Cancer Causes & Control

, Volume 22, Issue 6, pp 811–826 | Cite as

Physical activity and cancer prevention: a systematic review of clinical trials

  • Brooke M. Winzer
  • David C. Whiteman
  • Marina M. Reeves
  • Jennifer D. Paratz
Review article



Physically active individuals have lower rates of many cancers and improved cancer outcomes. Controlled exercise trials measuring putative biomarkers of cancer risk are being conducted to further understand the role of exercise in cancer etiology and progression. We aimed to systematically review the effect of exercise on various biomarkers.


A comprehensive search strategy identified 353 publications from January 1980 to August 2010. We included those clinical trials of exercise measuring biomarkers following minimum 4-week intervention among cancer survivors or people with one or more cancer risk factors. Two reviewers abstracted data and assessed quality independently. Effect sizes and 95% confidence intervals were estimated.


Four primary prevention and five tertiary prevention trials were included. Exercise had a small to moderate effect on improving concentrations of several blood biomarkers implicated in breast and colon cancer pathways including insulin, leptin, estrogens, and apoptosis regulation. In breast cancer survivors, exercise had a small to moderate effect on improving some biomarkers associated with prognosis including various insulin-like growth factor axis proteins, insulin, and inflammation; and a large effect on enhancing immune function.


Data are few, but there is some evidence to support the role of exercise in modulating various cancer pathways.


Exercise Neoplasms Prevention and control Biologic markers Survival 



BMW is supported by an Australian Postgraduate Award. DCW is a Fellow of the Australian Research Council and MMR is a Training Research Fellow of the National Health and Medical Research Council of Australia.

Conflicts of interest

No potential conflicts of interest were disclosed.


