Lifestyle Factors and Cancer Survivorship: Observational Findings of Weight, Physical Activity, and Diet on Survival Melinda L. Irwin, PhD, MPH Associate Professor of Epidemiology Yale School of Medicine Yale School of Public Health
AICR s 2009 Annual Research Conference on Food, Nutrition, Physical Activity and Cancer November 5-6, 2009 Capital Hilton, Washington, DC No Relevant Financial Relationships No Conflict of Interest
Lifestyle Habits and Breast Cancer Survival Despite advances in adjuvant treatment, over 40,000 women still die of breast cancer each year. Current breast cancer therapies do not address the association of obesity and sedentary lifestyle effects on prognosis. Obesity and physical inactivity are common before and after a breast cancer diagnosis.
Mortality from Cancer According to BMI for U.S. Women in the Cancer Prevention Study II Calle, E. et al. N Engl J Med 2003;348:1625-1638
Mortality from Cancer According to BMI for U.S. Men in the Cancer Prevention Study II Calle, E. et al. N Engl J Med 2003;348:1625-1638
Meta-analysis Evaluating Measures of Adiposity at Diagnosis and Prognosis Recurrence at 5 yrs Death at 10 yrs HR [95% CI] HR [95% CI] Body Weight 1.78[1.50-2.11] 1.36[1.19-1.55] BMI 1.91[1.52-2.40] 1.60[1.38-1.76] Goodwin, P.. In: Psychosomatic Obstetrics and Gynecology, Bitzer J. and Stauber M. (Eds); Monduzzi Editore, International Proceedings Division, Bologna (Italy), p491-496, 1995.
Weight and Survival in Early-Stage Breast Cancer Estimated Relative Risk of Adverse Event 0 5 10 15 Distant Recurrence, p=0.0005 Death, p=0.0007 20 25 30 35 40 45 50 55 BMI (kg/m 2 ) Goodwin et al, JCO 2002
Post-Diagnosis Weight Gain and Breast Cancer Death in Women with BMI < 25 at diagnosis 2 P trend <.01 1.5 HR 1 0.5 0 Breast Cancer Death Maintain Gain < 2.0 kg/m2 Gain > 2.0 kg/m2 Kroenke C JCO 2005
In Population Studies, Overweight/Obesity Affects Breast Cancer Prognosis in: Premenopausal patients Postmenopausal patients Patients diagnosed with any disease stage Patients treated with any combination of surgery, radiation, systemic chemotherapy Cheblowski, Aiello, McTiernan JCO 2002;20(4):1128-1143
4 Changes in Exercise Frequency across the Colon Cancer Experience (N = 130) 3 Sessions Per week 2 1 Moderate Strenuous 0 Prediagnosis Active Treatment Post Treatment Courneya K and Friedenreich C. J Altern Complem Med 1997
Exercise Patterns across the Colon Cancer Experience (N = 130) 40 35 30 % 25 20 15 10 5 0 Maintainers Temporary Relapsers Permanent Relapsers Nonexercisers Adopters Courneya K and Friedenreich C. J Altern Complem Med 1997
Physical Activity Before and After Diagnosis in Breast Cancer Survivors The HEAL Study 3.5 3 P<.05 P<.05 P<.05 Hours/wee 2.5 2 1.5 1 Before Diagnosis After Diagnosis 0.5 0 In situ Stage I Stage II-IIIa Stage Irwin M. et al. Cancer 2003;97:1746-57
Physical Activity across the Breast Cancer Experience by BMI (HEAL Study, N = 547) 4 3 Hrs/week 2 1 0 Year Before Diagnosis Within 1st Year Post- Diagnosis Within 3rd Year Post- Diagnosis Irwin ML et al MSSE 2004 BMI < 25 BMI: 25-29.9 BMI > 30
Weight Change from Baseline to 2 yrs by change in PA (N = 544) 2.5 2 kg kg 1.5 1 * 0.5 0 0 < 90 min/wk 90-149 min/wk 150+ min/wk Irwin ML et al. JCO, 2005
Benefits of Increasing Post-Diagnosis PA Need to encourage cancer survivors to maintain (if active prior to diagnosis) or increase PA after diagnosis. PA is associated with numerous benefits Decreasing adverse side effects of surgery and treatment Improving quality of life and fatigue Improving fitness, functional capacity, and body composition Decreasing serum hormones and growth factors Improving cancer-specific survival and all cause survival
Physical Activity and Increased Survival in Breast Cancer Survivors More than four observational studies have examined the relationship between post-diagnosis physical activity and mortality after breast cancer diagnosis. 40-67% reduced risk with 2-3 hr/wk of moderate-intensity exercise Associations stronger in women with higher disease stage Holmes M et al JAMA 2005; Holick C et al. CEBP 2008; Pierce J et al JCO 2007; Irwin ML et al JCO, 2008.
Nurses Health Study: Physical activity after breast cancer diagnosis HR 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 P =.05 P=.004 P =.003 Recurrence BRCA Death Total Death MET-hr/wk MET-Hrs/week <3 3-8.9 9-14.9 15-23.9 Holmes *p=0.05, M et al JAMA # p<0.004 2005
Multivariable-Adjusted Relative Risk of Breast Cancer Death According to 2 Physical Activity Categories After Breast Cancer Diagnosis* Holmes, M. D. et al. JAMA 2005;293:2479-2486.
