Actividad Física y Cáncer

Actividad Física y Cáncer
Mauricio Serrato Roa Medicina del Deporte Facultad de Medicina Profesor Asociado U. Nacional

such as diabetes, hypertension
What if there was one prescription that could prevent and treat dozens of diseases, such as diabetes, hypertension and obesity? -Robert E. Sallis, M.D., M.P.H., FACSM, Exercise is Medicine™ Task Force Chairman

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Índice Asociación entre Cáncer y Actividad Física
Mecanismos de acción del la Actividad Física Ejercicio en paciente con cáncer Conclusiones

Asociación entre cáncer y AF
En 1922 dos estudios encontraron la asociación entre el Cáncer y el trabajo físico muscular. CHERRY, T. A theory of cancer. Med. J. Aust. 1:425–438, 1922. SIVERTSEN, I., and A. W. DAHLSTROM. The relation of muscular activity to carcinoma: a preliminary report. J. Cancer Res. 6:365– 378, 1922. Ilkka M. Vuori, MD, PhD; Carl J. Lavie, MD; and Steven N. Blair, PED. Physical Activity Promotion in the Health Care System. Mayo Clin Proc. December 2013;88(12):

Cáncer y Ejercicio La agencia internacional para la investigación en cáncer, estima que ⅓ de los canceres de colon, seno, endometrio, esófago (adenocarcinoma) y riñón (células renales) pueden ser atribuidos a obesidad y sedentarismo

Evidencia Epidemiológica
El riesgo de cancer de colon varía inversamente con el nivel de AF Harvard Alumni study 30 min de actividad física moderada 5X/sem tuvo una reducción de 50% Nurses’ Health Study 5 hr /sem de actividad moderada a intense tuvieron una reducción del riesgo de un 45% Lee, I-min. et al. Physical Activity and Cancer Prevention. Data From Epidemiologic Studies. Medicine and Science in Sports and Exercise (11)

La Evidencia, Cancer de Colon
Reducción del riesgo en promedio 40%-50%, hasta 70% Efecto consistente entre estudios de diferente diseño y población Mayor efecto en hombres Bernstein L, AACR Education Book 2008: (2008) Friedenreich CM, et al. J Nutr 132: , 2002.

Cáncer de Colon RR de 0.7 para hombres RR de 0.6 para mujeres
30-40% reducción del riesgo. Gasto mínimo >1000 kcal/sem Actividad moderada a vigorosa Harriss DJ. Lifestyle factors and colorectal cancer risk (2): a systematic review and meta-analysis of associations with leisure-time physical activity. COLORECTAL DISEASE 2009a; 11: LEE, I.-M., R. S. PAFFENBARGER, Jr., and C. HSIEH. Physical activity and risk of developing colorectal cancer among college alumni. J. Natl. Cancer Inst. 83:1324–1329, 1991

Riesgo relativo de Cáncer de colon por AF en tiempo libre
P trend = 0.03 Reducción en 50% del riesgo de desarrollar cáncer de colon US Nurses Health Study – followed 67,802 women for 6 years Nurses reported average time per wk in specified activities, used to estimate total ‘volume’ in MET x h per wk Adjusted for age, cigarette smoking, family history of disease, BMI, postmenopausal hormone use, aspirin use, intake of red meat and alcohol consumption Walking was the most common leisure activity, reported by 70% of respondents >21 MET x h per week vs <2 MET x h per week (Low end of range, relative to upper end of range, 50% reduction in colon cancer risk). 21 MET x h equivalent to about 5 h of moderate activity, e.g. brisk walking. Mid point of this category, 16 MET-h per week equivalent to 4 h per week of moderate intensity activity OR around 5 h of moderate or 3.5 h of high intensity activity per week. High BMI is a risk factor (BMI > 29 vs. < 21 conferred 45% higher risk). Effect of activity independent of BMI, I.e. activity effect is not only to help avoid overweight. effect for distal colon cancer, not proximal Martínez et al J Natl Cancer Inst 1997;89:948

Actividad Física-Fitness y Cáncer Colon
Lee I. et al. Physical activity and risk of developing colorectal cáncer among college alumni. Journal of the national cáncer Institute. 83;

AF y riesgo de Cáncer de Seno
RR de 0.8 para mujeres RR 0.7 en posmenopáusicas 30-60 min diarios de actividad moderada a vigorosa 4hr semana redujeron 37% el riesgo THUNE, I., T. BRENN, E. LUND, and M. GAARD. Physical activity and the risk of breast cancer. N Engl. J. Med. 336:1269–1275, 1997.

