Energy Balance and Cancer Survival

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Energy Balance and Cancer Survival

• Michelle D. Holmes, MD, DrPH
• November 11, 2005

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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
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Topics

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

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Breast Cancer
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Energy BalanceObesity
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Energy BalanceObesity 1985 vs. 1987
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Energy BalanceObesity 1985 vs. 1989
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Energy BalanceObesity 1985 vs. 1991
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Energy BalanceObesity 1985 vs. 1993
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Energy BalanceObesity 1985 vs. 1995
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Energy BalanceObesity 1985 vs. 1997
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Energy BalanceObesity 1985 vs. 1999
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Energy BalanceObesity 1985 vs. 2001
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Energy BalanceObesity 1985 vs. 2003
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Obesity ? Decreased Survival
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Energy BalanceWeight Gain
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Chemotherapy ? Weight Gain
Goodwin PJ, J Clin Oncol 1999 17120
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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 200523 1370
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Exercise
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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

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Metabolic Equivalent Conversions
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NHS Study Participants

• Invasive breast cancer 1984-2002
• Stages I, II, III
• Activity assessment 2 years after diagnosis

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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

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Multivariate RR of Death, and Breast Cancer
Death, by Physical Activity
Holmes MD, JAMA 20052932479
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Multivariate RR of Death from Breast Cancer, by
Physical Activity,Stratified by ER/PR status
P for interaction 0.08
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Mortality curves by exercise level
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Mechanisms for Energy Balance Affecting Breast
Cancer Survival

• Sex steroid hormones

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Mean Serum Hormones x BMI in 503 Women with
Breast Cancer
McTiernan A, JCO 2003 211961
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RTC

• 173 overweight postmenopausal women
• Moderate exercise 5 days/week x 12 months
• Controlsstretching
• Exercisers vs. Controls

Irwin ML, JAMA 2003289323
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Estradiol (pg/mL) levels
McTiernan A, CEBP 2004131099
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Colon Cancer
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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

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Energy Balance (Obesity)
Adjusted HR (85 CI) By BMI
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Mechanisms for Energy Balance Affecting Colon
cancer survival

• Insulin/C-peptide/IGFs
• Leptin/Adiponectin/Inflammatory markers

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? 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
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RR Colon Cancer (NHS)
High insulin production
Low insulin production
Years Since Diagnosis of Diabetes
Hu et al., JNCI 1999
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C-peptide Levels Colorectal Cancer Risk in Men
(PHS)
Ptrend RR
ref
Plasma C-peptide
Ma, et al. J Natl Cancer Inst 2004
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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)
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Leptin, BMI and Risk of Colorectal Cancer
(Sweden)
OR
OR
Ptrend0.02
Ptrend0.08
ref
ref
Leptin
BMI
Stattin et al. Oncology Reports, 2003
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Dietary Fat and Breast Cancer Survival
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Cohort studies of fat intake and breast cancer
survival, by timing of dietary assessment(Author
year, N, Hazard Ratio)
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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
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WINSlow fat diet vs. control
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WINS Trial

• Pilot studies showed
• Good adherence to diet
• Average weight decrease 2 kg
• Average estradiol decrease 20

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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

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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.