Diet, Exercise, and Cancer Risk Diane Baer Wilson, EdD, MS, RD Associate Professor Division of Quality Healthcare Department of Internal Medicine Co-Director Cancer Prevention and Control Massey Cancer Center Virginia Commonwealth University I am delighted to be here to share a bit about the work I am doing in SC related to nutrition and cancer prevention. Have been involved in this area of research for the last five years when Dr Dan Nixon brought a focus on the role of nutrition in cancer when he arrived at MUSC. CCFellows2-13-06

Today’s objectives Examine dietary-related factors and physical activity related to cancer risk Discuss dietary fat as a model for dietary studies related to cancer risk Review nutrition measurement methods Examine recent research related to BMI and breast cancer

the trigger.” Elliott Joslyn, MD “Genes load the gun. Lifestyle pulls the trigger.” Elliott Joslyn, MD

11 11

Cancer risk factors Age Family history Hormone exposure …… …… …… …… …… …… Tobacco use Diet/exercise Environmental exposures Alcohol Intake

Cancer Risk Factors: Nutrition Top Issues: Energy Balance Weight Exercise Nutrient Composition Dietary Fat Fruit/Vegetables Fiber Soy

Understanding dietary fat/cancer hypotheses Nutrition relatively recent area of cancer research Research seeds: Correlational Animal research Cross sectional RCT

Fat intake/breast cancer, Carroll, 1975.

Dietary Fat/Breast Cancer Animal studies Proportionate level of tumor growth recorded in laboratory rats related to level of dietary fat fed animals over designated period of time. (1975-1980’s)

Dietary Fat/Breast Cancer Human studies Cross sectional Nurses Health Study-Willett, et al, 2000.

Dietary Fat/Breast Cancer Randomized Clinical Trial “Low-fat Dietary Patterns and Risk of Invasive Breast Cancer” The Women’s Health Initiative Randomized Controlled Dietary Modification Trial Prentice, Caan, Chlewbowski, et al. JAMA 2006;295: 629-642. (2/8/06)

Participant Flow in the Dietary Modification Component of the Women's Health Initiative Prentice, R. L. et al. JAMA 2006;295:629-642. Copyright restrictions may apply.

Baseline Demographics of Participants in Women's Health Initiative Dietary Modification Trial* Prentice, R. L. et al. JAMA 2006;295:629-642. Copyright restrictions may apply.

Nutrient Consumption Estimates and Body Weight at Baseline and Year 1 Prentice, R. L. et al. JAMA 2006;295:629-642. Copyright restrictions may apply.

Blood Biomarkers for Baseline and Year 3* Prentice, R. L. et al. JAMA 2006;295:629-642. Copyright restrictions may apply.

Risk of Invasive Breast Cancer and Other Major Clinical Outcomes Prentice, R. L. et al. JAMA 2006;295:629-642. Copyright restrictions may apply.

Breast Cancer Risk by Baseline Dietary Factors Prentice, R. L. et al. JAMA 2006;295:629-642. Copyright restrictions may apply.

Breast Cancer Risk Based on Baseline Demographics, Medical History, and Health Behavior Variables Prentice, R. L. et al. JAMA 2006;295:629-642. Copyright restrictions may apply.

The American view of nutrition information

Dietary Assessment Twenty-four hour dietary recall Food frequency questionnaire Diet record Diet history

Data Collection Methods 24 hour recall method Most common method used for national dietary surveys Information on everything consumed over past 24 hours-relies on memory Trained interviewers non-judgmental neutral

Food Record Method Detailed record of all foods consumed on one or more days at time consumed Less dependent on memory Face to face training on completeness and accuracy essential Accurate portion reporting essential Final record reviewed by professional

Food frequency questionnaires Food frequency surveys most common measurement method in nutrition epi research Average intake, “usual” intake Easy to complete Foods, clarity, format important

Approaches for Evaluating Dietary Questionnaires Compare mean of nutrient intake Proportion of intake accounted for Reproducibility Validity Compare to biochemical indicator Compare to physiologic indicator Ability to predict disease

Food Recalls/Records Foods Recalls and Records Based on specific foods consumed Attempt to get data on one’s “true intake”, open-ended Can be representative if enough days tested Best method for comparing intake to recommendations Most used to validate FFQ

Designing and Administering Questionnaires Motivated subjects Clear instructions Correct foods Standardized procedures Interview or telephone Portion sizes?

Determining best method Individual intake or group mean? Actual intake or relative ranking? Open-ended method or structured list? Age limitations? Literacy considerations?

Overweight and breast cancer Women who are overweight are more likely to: Develop breast cancer Be diagnosed at a later stage Have higher mortality rates

Overweight and Breast Cancer Review of 26 studies examining the association of pre-morbid weight or weight at diagnosis with recurrent disease or survival (Rock and Wahnefried, 2002) 17 found increased BMI significantly associated with increased risk of death 2 null findings 7 inverse findings

Overweight and Breast Cancer Weight gain and increased risk Obesity increases peptide hormones-insulin and steroid hormones-estrogen Heaviest women have 3x level of estrogen than lean women without HRT Obesity increases risk of death from breast cancer about as much as mammography reduces it.

Breast Cancer Survivorship With early diagnosis, the survival rate has significantly increased 22% of all cancer survivors are breast cancer survivors Breast cancer survivors comprise the largest proportion of cancer survivors Survival rate is lalargely due to diagnosis occurring at a local stage, associate with a 96% 5 year survival rate

Weight Gain Weight gain 60% of women report weight gain after diagnosis more prevalent: premenopausal at diagnosis received adjuvant chemotherapy in African Americans caloric intake

Reasons for weight gain: Likely to be at least “peri menopausal” Being told to “keep your strength up” during therapy Comfort foods Less exercise Needs more research….

