Breast Cancer: Weight and Exercise Anne McTiernan, MD, PhD Fred Hutchinson Cancer Research Center Seattle, WA
Associations of Obesity with Overall & Breast Cancer Specific Survival
Survival Obese vs. Non-obese Breast Cancer Patients by Hormone Receptor Niraula et al. BCRT 2012;134:769-81
Survival Obese vs. Non-obese Breast Cancer Patients by Menopausal Status Niraula et al. BCRT 2012;134:769-81
Breast Cancer Specific Survival Obese vs. Non-obese Breast Cancer Patients by Hormone Receptor Niraula et al. BCRT 2012;134:769-81
Breast Cancer Specific Survival Obese vs. Non-obese Breast Cancer Patients by Menopausal Status Niraula et al. BCRT 2012;134:769-81
HEAL Cohort 1183 newly diagnosed breast cancer patients 3 centers: FHCRC, New Mexico, Los Angeles Population-based (registries) Multi-ethnic Followed for ~ 10 years post-diagnosis Assessing effect on prognosis of: weight, physical activity, metabolic hormones, inflammation, sex hormones, nutrition, vitamin D
BMI and Risk of Death, HEAL Cohort of Breast Cancer Patients, N=645, Followed Mean 8.5 Years Smith et al, submitted.
BMI & Recurrence: Non-inflammatory Locally Advanced and Inflammatory: MD Anderson (N=602) Dawood S et al. Clin Cancer Res 2008;14:1718-1725 2008 by American Association for Cancer Research
Obesity & Treatments
Obesity in N 0, ER+ Breast Cancer: Tamoxifen Efficacy
Survival by BMI: Neoadjuvant Breast Cancer Patients MD Anderson Series Litton, J. K. et al. J Clin Oncol; 26:4072-4077 2008 Copyright American Society of Clinical Oncology
BMI in node-positive breast cancer patients treated with docetaxel and doxorubicin-containing adjuvant chemotherapy: BIG 02-98 trial, N=2,887 A: overall survival B: disease-free survival de Azambuja et al. Br Ca Res Treat 2009
Overweight/obese by Treatment (tamoxifen, anastrozole) & Survival: ABCSG-12 Trial (n=1803) Pfeiler G et al. JCO 2011;29:2653-2659 2011 by American Society of Clinical Oncology
Hazard Plots for Anastrozole vs Tamoxifen by BMI: All & Distant Recurrences Sestak I et al. JCO 2010;28:3411-3415 2010 by American Society of Clinical Oncology
Weight Change after Diagnosis and Breast Cancer Prognosis 4/8 studies: significant decreased survival/ increased recurrence with weight gain Nurses Health Study, n=5204, followed ~ 9 years, risk or death for BMI gain in non-smokers: 0.5-2.0 kg/m 2 : 1.35 > 2.0 kg/m 2 : 1.64 LACE cohort, stage 1-3, n=1689, followed ~ 7 years Weight loss > 10%: 2.5 x increased risk of death in ER- /PR- patients Chlebowski, Aiello, McTiernan JCO 2002;20(4):1128-1143 Kroenke et al. J. Clin Onc 2005;23(7):1370-8. Caan B et al. Ca Causes Cont 2008:19:1319 1328
Other Potential Adverse Effects of Obesity in Breast Cancer Wound complications Lymphedema Radiation therapy challenges? Endometrial cancer in tamoxifen users Congestive heart failure in patients treated with doxorubicin Increased risk for coronary disease, diabetes, stroke, hypertension, osteoarthritis, several cancers, decreased quality of life
Weight & Prognosis: Summary Overweight/obese/underweight prognosis Weight gain after diagnosis Purposeful weight loss after diagnosis???
Weight & Prognosis: Summary Weight effects seen in: Pre-menopausal Postmenopausal All stages Hormone receptor positive & negative Varied treatments including surgery, chemotherapy, hormonal agents Population & clinical trial cohorts Cheblowski, Aiello, McTiernan JCO 2002;20(4):1128-1143 Niraula et al. BCRT 2012;134:769-81
Potential Mechanisms of Obesity- Prognosis Link Estrogens, androgens Hyper-insulinemia, insulin resistance, diabetes, pre-diabetes Inflammatory markers Diet/physical activity
Hazard Ratio Risk of Breast Cancer Death by C-peptide (HEAL, 571 stage I-IIIa patients, followed up mean 4.1 years) 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 C-peptide P trend = 0.03 Irwin et al. J Clin Oncol 2011; 29(1):47-53 < 1.7 ng/ml 1.7-2.5 ng/ml > 2.5 ng/ml Diabetics
Risk of Death by C-Reactive Protein (HEAL, 734 stage I-IIIa patients, followed up mean 3.8 years) 2.5 P trend =0.01 Hazard Ratio 2 1.5 1 0.5 < 1.2 mg/l 1.3-3.8 mg/l > 3.9 mg/l 0 Met-hr/wk Pierce et al. J Clin Oncol 2009; 27(21):3437-44.