Actividad Física – Fitness y Ca de seno
Selected because >25 thousand women AND because the study was based on a 10% random sample of women in 3 counties in Norway. 2 assessments of activity at an interval of 3-5 y, results combined. Median follow-up 14 y. Leisure time: Grade 1 – reading, TV etc Grade 2 - > 4h per week walking, bicycling etc. Grade 3 – regular, vigorous training or competitive sports at least 3 times per week. Occupational: Grade 2 – a lot of walking; Grade 3 – lot of lifting and walking; Grade 4 – heavy manual labour. Results, based on adjustments for age, BMI, county of residence, number of children and height; Recreational Grade 3 - RR Occupational – p for trend = % lower risk in women engaged in heavy manual labour. In this study, more pronounced effect in premenopausal than in postmenopausal women. Stronger effects in women consistently active over the two observations. despite size of cohort, only 351 cases identified. Underlines the valuable, complementary evidence from case control studies Thune, I. et al. Physical activity and the risk of breast cáncer. N eng J Med, 336:

US Women’s Health Initiative Cohort Study
US Women’s Health Initiative Observational Study – multi-ethnic. Cohort of > 74,000 women aged at recruitment. Mean follow-up of 4.7 y at 40 clinical centres, during which time 1780 new cases of cancer were diagnosed. Data on frequency of participation in low-intensity, moderate-intensity and strenuous exercise. Not only current but also, by recall, at ages18, 35 and 50 average of 5.1 – 10 METs (1.25 – 2.5 h/wk of brisk walking) had significant 18% lower risk, compared with sedentary women. Again – appears to be total activity that has most important effect. Findings not dissimilar to those of large Nurses Health Study (Rockhill 1999) – 4-7 h/wk mod or vig.. 15% lower risk, cf <1 h/wk. > 7 h slightly larger reduction, I.e. 18% McTiernan A et al. Recreational physical activity and the risk of breast cancer in postmenopausal women: the Women's Health Initiative Cohort Study. JAMA 2003:290:1331-6

Interacción entre la AF y el BMI
Possible interaction with BMI Effect of exercise strongest in the lowest tertile of BMI (<24.1) but was also observed for women in the middle tertile (24.1 – 28.4). McTiernan A et al JAMA 2003;290:1331-6

Evidencia Riesgo Cancer Seno
Reduce el riesgo de cancer invasivo entre 15-50% Mujeres < 40 años, 4 hr/semana durante edad reproductiva redujeron 50% riesgo Mujeres posmenopáusicas con mas AF tienen menor incidencia Efecto similar en los tumores in situ Los tumores con receptores de estrógeno negativos se benefician mas del ejercicio. Bernstein L, AACR Education Book 2008: (2008)

Evidencia – Dosis Respuesta
Meta-analysis reveló la relación dosis respuesta de una disminución en 6% en el RR por cada hora adicional de ejercicio a la semana Monninkhof EM. Et al. Physical activity and breast cancer: a systematic review. Epidemiology Jan;18(1):137-57

Cáncer de Pulmón RR de 0.8 – reducción promedio de 20%
Caminaron o montaron cicla por al menos 4hr/sem tuvieron 25% menos riesgo de adenocarcinoma no para escamocelular. THUNE, I., and E. LUND. The influence of physical activity on lung-cancer risk: a prospective study of 81,516 men and women. Int. J. Cancer 70:57–62, 1997.