The HEAL Study: Physical Activity after Diagnosis Hazard Ratio for Death 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 P =.46 BC Death P =.04 Total Death MET-hr/wk 0 >0-9 9+ Irwin ML et al JCO, 2008.
Women s Health Initiative (WHI) WHI enrolled healthy postmenopausal women and collected physical activity information at least every 3 years. ~5430 women developed breast cancer while enrolled in WHI. Pre- and Post-diagnosis PA and other lifestyle and prognostic information were collected prospectively. Irwin, Chlebowski, McTiernan et al.
Post-diagnosis Physical Activity and Colorectal Cancer Survival: NHS Findings Meyerhardt, J. A. et al. J Clin Oncol; 24:3527-3534 2006
NHS and Change in Physical Activity Meyerhardt, J. A. et al. J Clin Oncol; 24:3527-3534 2006
The Women s Interventional Nutrition Study (WINS) Randomized 2400 women with early-stage breast cancer to low-fat diet intervention or control group Intervention involved oneon-one meetings with dietician, cooking classes WINS diet: reduce fat to 15% of total calories Chlebowski et al. JNCI, 2006.
Results by hormonal subtype ER Negative ER Positive Chlebowski, JNCI 2006
The Women s Healthy Eating and Living Study (WHEL) Included 3088 women with earlystage breast cancer Randomized to phone-based diet intervention or control WHEL Diet: High fruits and vegetables Low fat High fiber Pierce, Lancet 2007
Impact of Dietary Intervention on DFS Pierce et al., Lancet 2007.
Survival after WHEL Study enrollment by four diet and physical activity categories Pierce, J. P. et al. J Clin Oncol; 25:2345-2351 2007 Copyright American Society of Clinical Oncology
Insulin and breast cancer prognosis N Hormone Results Goodwin 512 Insulin 2-fold risk of recurrence and 3-fold risk of death in highest vs. lowest quartile Irwin 608 C-peptide 3-fold risk of breast cancer death in top tertile vs. bottom tertile 3.5-fold risk of breast cancer death for women with type 2 diabetes vs. bottom tertile (low c-peptide and no diabetes) Goodwin et al. JCO 2001;20:42-51; Irwin ML, et al. Under review
Insulin and Breast Cancer Prognosis 3.5 3 Hazard Rat 2.5 2 1.5 1 0.5 p = 0.007 p = 0.0001 Distant Recurrence Death 0 8.1-27 27-35.3 35.3-51.9 > 51.9 Insulin Quartiles (pmol/l) Goodwin et al. JCO 2001;20:42-51
C-Peptide and Breast Cancer Death Hazard Ratio 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 p = 0.0048 < 1.7 1.7-2.5 > 2.5 T2D C-Peptide Tertiles (ng/ml) Breast Cancer Death Irwin ML, et al. Under Review
Sex Steroids Modification of sex steroid levels has long been a mainstay of cancer therapy Early treatment for breast cancer included removal of ovaries, adrenals, and other endocrine organs More recently, aromatase inhibitors, which lower estradiol levels to below detectable levels of most assays, have been shown to significantly improve prognosis and lower risk of second breast cancers
Estrogen Levels by BMI in 505 Postmenopausal Breast Cancer Patients 30 25 pg/m 20 15 10 P trend = 0.005 Estrone Estradiol 5 P trend = 0.002 0 < 22 22-25 25-27.5 27.5-30 > 30 kg/m 2 McTiernan et al. J. Clin. Oncol. 2003;21:1961-66
Testosterone Levels by BMI in 505 Postmenopausal Breast Cancer Patient pg/m 200 180 160 140 120 100 80 60 40 20 0 P trend = 0.0001 < 22 22-25 25-27.5 27.5-30 > 30 Testosterone kg/m 2 McTiernan et al. J. Clin. Oncol. 2003;21:1961-66
Risk of Breast Cancer Death by Adiponectin (HEAL, 566 Stage I-IIIa patients, followed up mean 6 years) 1.2 1 P=0.08 Hazard Rat 0.8 0.6 0.4 0.2 0 Tertile 1 Tertile 2 Tertile 3 Adiponectin Duggan C, et al. To be submitted
2.5 2 Risk of Total Death by CRP (HEAL, 734 Stage 0-IIIa patients, followed up mean 6 years) P for trend=0.01 Hazard Rat 1.5 1 <1.2 mg/l 1.3-3.8 mg/l > 3.8 mg/l 0.5 0 CRP tertiles Pierce, et al. JCO, In Press
Interventions to Increase Physical Activity levels in Cancer Survivors Growing number of exercise interventions conducted pre-surgery, during treatment, and post-treatment treatment Numerous benefits associated with exercise.
Future Research Directions Need more studies of lifestyle and survival in other cancers More exercise and weight loss trials with novel endpoints Common side effects of treatment Inflammation Cell proliferation Disease-free survival
Conclusions Increasing PA after diagnosis is associated with a decreased risk of breast cancer mortality and all cause mortality Especially among women who are inactive prior to diagnosis! More research is needed on how to maintain weight and increase physical activity after a cancer diagnosis.
HEAL Study Acknowledgements Rachel Ballard-Barbash Barbash,, NCI Anne McTiernan,, FHCRC Leslie Bernstein, COH Rick Baumgarter,, Louisville WHI Study Rowan Chlebowski,, UCLA Anne McTiernan,, FHCRC