HEAL Study Weight Change (kg) in 2 Years after Diagnosis, by Stage 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 P=0.004 Stage in situ Stage I Stage II-IIIa Irwin, M. L. et al. J Clin Oncol; 23:774-782 2005
Fasting Glucose and Breast Cancer Outcomes Population: 512 early stage breast cancer no known diabetes Results: Quartile DDFS OS Mean Range HR (adjusted)* (95% CI) HR (adjusted)* (95% CI) 4.5 3.5-4.7 1 1 4.9 4.7-5.1 1.28 (1.02-1.60) 1.26 (0.93-1.70) 5.2 5.1-5.4 1.50 (1.04-2.17) 1.46 (0.89-2.40) 5.7 5.4-11.6 1.88 (1.06-3.35) 1.81 (0.83-3.93) p=0.027 unadjusted p=0.034 adjusted p=0.036 unadjusted p=0.014 adjusted * adjusted for age, T, N, grade, hormone receptor, chemotherapy, hormone therapy Goodwin PJ et al. J Clin Oncol 2012
Low-Fat Diet and Breast Cancer Prognosis: the WINS Study Clinical trial 2,437 women with early stage breast cancer Recruited from 37 U.S. sites 48-79 years old Randomly assigned to low-fat diet or control group 6 lb. greater weight loss at 12 mos. in intervention vs. control women Followed for up to 5 years Risk of death was significantly reduced by 24 percent in diet patients vs. controls
High Vegetable/Lower Fat Diet: the WHEL Study Multi-site clinical trial 3088 women with early stage breast cancer 18-70 years old Randomly assigned to high vegetable/fruit/fiber, low-fat diet or control group Followed for a mean 7.3 years Little change in diet vs. control diets No effect of diet on prognosis Pierce et al. JAMA. 2007 Jul 18;298(3):289-98.
Alcohol & Breast Cancer Prognosis Recent findings suggest alcohol use (> 1 drink/d) associated with: Increased recurrence Increased contralateral/2 nd primary breast cancer Moderate alcohol use may be associated with reduced mortality Li et al. JCO 2009;27:5312-5318. Kwan et al. JCO 2010;28(29):4410-6. Barnett et al. JCO 2008; 26:3310-6.
Physical Activity & Breast Cancer Survival Ballard-Barbash R, et al. JNCI Jun 6;104(11):815-40
Other Exercise Effects in Survivors 10-16 week aerobic exercise program results in: Improved fitness Moderate weight and fat loss Increased lean mass Reduced fatigue Improved mood Improved overall quality of life Galvao et al. JCO 2005;23:899-909 (review)
Total Physical Activity Before and After Diagnosis in Breast Cancer Survivors by Treatment (HEAL) Hours/week 20 19.5 19 18.5 18 17.5 17 16.5 16 15.5 15 P<.05 Surgery Surgery + Radiation Treatment P<.05 Surgery + Chemo Irwin M. et al. Cancer 2003;97:1746-57 Before Diagnosis After Diagnosis
Treatments Available for Conditions (None FDA Approved for Breast Cancer) Reduce/treat obesity: Reduced calorie diet Physical activity Weight loss therapies (extreme obesity or co-morbidities Xenical/Alli (orlistat, blocks fat absorption prescription & OTC) Qsymia (topiramate, an anti-convulsant & phentermine, an appetite suppressant) Belviq (lorcaserin hydrochloride, activates serotonin 2C receptor) Bariatric surgery Note: all for adding to diet & exercise weight loss program Medications to treat obesity mediators: Excess insulin (Metformin - NCIC trial ongoing) Inflammation (Statins, NSAIDS)
Implementing Lifestyle Change Reduced calorie (~ 1200-1800 kcal/day) Increased physical activity (>150 minutes/week moderate intensity) Strength training does not increase lymphedema (progress slowly) Weekly meetings with counselor Self-monitoring: Daily diet logs all foods and drinks Weighing at least weekly Daily exercise logs - recreational/walking activity Goal 7%-10% weight loss in 6 months Studies in breast cancer survivors show lower weight loss than in persons without cancer
Conclusions: Clinical Guidelines During chemo/radiation: Avoid weight gain unless underweight Exercise as tolerated: start slowly, increase slowly After or no chemo/radiation: Lose weight if BMI > 25.0 through calorie reduction + increased physical activity Aerobic exercise at least 30 min/day, 5 days/wk Gradually increase to moderate intensity (e.g. brisk walking, biking, fast dancing) Long-term survivors: weight loss may lower estrogens, beneficial for patients who have completed hormone therapy Keep alcohol to 1 drink/day or less