  1. 1.
    Haskell W, Lee I, Pate R, Powell K, Blair S, Franklin BA et al. (2007) Physical activity and public health. Updated recommendation for adults from the American College of Sports Medicine and the American Heart Association CirculationGoogle Scholar
  2. 2.
    Schmitz KH, Courneya KS, Matthews C, Demark-Wahnefried W, Galvao DA, Pinto BM et al (2010) American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sport Exerc 42:1409–1426CrossRefGoogle Scholar
  3. 3.
    World Cancer Research Fund/American Institute for Cancer Research (2007) The second expert report: food, nutrition, physical activity and the prevention of cancer: a global perspective. American Institute for Cancer Research, Washington, DCGoogle Scholar
  4. 4.
    Friedenreich CM, Neilson HK, Lynch BM (2010) State of the epidemiological evidence on physical activity and cancer prevention. Eur J Cancer 46:2593–2604PubMedCrossRefGoogle Scholar
  5. 5.
    Wolin KY, Yan Y, Colditz GA, Lee IM (2009) Physical activity and colon cancer prevention: a meta-analysis. Br J Cancer 100:611–616PubMedCrossRefGoogle Scholar
  6. 6.
    Eliassen AH, Hankinson SE, Rosner B, Holmes MD, Willett WC (2010) Physical activity and risk of breast cancer among postmenopausal women. Arch Intern Med 170:1758–1764PubMedCrossRefGoogle Scholar
  7. 7.
    Friedenreich C, Cust AE (2008) Physical activity and breast cancer risk: impact of timing, type and dose of activity and population subgroup effects. Br J Sports Med 0:1–12Google Scholar
  8. 8.
    Monninkhof E, Elias S, Vlems F, van der Tweel I, Schuit A, Voskuil D et al (2007) Physical activity and breast cancer: a systematic review. Epidemiology 18:137–157PubMedCrossRefGoogle Scholar
  9. 9.
    Voskuil DW, Monninkhof EM, Elias SG, Vlems FA, van Leeuwen FE (2007) Physical activity and endometrial cancer risk, a systematic review of current evidence. Cancer Epidemiol Biomarkers Prev 16:639–648PubMedCrossRefGoogle Scholar
  10. 10.
    Moore SC, Peters TM, Ahn J, Park Y, Schatzkin A, Albanes D et al (2008) Physical activity in relation to total, advanced, and fatal prostate cancer. Cancer Epidemiol Biomarkers Prev 17:2458–2466PubMedCrossRefGoogle Scholar
  11. 11.
    Olsen CM, Bain CJ, Jordan SJ, Nagle CM, AlC Green, Whiteman DC et al (2007) Recreational physical activity and epithelial ovarian cancer: a case–control study, systematic review, and meta-analysis. Cancer Epidemiol Biomarkers Prev 16:2321–2330PubMedCrossRefGoogle Scholar
  12. 12.
    Irwin ML, Smith AW, McTiernan A, Ballard-Barbash R, Cronin K, Gilliland FD et al (2008) Influence of pre- and postdiagnosis physical activity on mortality in breast cancer survivors: the health, eating, activity, and lifestyle study. J Clin Oncol 26:3958–3964PubMedCrossRefGoogle Scholar
  13. 13.
    McTiernan A, Irwin M, VonGruenigen V (2010) Weight, physical activity, diet, and prognosis in breast and gynecologic cancers. J Clin Oncol 28:4074–4080PubMedCrossRefGoogle Scholar
  14. 14.
    Ibrahim E, Al-Homaidh A (2010) Physical activity and survival after breast cancer diagnosis: meta-analysis of published studies. Med Oncol. doi: 10.1007/s12032-010-9536-x:1-13
  15. 15.
    Meyerhardt JA, Giovannucci EL, Ogino S, Kirkner GJ, Chan AT, Willett W et al (2009) Physical activity and male colorectal cancer survival. Arch Intern Med 169:2102–2108PubMedCrossRefGoogle Scholar
  16. 16.
    Kenfield SA, Stampfer MJ, Giovannucci E, Chan JM (2011) Physical activity and survival after prostate cancer diagnosis in the health professionals follow-up study. J Clin Oncol. doi: 10.1200/JCO.2010.31.5226
  17. 17.
    Protani M, Coory M, Martin J (2010) Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat 123:627–635PubMedCrossRefGoogle Scholar
  18. 18.
    Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med 348:1625–1638PubMedCrossRefGoogle Scholar
  19. 19.
    McTiernan A (2008) Mechanisms linking physical activity with cancer. Nat Rev 8:205–211Google Scholar
  20. 20.
    Campbell KL, McTiernan A (2007) Exercise and biomarkers for cancer prevention studies. J Nutr 137:161S–169SPubMedGoogle Scholar
  21. 21.
    McTiernan A, Schwartz RS, Potter J, Bowen D (1999) Exercise clinical trials in cancer prevention research: a call to action. Cancer Epidemiol Biomarkers Prev 8:201–207PubMedGoogle Scholar
  22. 22.
    McTiernan A (2003) Intervention studies in exercise and cancer prevention. Med Sci Sports Exerc 35:1841–1845PubMedCrossRefGoogle Scholar
  23. 23.
    Westerlind KC (2003) Physical activity and cancer prevention-mechanisms. Med Sci Sport Exerc 35:1834–1840CrossRefGoogle Scholar
  24. 24.
    Kaaks R, Lukanova A (2001) Energy balance and cancer: the role of insulin and insulin-like growth factor-I. Proc Nutr Soc 60:91–106PubMedCrossRefGoogle Scholar
  25. 25.
    Nielson HK, Friedenreich C, Brockton NT, Millikan R (2009) Physical activity and postmenopausal breast cancer: proposed biologic mechanisms and areas for future research. Cancer Epidemiol Biomarkers Prev 18:11–27CrossRefGoogle Scholar
  26. 26.
    Wu MH, Chou YC, Chou WY, Hsu GC, Chu CH, Yu CP et al (2009) Circulating levels of leptin, adiposity and breast cancer risk. Br J Cancer 100:578–582PubMedCrossRefGoogle Scholar
  27. 27.
    Harriss DJ, Cable NT, George K, Reilly T, Renehan AG, Haboubi N (2007) Physical activity before and after diagnosis of colorectal cancer—disease risk, clinical outcomes, response pathways and biomarkers. Sports Med 37:947–960PubMedCrossRefGoogle Scholar
  28. 28.
    Kumor A, Daniel P, Pietruczuk M, Malecka-Panas E (2009) Serum leptin, adiponectin, and resistin concentration in colorectal adenoma and carcinoma (CC) patients. Int J Colorectal Dis 24:275–281PubMedCrossRefGoogle Scholar
  29. 29.
    Mistry T, Digby JE, Desai KM, Randeva HS (2007) Obesity and prostate cancer: a role for adipokines. Eur Urol 52:46–53PubMedCrossRefGoogle Scholar
  30. 30.
    Terzidis A, Sergentanis TN, Antonopoulos G, Syrigos C, Efremidis A, Polyzos A et al (2009) Elevated serum leptin levels: a risk factor for non-small-cell lung cancer? Oncology 76:19–25PubMedCrossRefGoogle Scholar
  31. 31.
    Kelesidis I, Kelesidis T, Mantzoros CS (2006) Adiponectin and cancer: a systematic review. Br J Cancer 94:1221–1225PubMedCrossRefGoogle Scholar
  32. 32.
    Kerlikowske K, Cook AJ, Buist DSM, Cummings SR, Vachon C, Vacek P et al (2010) Breast cancer risk by breast density, menopause, and postmenopausal hormone therapy use. J Clin Oncol 28:3830–3837PubMedCrossRefGoogle Scholar
  33. 33.
    Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B et al (1998) Circulating concentrations of insulin-like growth factor I and risk of breast cancer. Lancet 351:1393–1396PubMedCrossRefGoogle Scholar
  34. 34.
    Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Hartwick W et al (2002) Insulin-like growth factor binding proteins 1 and 3 and breast cancer outcomes. Breast Cancer Res Treat 74:65–76PubMedCrossRefGoogle Scholar
  35. 35.
    Giovannucci E (2001) Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr 131:S3109Google Scholar
  36. 36.
    Anti M, Marra G, Armelao F, Percesepe A, Ficarelli R, Ricciuto GM et al (1993) Rectal epithelial cell proliferation patterns as predictors of adenomatous colorectal polyp recurrence. Gut 34:525–530PubMedCrossRefGoogle Scholar
  37. 37.
    Srivastava S, Verma M, Henson D (2001) Biomarkers for early detection of colon cancer. Clin Cancer Res 7:1118–1126PubMedGoogle Scholar
  38. 38.