Exercise Type of exercise Breast cancer Walking vs. more rigorous forms Breast cancer Multi beneficial Mental, physical, emotional Integration

Addressing weight gain in African American breast cancer survivors African American women have higher mortality from breast cancer when compared to Caucasian women Some 60% of all women report gaining weight after being diagnosed with breast cancer. However, African American women are especially at risk for this weight gain, after diagnosis of breast cancer, placing them at greater risk for cancer recurrence and shorter survival time.

Testing an exercise intervention in African American breast cancer survivors (Study 1) Study Aim: Determine the feasibility and impact of a cognitive, behavioral theory-based walking intervention, Walking Counts! in a sample of AA breast cancer survivors. Feasibility: Attendance, compliance, process measures Outcomes: Integration of regular exercise (steps/day) change in BMI, waist, hip, forearm circumferences, body fat %, blood pressure, attitude toward exercise and cancer stress.

Walking Counts!-Methods Eligibility: Breast cancer diagnosis >3 months past cancer treatment Mobile <70 years old Description of the intervention: Health Belief Model Eight week community-based, 75 minute sessions Benefits, barriers, relationship to cancer risk, Personal assessment/problem solving Pedometers, scheduling, and tracking of steps/day Wilson et al; Preventing Chronic Disease 2005

Walking Counts!-Results Feasibility Attendance-70% attended > 7 sessions Retention: 92% retained 1 dropped after enrollment due to scheduling 1 recurred Pedometers Steps only mode 25% needed replacement

Walking Counts!-Results Characteristics of the Sample (n=22) Age (yrs) 55 (39 – 66) Weight (lbs) 191 (142 – 271) BMI (kg/m2) 32.7 (25.2 – 47.2) Education: (%) < high school High school graduate Post high school 4.5 90.9 Marital Status: (%) Married Single/Divorced/Widowed 50

Characteristics of the Sample Menopausal Status (%) Pre Post 13.6 86.4 Time Since Diagnosis: (%) 1-6 years 7-10 years More than 10 years 59.1 27.3 Type of Treatment: (%) Chemotherapy Radiation therapy Both Neither 18.2 45.5 Tamoxifen: (%) Yes No 22.7 77.3 Alcohol: (%) Yes 72.7 Smoking: (%) Yes 9.1 90.9

Walking Counts! Pre/Post Measures Baseline (N=22) Change p value* Anthropometric measures: Steps/day 4791 +3506 <0.001 BMI (kg/m2) 32.7 - 0.38 0.004 Weight (lb.) 191.2 - 2.0 0.005 Body Fat (%) 40.1 - 3.4 0.003 Waist circumference (in.) 39.7 - 1.8 0.037 Hip circumference (in.) 47.2 - 0.87 0.020 Arm circumference (in.) 13.9 - 0.58 0.007 Systolic B/P (mm Hg) 140.9 - 10.1 0.000 Diastolic B/P(mm Hg) 80.1 - 6.2 0.005 Waist to Hip ratio 0.8 - 0.02 0.156 Attitudinal measures: Exercise Attitude Total 66.2 + 3.0 0.029 Cancer Stress Total 6.8 - 0.36 0.201 * Paired “t-test” for difference in group means.

Steps/day at Baseline, Post and 3 Month Post Intervention p<.001 B/P***, p=.001*** B/3mth

Other research addressing obesity Nutrigenomics: Studies to help understand the mechanism by which genes may influence chronic disease risk related to nutrients and obesity

Genes and obesity in breast cancer Study Aim: Measure breast cancer gene expression profiles and analyze differences in tumor gene expression according to ethnicity in lean (BMI <25) and overweight (BMI >30) women Methods: Using tissue samples taken at diagnosis of breast cancer, we will study microarray expression of selected genes in 100 AA and 100 Caucasian women. Co-variates, include menopausal status, serum markers for insulin resistance and obesity, dietary intake and level of physical activity Implications: Study results may help to identify molecular changes and or genetic pathways in lean vs overweight women that contribute to breast cancer outcomes. (O’Connell P, Penberthy L, Wilson DB, Dumur K)

Other dietary trials: Women’s Intervention Nutrition Study (WINS) Tests effect of low-fat intervention on recurrence in 2500 breast cancer survivors Women’s Healthy Eating and Living intervention 3,109 survivors tests increased fr/veg intake, low fat, high fiber on progression of disease

Other nutrition areas of interest:

Soy Dual roles-low vs high levels Food sources only Soy protein 25 g/day Isoflavones-genistein Avoid supplements

Omega-3 fatty acids Slow growth of tumors in animals May increase efficacy of chemopreventive agents Cold water fish- Variable even within fish types Flax seed Canola oil

Supplements Cancer patients start consuming more supplements and herbal products after diagnosis Health claims on labels are not all official terms Watch the research-many products are in trials

What to eat? Emphasize plant based foods Eat 5-10 servings of fruits/vegetables chemopreventive constituents fiber antioxidants Eat less red-meat Pay attention to type of fat Don’t eliminate fat Eat more fish

Summary Nutrient driven hypotheses have significant measurement threats to validity Providing the public with sound nutritional guidelines requires a thorough examination of “the evidence” The evidence for the role of obesity and that for the role of exercise are among the strongest for providing advice to the public Much more scientific research is needed to better understand the role of macro and micro nutrients related to specific cancer risk.

“Nutrition is one of the most significant determinants of health and one of the most modifiable.” The US Surgeon General