Actividad Física – Fitness y Cáncer pulmonar
↓39% Lee I. et al. Physical activity and risk of lung cáncer. Int J Epidemiol. 28:

Cáncer de Endometrio Actividad en la vida diaria y riesgo de cáncer de endometrio Estudio de casos y controles de 472 mujeres comparadas con controles Las mujeres mas activas tuvieron 56% menos probabilidad de desarrollar cáncer de endometrio Cancer Epidemiology Biomarkers and Prevention. 2010:19(5);

Mecanismos asociados con la etiología y actividad física
La AF al afectar la obesidad resulta en cambios en adipokinas circulantes y citokinas, resistencia a la insulina, niveles de insulina y producción de hormonas esteroideas. Nature Reviews Cancer. Vol 8. March 2008

Mecanismos Asociados Hypothesized mechanisms linking physical activity to cancer risk or prognosis. Physical activity might work through reducing the amount of adipose tissue, which lowers production of sex hormones, insulin, leptin and inflammatory markers, thereby decreasing the exposure to these potentially carcinogenic hormones and peptides and reducing cancer risk. Anne McTiernan. Mechanisms linking physical activity with cáncer. Nature Reviews Cancer. Vol 8. March 2008

Otros Mecanismos Actividad Física ↑Motilidad Intestinal
↓ Tiempo transito y exposición a carcinógenos Actividad Física ↓PG E2 carcinogénica ↓ daño oxidativo DNA y reparación McTiernan, A., Ulrich, C., Slate, S. & Potter, J. Physical activity and cancer etiology: associations and mechanisms. Cancer Causes Control 9, 487–509 (1998). Martinez, M. E. et al. Physical activity, body mass index, and prostaglandin E2 levels in rectal mucose. J. Natl Cancer Inst. 91, 950–951 (1999). Meijer, E. P., Goris, A. H., van Dongen, J. L., Bast, A. & Westerterp, K. R. Exercise-induced oxidative stress in older adults as a function of habitual activity level. J. Am. Geriatr. Soc. 50, 349–353 (2002).

Efecto de la AF y % graso en Hormonas
We conducted a physical activity trial in 173 overweight, sedentary postmenopausal women (BMI ≥ 24 kg/m2 and percentage body fat > 33%), in which women were randomized to a moderate-intensity aerobic exercise, 45 min/day, 5 days/week for 12 months or to a control group. A significant decrease in oestradiol, oestrone and free oestradiol was seen from baseline to 3 months, with an attenuation of the effect at 12 months31. However, in those women who lost body fat, the exercise intervention resulted in a statistically significant reduction in these oestrogens at both 3 and 12 months (FIG. 3a). Similarly, in women who lost body fat, there was a statistically significant decrease in testosterone and free testosterone in exercisers compared with controls32 (FIG. 3b). These results suggest that both increased physical activity and reduced body fat will produce the greatest protection against breast cancer by producing the greatest decrease in serum sex hormones. Hormone changes by change in body fat with physical activity in sedentary or overweight postmenopausal women (aged 50–75 years). a | Percent change in oestradiol by percent change in body fat as measured by dual-energy X-ray absorptiometry (DEXA) scan. A statistically significant difference in oestradiol level was observed in exercisers who lost 0.5–2% body fat (P = 0.02) and for those who lost > 2% body fat (P = 0.008) compared with controls at 12 months31. b | Percent change in testosterone by percent change in body fat as measured by DEXA scan. A statistically significant difference in testosterone level was observed in exercisers who lost 0.5–2% body fat (P < 0.05) and for those who lost >2% body fat (P<0.05) compared with controls at 12 months32. c | Percent change in insulin by percent change in body fat as measured by DEXA scan. A statistically significant difference in insulin level was observed in exercisers who lost 0.5–2% body fat and for those who lost > 2% body fat compared with controls at 12 months (P = 0.03)12. McTiernan, A. et al. Relation of BMI and physical activity to sex hormones in postmenopausal women. Obesity (Silver Spring) 14, 1662–1677 (2006). Frank, L. L. et al. Effects of exercise on metabolic risk variables in overweight postmenopausal women: a randomized clinical trial. Obes. Res. 13, 615–625 (2005).