    Hardman AE (2001) Physical activity and cancer risk. Proc Nutr Soc 60:107–113PubMedCrossRefGoogle Scholar
  39. 39.
    Hong M, Turner N (2005) Differential response to DNA damage may explain different cancer susceptibility between small and large intestine. Exp Biol Med 230:464–471Google Scholar
  40. 40.
    Shephard RJ, Shek PN (1995) Cancer, immune function, and physical activity. Can J Appl Physiol 20:1–25PubMedCrossRefGoogle Scholar
  41. 41.
    Pierce BL, Ballard-Barbash R, Bernstein L, Baumgartner RN, Neuhouser ML, Wener MH et al (2009) Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. J Clin Oncol 27:3437–3444PubMedCrossRefGoogle Scholar
  42. 42.
    van Tulder MW, Assendelft WJJ, Koes BW, Bouter LM (1997) Method guidelines for systematic reviews in the Cochrane collaboration back review group for spinal disorders. Spine 22:2323–2330PubMedCrossRefGoogle Scholar
  43. 43.
    Verhagen AP, De Vet HCW, De Bie RA, Kessels AGH, Boers M, Bouter LM et al (1998) The Delphi list: a criteria list for quality assessment of randomised clinical trials for conducting systematic reviews developed by Delphi consensus. J Clin Epidemiol 51:1235–1241PubMedCrossRefGoogle Scholar
  44. 44.
    Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ et al (2010) CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ 340:c869PubMedCrossRefGoogle Scholar
  45. 45.
    Maher CG, Sherrington C, Herbert RD, Moseley AM et al (2003) Reliability of the PEDro scale for rating quality of randomised controlled trials. Phys Ther 83:713–721PubMedGoogle Scholar
  46. 46.
    Cohen J (1988) Statistical power analysis for the behavioural sciences, 2nd edn. Lawrence Erlbaum Associates, Hillsdale, pp 19–74Google Scholar
  47. 47.
    Nieman DC, Cook VD, Henson DA, Suttles J, Rejeski WJ, Ribisl PM et al (1995) Moderate exercise training and natural killer cell cytotoxic activity in breast cancer patients. Int J Sports Med 16:334–337PubMedCrossRefGoogle Scholar
  48. 48.
    Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097. doi: 10.1371/journal.pmed.1000097 PubMedCrossRefGoogle Scholar
  49. 49.
    Monninkhof EM, Velthuis MJ, Peeters PHM, Twisk JWR, Schuit AJ (2009) Effect of exercise on postmenopausal sex hormone levels and role of body fat: a randomized controlled trial. J Clin Oncol 27:4492–4499PubMedCrossRefGoogle Scholar
  50. 50.
    McTiernan A, Sorensen B, Yasui Y, Tworoger S, Ulrich C, Irwin M et al (2005) No effect of exercise on insulin-like growth factor I and insulin-like growth factor binding protein 3 in postmenopausal women: a 12-month randomized clinical trial. Cancer Epidemiol Biomarkers Prev 14:1020–1021PubMedCrossRefGoogle Scholar
  51. 51.
    McTiernan A, Tworoger S, Rajan K, Yasui Y, Sorensen B, Ulrich C et al (2004) Effect of exercise on serum androgens in postmenopausal women: a 12-month randomized clinical trial. Cancer Epidemiol Biomarkers Prev 13:1099–1105PubMedGoogle Scholar
  52. 52.
    McTiernan A, Tworoger S, Ulrich C, Yasui Y, Irwin M, Rajan K et al (2004) Effect of exercise on serum estrogens in postmenopausal women: a 12-month randomized clinical trial. Cancer Res 64:2923–2928PubMedCrossRefGoogle Scholar
  53. 53.
    Frank L, Sorensen B, Yasui Y, Tworoger S, Schwartz R, Ulrich C et al (2005) Effects of exercise on metabolic risk variables in overweight postmenopausal women: a randomized clinical trial. Obes Res 13:615–625PubMedCrossRefGoogle Scholar
  54. 54.
    Friedenreich CM, Woolcott CG, McTiernan A, Ballard-Barbash R, Brant RF, Stanczyk FZ et al (2010) Alberta physical activity and breast cancer prevention trial: sex hormone changes in a year-long exercise intervention among postmenopausal women. J Clin Oncol 28:1458–1466PubMedCrossRefGoogle Scholar
  55. 55.
