Cancer and Exercise

1. Cancer and Exercise B. Elizabeth Delasobera, MD Sports Medicine Fellow

2. Outline • The mechanism for how exercise can prevent cancer • The evidence for exercise and increased cancer survival • The exercise prescription for cancer patients and survivors

3. Cancer Review • Excessive, uncontrolled cellular proliferation with potential for metastasis • Symptoms can be local or systemic • Variety of treatments • Surgery, Radiation, Chemotherapy, Immunotherapy • Designed to attempt remission or cure, or for disease control or symptom relief

4. Mechanism for Cancer Reduction with Exercise • Physical activity lowers levels of biologically available sex hormones • Decreased lifetime exposure to endogenous sex hormones -> decreased risk of hormone-related cancers • Breast, endometrial, ovaries, prostate, testes

5. Mechanism for Cancer Reduction with Exercise • Exercise decreases endogenous insulin production • Higher levels of circulating insulin linked with several cancers • Exercise associated with decreased levels of IGF • High levels of IGF-1 a/w several cancers (colon, prostate, breast, lung)

6. Mechanism for Cancer Reduction with Exercise • Adiposity and Cancer Risk • Increased fat associated with increased risk of cancers of colon, kidney, esophagus, endometrium, thyroid, post-menopausal breast • Physical activity decreases colon transit time • Decreases colonic exposure to carcinogens in stool • Level of physical activity inversely related to levels of C-reative protein • NSAID use in physically active • NSAID use appears to decrease colon cancer risk

8. The Evidence:Exercise and Cancer Risk • Breast Cancer • Invasive Breast Cancer risk decreased by 15%-50% among physically active women • Women < 40yo exercising 4 hrs/week or more during reproductive years had 50% risk reduction • Postmenopausal women with higher rates of recreational activity have lower incidence of breast cancer • Confirmed in over 30 studies in multiple demographic and population groups • Studies focused solely on in situ Breast Cancer have shown similar reductions in risk • Estrogren receptor negative cancer seem to be most reduced with exercise Bernstein L, AACR Education Book 2008:225-231 (2008)

9. The Evidence:Exercise and Cancer Risk • Breast Cancer • Greatest reduction is risk found with exercise during reproductive years, strenuous activity, at least 5 hours per week • Estrogen receptor-negative Breast Cancer responds better to exercise than receptor-positive cancer • Meta-analysis revealed a dose-response relationship of 6% decrease in relative risk for each additional hour of physical activity per week Monninkhof EM, et al. Epidemiol 2007;18:137–57. Bernstein L, AACR Education Book 2008:225-231 (2008)

10. The Evidence: Exercise and Cancer Survival • Breast Cancer Survival Meta-Analysis • 24% - 67% reduction in total deaths and 50% reduction in breast cancer recurrence in women who are physically active • Best effect in women who underwent equivalent of brisk walking 3h per week • Effect observed in pre and post-menopausal, overweight and normal weight women, and those with stage I-III disease

11. The Evidence:Exercise and Cancer Risk • Colon Cancer • 43 out of 51 studies demonstrated decreased risk of colon cancer in the most physically active participants • Risk reduction averaged 40%-50%, up to 70% • Consistent risk reduction despite differing study designs and populations and types of exercise • Greater effect in men vs. women • Hormone supplementation in postmenopausal women also has protective effect • Unclear exercise effect on rectal cancer Bernstein L, AACR Education Book 2008:225-231 (2008) Friedenreich CM, et al. J Nutr 132:3456-3464, 2002.

12. The Evidence: Exercise and Cancer Survival • Colon cancer survival • 3h per week of moderate physical activity after colon cancer diagnosis: • 39%-59% decreased risk of colon cancer death • 50%-63% decreased risk of total death • Effect essentially unchanged across age, sex, BMI, disease stage, age at diagnosis • Meyerhardt JA, et al. J Clin Oncol 2006;24:3535–41

13. The Evidence:Exercise and Cancer Prevention • Prostate Cancer • Less consistent data, risk reduction averaged 10% - 30% • Poor understanding of natural history of Prostate Cancer • Exercise can also reduce risk of BPH • Exercise lowers severity of disease and fatalities from prostate cancer • Likely that very high level of exertion early in life needed to influence implicated hormones Bernstein L, AACR Education Book 2008:225-231 (2008) Friedenreich CM, et al. J Nutr 132:3456-3464, 2002.