Hormonas Metabólicas Asociación entre resistencia a IN y cáncer de seno, colon, páncreas y endometrial IN aumenta crecimiento tumoral e inhibe apoptosis Regula la síntesis de hormonas esteroideas e inhibe las globulinas ligadoras El ejercicio resulta en mejoría crónica en la Resistencia a Insulina Kaaks, R. & Lukanova, A. Energy balance and cancer: the role of insulin and insulin-like growth factor-I. Proc. Nutr. Soc. 60, 91–106 (2001).

Inflamación Actividad Física MAC ↓ Riesgo Cáncer ↓ % graso Adipocito
↓IGF1 ↓CRP Actividad Física MAC ↓SAA ↓ Riesgo Cáncer ↓ IL-6 ↓ % graso Adipocito ↓ TNFα serum amyloid A ↑Adiponectin Anne McTiernan. Mechanisms linking physical activity with cáncer. Nature Reviews Cancer. Vol 8. March 2008

Sistema Inmune Las células anormales son eliminadas por componentes del sistema inmune innatos y adquiridos La AF pude mejorar el numero y función de las células NK, las cuales juegan un papel en la supresión de tumores. Wetmore, C. M. & Ulrich, C. M. in Cancer Prevention and Management through Exercise and Weight Control (ed. McTiernan, A.) 157–175 (CRC Taylor Francis, Boca Raton, 2006).

Vigilancia Inmunológica
+ Physical Activity

Goh J et al. Exerc Immunol Rev. 2012;18:158-76

Prevención Secundaria
“In other words, exercise may be a critical strategy to modulate the host–tumor interaction” (Goodwin, 2008). Goodwin PJ. Host-related factors in breast cancer: an underappreciated piece of the puzzle? J Clin Oncol. 2008; 26:3299–3300.

Evidencia – Sobrevida del Cancer
24% - 67% reducción en muertes totals y 50% en recurrencia en mujeres activas Mejor efecto en quienes hacian caminata rápida 3 h semana Efecto observado en pre y posmenopáusicas, sobrepeso y normales, y con estadios I-III Monninkhof EM. Et al. Physical activity and breast cancer: a systematic review. Epidemiology Jan;18(1):137-57

Evidencia - Sobrevida 3 hr/sem de AF moderada
39%-59% reduce riesgo de 50%-63% Efecto sostenido a lo largo de la edad, sexo, IMC, estadio, edad y diagnóstico Meyerhardt JA, et al. Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB J Clin Oncol 2006;24:3535–41

Cáncer de Seno y Actividad Física sobrevida
Mujeres en estadio III, que realizaron ≥9 MET·h/week de AF El RR fué (95% CI 0.19–0.71). Holmes, M. D., Chen, W. Y., Feskanich, D., Kroenke, C. H. & Colditz, G. A. Physical activity and survival after breast cancer diagnosis. JAMA 293, 2479–2486 (2005).

Prevención Secundaria - Mecanismos
Evidence-based representation of the known effects and mechanisms of exercise on tumor progression adopting a bi-directional translational research or scientific discovery (T0) paradigm. Exercise/fitness and prognosis, evidence supporting association between self-reported exercise behavior, objective measures of exercise capacity or functional capacity, and cancer prognosis; Host-Related Factors, postulated systemic (host-related) pathways mediating the association between exercise behavior and exercise/functional capacity and cancer prognosis; Tumor-Related Factors, intratumoral factors shown to mediate the association between exercise and prognosis or factors shown to be modulated in response to exercise. +++, strong evidence; ++, moderate evidence; +, weak evidence; —, null; ?, unknown at present. Allison S. Betof, Mark W. Dewhirst, and Lee W. Jones*. Effects and potential mechanisms of exercise training on cancer progression: A translational perspective Brain Behav Immun. Mar 2013; 30(0): S75–S87.