    Woolcott CG, Courneya KS, Boyd NF, Yaffe MJ, Terry T, McTiernan A et al (2010) Mammographic density change with 1 year of aerobic exercise among postmenopausal women: a randomized controlled trial. Cancer Epidemiol Biomarkers Prev 19:1112–1121PubMedCrossRefGoogle Scholar
  56. 56.
    McTiernan A, Yasui Y, Sorensen B, Irwin ML, Morgan A, Rudolph RE et al (2006) Effect of a 12-month exercise intervention on patterns of cellular proliferation in colonic crypts: a randomized controlled trial. Cancer Epidemiol Biomarkers Prev 15:1588–1597PubMedCrossRefGoogle Scholar
  57. 57.
    Campbell KL, McTiernan A, Li SS, Sorensen B, Yasui Y, Lampe JW et al (2007) Effect of a 12-month exercise intervention on the apoptotic regulating proteins Bax and Bcl-2 in colon crypts: a randomized controlled trial. Cancer Epidemiol Biomarkers Prev 16:1767–1774PubMedCrossRefGoogle Scholar
  58. 58.
    Abrahamson PE, King IB, Ulrich CM, Rudolph RE, Irwin ML, Yasui Y et al (2007) No effect of exercise on colon mucosal prostaglandin concentrations: a 12-month randomized controlled trial. Cancer Epidemiol Biomarkers Prev 16:2351–2356PubMedCrossRefGoogle Scholar
  59. 59.
    Irwin M, Varma K, Alvarez-Reeves M, Cadmus L, Wiley A, Chung GG et al (2009) Randomized controlled trial of aerobic exercise on insulin and insulin-like growth factors in breast cancer survivors: the Yale exercise and survivorship study. Cancer Epidemiol Biomarkers Prev 18:306–312PubMedCrossRefGoogle Scholar
  60. 60.
    Fairey AS, Courneya KS, Field CJ, Bell GJ, Jones LW, Mackey JR (2003) 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 12:721–727PubMedGoogle Scholar
  61. 61.
    Fairey AS, Courneya KS, Field CJ, Bell GJ, Jones LW, Mackey JR (2005) Randomized controlled trial of exercise and blood immune function in postmenopausal breast cancer survivors. J Appl Physiol 98:1534–1540PubMedCrossRefGoogle Scholar
  62. 62.
    Fairey AS, Courneya KS, Field CJ, Bell GJ, Jones LW, Martin BS et al (2005) Effect of exercise training on C-reactive protein in postmenopausal breast cancer survivors: a randomized controlled trial. Brain Behav Immun 19:381–388PubMedCrossRefGoogle Scholar
  63. 63.
    Schmitz KH, Ahmed RL, Hannan PJ, Yee D (2005) Safety and efficacy of weight training in recent breast cancer survivors to alter body composition, insulin, and insulin-like growth factor axis proteins. Cancer Epidemiol Biomarkers Prev 14:1672–1680PubMedCrossRefGoogle Scholar
  64. 64.
    Ligibel JA, Campbell N, Partridge A, Chen WY, Salinardi T, Chen H et al (2008) Impact of a mixed strength and endurance exercise intervention on insulin levels in breast cancer survivors. J Clin Oncol 26:907–912PubMedCrossRefGoogle Scholar
  65. 65.
    Ligibel JA, Giobbie-Hurder A, Olenczuk D, Campbell N, Salinardi T, Winer EP et al (2009) Impact of a mixed strength and endurance exercise intervention on levels of adiponectin, high molecular weight adiponectin and leptin in breast cancer survivors. Cancer Causes Control 20:1523–1528PubMedCrossRefGoogle Scholar
  66. 66.
    Hutnick NA, Williams NI, Kraemer WJ, Orsega-Smith E, Dixon RH, Bleznak AD et al (2005) Exercise and lymphocyte activation following chemotherapy for breast cancer. Med Sci Sports Exerc 37:1827–1835PubMedCrossRefGoogle Scholar
  67. 67.
    Del Giudice ME, Fantus G, Ezzat S, McKeown-Eyssen G, Page D, Goodwin P (1998) Insulin and related factors in premenopausal breast cancer risk. Breast Cancer Res Treat 47:111–120PubMedCrossRefGoogle Scholar
  68. 68.
    Rennert G, Rennert HS, Pinchev M, Lavie O, Gruber SB (2009) Use of hormone replacement therapy and the risk of colorectal cancer. J Clin Oncol 27:4542–4547PubMedCrossRefGoogle Scholar
  69. 69.
    Lee I (2003) Physical activity and cancer prevention—data from epidemiologic studies. Med Sci Sports Exerc 35:1823–1827PubMedCrossRefGoogle Scholar