14. The Evidence:Exercise and Cancer Prevention • Endometrial Cancer • Strong association with Breast Cancer • Fewer/lower quality studies • Majority still show decreased risk of endometrial cancer with increased physical activity • Risk Reduction varied: 0 – 90%, average 30% - 40% • Majority of studies show dose response effect Bernstein L, AACR Education Book 2008:225-231 (2008) Friedenreich CM, et al. J Nutr 132:3456-3464, 2002.

15. The Evidence:Exercise and Cancer Prevention • Lung Cancer • Physical activity probably decreases risk of lung cancer, but effect not well-established • Meta-analysis shows 13% risk reduction with moderate recreational physical activity and 30% decreased risk with strenuous activity • Studies may not reflect differences in smoking habits Tardon A, et al. Cancer Causes Control 2005;16:389–97.

16. The Evidence:Exercise and Cancer Prevention • Limited and/or insufficient evidence: • Ovarian Cancer • Testicular Cancer • Renal Cell Cancer • Pancreatic Cancer • Thyroid Cancer • Melanoma

17. Survivors and Obesity • Improvements in treatment means more survivors • 11 million cancer survivors in US alone • Obesity and a sedentary lifestyle prevalent among cancer survivors (Irwin ML, BJSM 2009;43:32-38) • Higher than general population • Increases risk of cancer recurrence and death • In breast cancer survivors, obesity assoc w/ 50% increase in cancer recurrence and death (Kroenke CH, et al. J Clin Oncol 2005;23:1370–8) • Cancer survivors die from non-cancer related CVD and DM2 at a higher rate than the general population

18. So Are Cancer Pts Exercising? • Despite these well documented dramatic effects, the great majority of cancer survivors do not participate in regular physical activity • Many cancer survivors decrease their physical activity after diagnosis • Women with breast cancer exercise, on average, 2 hours less per week 1 year after diagnosis than pre-diagnosis.

20. Recs for Exercising with Cancer • Goal is to preserve and possibly improve function • Must be individualized • Tailor to level of function • Accommodate for periods of increased fatigue and cycles of treatment • Make exercise an integral part of everyday life

21. Recs for Exercising with Cancer • 30-50% of breast cancer deaths among post-menopausal women can be attributed to being overweight • Cancer survivors die of non-cancer causes at a higher rate than persons in the general population (CV dz, DM, etc)

22. Recs for Exercising with Cancer • Special Considerations for Cancer and Exercise: • Cancer treatment can cause osteoporosis; bony metastases may weaken bone = higher risk of pathologic fracture • Be aware of Hickman cathethers, Port-a-caths, other access lines • If platlet count is below 50k, consider risk of bleeding • Consider concomitant effects of CVD and anemia

23. Recs for Exercising with Cancer • Medications That Can Effect Exercise Tolerance: • Glucocorticoids: may cause muscle weakness and wasting • Growth factors: may cause bone pain • Chemotherapy: may cause anemia, fatigue, and nausea; possibly myopathies and neuropathies • Anthracyclines can cause cardiomyopathy, heart failure and coronary vasospasm • Radiation: may cause skin breakdown, muscle and joint constriction, and cardiopulmonary fibrosis

24. Recs for Exercising with Cancer

25. Recs for Exercising with Cancer • American Cancer Society Recs: • While getting adjuvant treatment recs 3-5 days/week for 20-30 mins tailored to fitness level and tx side effects (ex, walking, resistance training, yoga) • Survivors use ACSM sports prescription guidelines (keep in mind any limitations based on prior slides)

26. Recs for Exercising with Cancer • Things to Keep in Mind with Return to Sport: • Immunocompromised? (neutropenia, on chemo, etc) • At risk of bleeding? (platlet count, coags, meds) • At risk of CV issues? (meds) • “Neck check”

28. Summary • Multiple biologic explanations for benefits of exercise with respect to cancer risk reduction and survival • Exercise and Cancer Prevention • Convincing evidence for increased activity and prevention of colon, breast, and prostate cancer • Probable evidence for endometrial and lung cancer • Insufficient evidence for all others

29. Summary • Exercise and Cancer Survival • Increasing numbers of survivors in population • Decreasing physical activity among survivors • Increased physical activity significantly lowers cancer recurrence and total death in survivors • Exercise Prescription • Must be individualized • Many confounding factors (be aware of meds and side effects) • Keep it simple, make it regular, progress gradually