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Energy Balance and Cancer Survival

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  1. Energy Balance and Cancer Survival Michelle D. Holmes, MD, DrPH November 11, 2005

  2. Cancer Survivorship • 62% 5 year survival over all adult cancers • 8.9 million US cancer survivors • 22% breast cancer (2 million) • 19% prostate cancer (1.7 million) • 11% colorectal cancer (1 million) Aziz; J Nutr 2002; 132: 3494S

  3. Topics • Energy balance (obesity, weight gain, activity) • Breast Cancer • Colon Cancer • Dietary fat and breast cancer

  4. Breast Cancer

  5. Energy BalanceObesity

  6. Energy BalanceObesity 1985 vs. 1987

  7. Energy BalanceObesity 1985 vs. 1989

  8. Energy BalanceObesity 1985 vs. 1991

  9. Energy BalanceObesity 1985 vs. 1993

  10. Energy BalanceObesity 1985 vs. 1995

  11. Energy BalanceObesity 1985 vs. 1997

  12. Energy BalanceObesity 1985 vs. 1999

  13. Energy BalanceObesity 1985 vs. 2001

  14. Energy BalanceObesity 1985 vs. 2003

  15. Obesity  Decreased Survival

  16. Energy BalanceWeight Gain

  17. Chemotherapy  Weight Gain Goodwin PJ, J Clin Oncol 1999; 17:120

  18. Weight Gain →↓Survival Relative risk of breast cancer death by category of weight change among 5,204 women with breast cancer from the NHS Kroenke CH, J Clin Onc 2005;23: 1370

  19. Exercise

  20. Exercise and Breast Cancer Survivors • Improves body esteem and mood • Enhances quality of life • Can it improve survival? • Might prevent weight gain with chemotherapy • Might lower hormone levels known to stimulate cancer growth

  21. Metabolic Equivalent Conversions

  22. NHS Study Participants • Invasive breast cancer 1984-2002 • Stages I, II, III • Activity assessment ≥ 2 years after diagnosis

  23. Physical activity after diagnosis • This is what a woman with breast cancer can change Avoided women with occult metastatic disease • Likely to affect activity levels

  24. Multivariate RR of Death, and Breast Cancer Death, by Physical Activity Holmes MD, JAMA 2005;293:2479

  25. Multivariate RR of Death from Breast Cancer, by Physical Activity,Stratified by ER/PR status P for interaction = 0.08

  26. Mortality curves by exercise level

  27. Mechanisms for Energy Balance Affecting Breast Cancer Survival • Sex steroid hormones

  28. Mean Serum Hormones x BMI in 503 Women with Breast Cancer McTiernan A, JCO 2003; 21:1961

  29. RTC • 173 overweight postmenopausal women • Moderate exercise 5 days/week x 12 months • Controls=stretching • Exercisers vs. Controls Irwin ML, JAMA 2003;289:323

  30. Estradiol (pg/mL) levels McTiernan A, CEBP 2004;13:1099

  31. Colon Cancer

  32. Energy Balance (Obesity) • Cohort study 3759 men & women • Stage II, III colon cancer • INT-0089 trial • 4 treatment aims • No survival difference by treatment • f/u = 9.4 years • Categorized by BMI (kg/m2) at time of Rx • Meyerhardt, Cancer 2003

  33. Energy Balance (Obesity) Adjusted HR (85% CI) By BMI

  34. Mechanisms for Energy Balance Affecting Colon cancer survival • Insulin/C-peptide/IGFs • Leptin/Adiponectin/Inflammatory markers

  35.  Energy intake,  Physical activity,  High Glycemic diet  Competent beta-cell secretion  C-peptide Hyperinsulinemia (Fasting or Post-Prandial)  Pituitary GH secretion  IGF-I response to GH Obesity  Insulin resistance  IGFBP-1  Bioactive IGF-I Direct effect? Cell survival and proliferation

  36. RR Colon Cancer (NHS) High insulin production Low insulin production Years Since Diagnosis of Diabetes Hu et al., JNCI 1999

  37. C-peptide Levels & Colorectal Cancer Risk in Men (PHS) Ptrend <0.05 RR ref Plasma C-peptide Ma, et al. J Natl Cancer Inst 2004

  38. Biological Function of White Adipose Tissue appetite and energy balance (leptin) immunity haemostasis insulin sensitivity (adiponectin) lipid metabolism Angiogenesis (VEGF) blood pressure inflammation & acute-phase response (IL-6, CRP, TNF-) (Trayhurn and Wood et al. 2004)

  39. Leptin, BMI and Risk of Colorectal Cancer (Sweden) OR OR Ptrend=0.02 Ptrend=0.08 ref ref Leptin BMI Stattin et al. Oncology Reports, 2003

  40. Dietary Fat and Breast Cancer Survival

  41. Cohort studies of fat intake and breast cancer survival, by timing of dietary assessment(Author & year, N, Hazard Ratio)

  42. WINSRTC of low fat diet 2437 women with postmenopausal breast cancer 975 women Low fat diet (33.3 g/day) 1462 women Standard diet (51.3 g/day) 5 yrs

  43. WINSlow fat diet vs. control

  44. WINS Trial • Pilot studies showed • Good adherence to diet • Average weight decrease 2 kg • Average estradiol decrease 20%

  45. Conclusions • Adjuvant treatments for breast & colon cancer lowers disease mortality 25-40% • Weight maintenance after breast cancer may lower disease mortality ∼ 40% • Moderate exercise after breast & colon cancer may lower disease mortality ∼ 40-50%

  46. Conclusions • Advising weight maintenance and exercise after breast & colon cancer may help our patients as much as standard treatments. • Important in our sedentary & obesigenic environment.