  70. 70.
    Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y et al (2002) Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol 20:42–51PubMedCrossRefGoogle Scholar
  71. 71.
    Borghouts LB, Keizer HA (2000) Exercise and insulin sensitivity: a review. Int J Sports Med 21:1–12PubMedCrossRefGoogle Scholar
  72. 72.
    Goodwin PJ (2008) Insulin in the adjuvant breast cancer setting: a novel therapeutic target for lifestyle and pharmacologic interventions? J Clin Oncol 26:833–834PubMedCrossRefGoogle Scholar
  73. 73.
    Lindsay C, Evans T (2008) The insulin-like growth factor system and its receptors: a potential novel anticancer target. Biologics 2:855–864PubMedGoogle Scholar
  74. 74.
    Vadgama JV, Wu Y, Datta G, Khan H, Chillar R (1999) Plasma insulin-like growth factor-I and serum IGF-binding protein 3 can be associated with the progression of breast cancer, and predict the risk of recurrence and the probability of survival in African-American and Hispanic women. Oncology 57:330PubMedCrossRefGoogle Scholar
  75. 75.
    Marana HRC, Silva JS, Andrade JM, Bighetti S (2000) Reduced immunologic cell performance as a prognostic parameter for advanced cervical cancer. Int J Gynecol Cancer 10:67–73PubMedCrossRefGoogle Scholar
  76. 76.
    Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867PubMedCrossRefGoogle Scholar
  77. 77.
    Pedersen BK, Steensberg A, Fischer C, Keller C, Ostrowski K, Schjerling P (2001) Exercise and cytokines with particular focus on muscle-derived IL-6. Exerc Immunol Rev 7:18–31PubMedGoogle Scholar
  78. 78.
    Thune I, Furberg AS (2001) Physical activity and cancer risk: dose-response and cancer, all sites and site-specific. Med Sci Sports Exerc 33:S530–S550PubMedCrossRefGoogle Scholar
  79. 79.
    Lynch BM (2010) Sedentary behavior and cancer: a systematic review of the literature and proposed biological mechanisms. Cancer Epidemiol Biomarkers Prev 19:2691–2709PubMedCrossRefGoogle Scholar
  80. 80.
    Dunstan DW, Salmon J, Owen N, Armstrong T, Zimmet PZ, Welborn TA et al (2005) Associations of TV viewing and physical activity with the metabolic syndrome in Australian adults. Diabetologia 48:2254–2261PubMedCrossRefGoogle Scholar
  81. 81.
    Dunstan DW, Barr ELM, Healy GN, Salmon J, Shaw JE, Balkau B et al (2010) Television viewing time and mortality. The Australian diabetes, obesity and lifestyle study (AusDiab). Circulation 121:384–391PubMedCrossRefGoogle Scholar
  82. 82.
    Owen N, Bauman A, Brown W (2009) Too much sitting: a novel and important predictor of chronic disease risk. Br J Sports Med 43:81–83PubMedCrossRefGoogle Scholar
  83. 83.
    Ballard-Barbash R, Hunsberger S, Alciati MH, Blair SN, Goodwin PJ, McTiernan A et al (2009) Physical activity, weight control, and breast cancer risk and survival: clinical trial rationale and design considerations. J Natl Cancer Inst 101:630–643PubMedCrossRefGoogle Scholar
  84. 84.
    Courneya KS, Booth CM, Gill S, O’Brien P, Vardy J, Friedenreich C et al (2008) The colon health and life-long exercise change (CHALLENGE) trial (CO.21). Curr Oncol 15:8–16CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Brooke M. Winzer
    • 1
    • 4
  • David C. Whiteman
    • 2
  • Marina M. Reeves
    • 3
  • Jennifer D. Paratz
    • 1
  1. 1.School of Medicine, Burns, Trauma & Critical Care Research CentreThe University of QueenslandBrisbaneAustralia
  2. 2.Centre for Cancer ControlQueensland Institute of Medical ResearchBrisbaneAustralia
  3. 3.School of Population Health, Cancer Prevention Research CentreThe University of QueenslandBrisbaneAustralia
  4. 4.Level 7, Block 6, Royal Brisbane & Women’s HospitalHerstonAustralia

Personalised recommendations