Conclusión Prevención Primaria
Existe evidencia epidemiológica (>100 estudios) LA AF rutinaria parte del trabajo o tiempo libre reduce la incidencia Particularmente en Cáncer de Colon (30-40%)y Seno (20-30%) AF moderada 4.5 METs Lee IM. Physical activity and cancer prevention--data from epidemiologic studies.Med Sci Sports Exerc Nov; 35(11): Thune I, Furberg AS. Physical activity and cancer risk: dose-response and cancer, all sites and site-specific. [discussion S609-10]. Med Sci Sports Exerc2001; 33: S530-50

Conclusión Prevención Secundaria
Aumento de la AF disminuye la recurrencia del cáncer y riesgo de muerte (1) Valores de 26 a 40% de reducción en el RR. Efecto de la AF en la quimioterapia (2) La AF regular se asocia con mejora en la calidad de vida y estado de salud (3) 1- Physical activity and survival after breast cancer diagnosis.Holmes MD, Chen WY, Feskanich D, Kroenke CH, Colditz GA JAMA May 25; 293(20): 2- Haydon AM, Macinnis R, English D, et al The effect of physical activity and body size on survival after diagnosis with colorectal cancer. Gut 2005;1:62-7. 3- Galvao DA, Newton RU. Review of exercise intervention studies in cancer patients.Galvão DA, Newton RU J Clin Oncol Feb 1; 23(4):

Gracias mserrator@unal.edu.co Facultad de Medicina
Departamento de Medicina Interna

Recs de Ejercicio para Pacientes con Cancer
American Cancer Society: 3-5 days/week for mins de acuerdo con el nivel de fitness y efectos secundarios del tratamiento. (ej, caminar, pesas, yoga) Usar las guias de prescripción del ACSM

Tener en mente para retornar a su deporte: Esta Inmunocomprometido? (neutropenia, en quimio, etc) Riesgo de sangrado? (plaquetas, coagulación, meds) Riesgo cardiovascular por meds

Se ejercitan los pacientes con cáncer?
A pesar de los efectos documentados tan dramáticos, la mayoria de los pacientes no participant en AF regular Mucos pacientes disminuyen su nivel de AF despues del Dx Las mujeres con Cancer d eSeno, en promedia 2 hr menos por semana

La meta es preservar y posiblemente mejorar la función Debe ser individualizado Nivel de funcionalidad Acomodar por periodos de fatiga y ciclos de tratamiento Hacer del ejercicio parte integral de la vida diaria

30-50% de los pacientes con cancer entre las posmenopáusicas pueden atribuirse al sobrepeso Los sobrevivientes de cancer mueren por causas no cancerigenas en una mayor taza que la población general. (CV, diabetes, etc)

Consideraciones especiales por cancer y ejercicio: EL tratamiento de cancer puede causar osteoporosis, las metastasis pueden debilitar el huesto y llevar a riesgo de fractura patológica. Cuidado con los catetees y otras líneas de acceso Si la cuenta de plaquetas es menor a 50k, considere el riesgo de sangrado Considere los efectos concomitantes de la enfermedad cardiovascular y anemia.

Los medicamentos pueden tener efecto en la tolerancia al ejercicio: Glucocorticoides: debilidad muscular Factores de crecimiento: dolor óseo Quimioterapia: anemia, fatiga, nausea, miopatias y neuropatias Antraciclinas pueden causar cardiomiopatia, falla cardiaca y vasoespasmo coronario Radioterpia: púede causar ruptura de la piel, restricción en la articulación y fibrosis cardiopulmonar

Physical activity and breast cancer: case-control study
Population-based case-control study, women aged up to 84 in Canada.Total of 1233 cases, 1237 controls, examined according to menopausal status. (12 x number cases in Thune just referred to) Strength - Interview administered questionnaire on pa over lifetime, including occupational, household, recreational data corrected for: age,menstrual history, use of contraceptive pill, parity, breast feeding, WH ratio, educational level, ever used HRT, ever diagnosed with benign breast disease, family history, smoking, alcohol use 30% decreased risk for high total lifetime activity (OR 0.6, CI ) after menopause. (This comparison for lowest quartile vs highest quartile.) Overall evidence on menopausal status, based on 40 studies (Friedenreich 2004). Stronger and more consistent effect is observed for postmenopausal women. Friedenreich et al Am J Epidemiol 2001;154:336-47

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