medicine may be a useful resource. It recommends that survivors avoid inactivity and become physically active as soon as possible after diagnosis and/or treatment.24

Disclosure: Drs. Cassileth and Lemanne and Mr. Yarett reported no potential conflicts of interest.

References

1. Moore SC, Patel AV, Matthews CE, et al: Leisure time physical activity of moderate to vigorous intensity and mortality: A large pooled cohort analysis. PLoS Med 9:e1001335, 2012.

2. Rock CL, Doyle C, Demark-Wahnefried W, et al: Nutrition and physical activity guidelines for cancer survivors. CA Cancer J Clin 62:243-274, 2012.

3. Irwin ML, Smith AW, McTiernan A, et al: Influence of pre- and postdiagnosis physical activity on mortality in breast cancer survivors: The health, eating, activity, and lifestyle study. J Clin Oncol 26:3958-3964, 2008.

4. U.S. Department of Health and Human Services: 2008 Physical Activity Guidelines for Americans. Washington, DC, U.S. Department of Health and Human Services, 2008.

5. Holick CN, Newcomb PA, Trentham-Dietz A, et al: Physical activity and survival after diagnosis of invasive breast cancer. Cancer Epidemiol Biomarkers Prev 17:379-386, 2008.

6. Holmes MD, Chen WY, Feskanich D, et al: Physical activity and survival after breast cancer diagnosis. JAMA 293:2479-2486, 2005.

7. Ibrahim EM, Al-Homaidh A: Physical activity and survival after breast cancer diagnosis: Meta-analysis of published studies. Med Oncol 28:753-765, 2011.

8. Meyerhardt JA, Giovannucci EL, Ogino S, et al: Physical activity and male colorectal cancer survival. Arch Intern Med 169:2102-2108, 2009.

9. 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 24:3535-3541, 2006.

10. Meyerhardt JA, Giovannucci EL, Holmes MD, et al: Physical activity and survival after colorectal cancer diagnosis. J Clin Oncol 24:3527-3534, 2006.

11. Haydon AM, Macinnis RJ, English DR, et al: Effect of physical activity and body size on survival after diagnosis with colorectal cancer. Gut 55:62-67, 2006.

12. Courneya KS, Booth CM, Gill S, et al: The Colon Health and Life-Long Exercise Change trial: A randomized trial of the National Cancer Institute of Canada Clinical Trials Group. Curr Oncol 15:279-285, 2008.

13. 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 104:815-840, 2012.

14. 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 20:42-51, 2002.

15. Bradshaw PT, Ibrahim JG, Stevens J, et al: Postdiagnosis change in bodyweight and survival after breast cancer diagnosis. Epidemiology 23:320-327, 2012.

16. Nichols HB, Trentham-Dietz A, Egan KM, et al: Body mass index before and after breast cancer diagnosis: Associations with all-cause, breast cancer, and cardiovascular disease mortality. Cancer Epidemiol Biomarkers Prev 18:1403-1409, 2009.

17. Pitroda SP, Zhou T, Sweis RF, et al: Tumor endothelial inflammation predicts clinical outcome in diverse human cancers. PLoS One 7:e46104, 2012.

18. King AC, Haskell WL, Young DR, et al: Long-term effects of varying intensities and formats of physical activity on participation rates, fitness, and lipoproteins in men and women aged 50 to 65 years. Circulation 91:2596-2604, 1995.

19. Richards JC, Johnson TK, Kuzma JN, et al: Short-term sprint interval training increases insulin sensitivity in healthy adults but does not affect the thermogenic response to beta-adrenergic stimulation. J Physiol 588:2961-2972, 2010.

20. Leggate M, Carter WG, Evans MJ, et al: Determination of inflammatory and prominent proteomic changes in plasma and adipose tissue after high-intensity intermittent training in overweight and obese males. J Appl Physiol 112:1353-1360, 2012.

21. Lee MG, Park KS, Kim DU, et al: Effects of high-intensity exercise training on body composition, abdominal fat loss, and cardiorespiratory fitness in middle-aged Korean females. Appl Physiol Nutr Metab 37:1019-1027, 2012.

22. 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 115:3086-3094, 2007.

23. 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 29:547-553, 2011.

24. Schmitz KH, Courneya KS, Matthews C, et al: American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc 42:1409-1426, 2010.


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