making a difference: how to reduce cancer occurrence and ... · how to reduce cancer occurrence and...

Making a Difference:

How to Reduce Cancer

Occurrence and Reoccurrence

W E N D Y D E M AR K - WAH N E F R I E D , P H D , R D

P R O F E S S O R AN D W E B B C H AI R O F N U T R I T I O N S C I E N C E S

AS S O C I AT E D I R E C T O R O F C AN C E R P R E V E N T I O N & C O N T R O L

U N I V E R S I T Y O F AL AB A M A AT B I R M I N G H AM

W O R K I N G E V E R Y D A Y T O P R O V I D E T H E H I G H E S T Q U A L I T Y O F L I F E F O R P E O P L E W I T H C A N C E R

Objectives

By the end of this presentation, the observer should be able to…

• Recognize trends in cancer prevalence, mortality and survivorship.

• Identify diet and physical activity guidelines for

healthy people and cancer survivors, and outline

the rationale that supports them.

• Identify sources of credible information

Each Year over 14 Million People are Diagnosed with Cancer

Over 8 Million Die from Cancer

Incidence in Males:

205/100,000

Incidence in Females:

165/100,000

Roughly 33 Million Cancer Survivors Worldwide

Over 827,090 in UK

GLOBOCAN 2012 (IARC) Section of Cancer Surveillance (13/4/2015)

Lung

Lung

Lung

Colorectal

Breast

Prostate

Stomach

Bladder Esophagus

Liver Cervix

Other

http://www-dep.iarc.fr/

Cancer-Related Diet & Physical Activity

Recommendations

Rock et al. CA Cancer J Clin 2012; WCRF-AICR 2nd Expert Research Report, http://www.aicr.org

WCRF- AICR (2007) American Cancer Society (2012)

Weight Be as lean as possible without

becoming underweight

Achieve & maintain a healthy weight

Physical

Activity (PA)

Regular PA, >30 min/day Avoid inactivity; PA >150/week;

strength training 2 x week

Dietary

Pattern

Avoid sugary drinks. Limit

energy-dense foods (foods high

in sugar & fat, and low in fiber)

Eat more of a variety of

vegetables, fruits, whole grains

and legumes

Limit consumption of

processed & red meat

Diet High F&V & Whole Grains

• Choose foods & beverages in

amounts that achieve & maintain a

healthy weight

• Eat > 2.5 cups fruits & vegetables/day

• Whole vs. refined grains

• Limit consumption of processed & red

meat

Other Limit salty foods -

Alcohol If drink limit to 1-2 drinks/day If drink limit to 1-2 drinks/day

Supplements Do not use supplements to

protect against cancer

BMI 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

Height Body Weight (pounds)

4’10 91 96 100 105 110 115 119 124 129 134 138 143 148 153 158 162 167

4’11 94 99 104 109 114 119 124 128 133 138 143 148 153 158 163 168 173

5’0 97 102 107 112 118 123 128 133 138 143 148 153 158 163 168 174 179

5’1 100 106 111 116 122 127 132 137 143 148 153 158 164 169 174 180 185

5’2 104 109 115 120 126 131 136 142 147 153 158 164 169 175 180 186 191

5’3 107 113 118 124 130 135 141 146 152 158 163 169 175 180 186 191 197

5’4 110 116 122 128 134 140 145 151 157 163 169 174 180 186 192 197 204

5’5 114 120 126 132 138 144 150 156 162 168 174 180 186 192 198 204 210

5’6 118 124 130 136 142 148 155 161 167 173 179 186 192 198 204 210 216

5’7 121 127 134 140 146 153 159 166 172 178 185 191 198 204 211 217 223

5’8 125 131 138 144 151 158 164 171 177 184 190 197 203 210 216 223 230

5’9 128 135 142 149 155 162 169 176 182 189 196 203 209 216 223 230 236

5’10 132 139 146 153 160 167 174 181 188 195 202 209 216 222 229 236 243

5’11 136 143 150 157 165 172 179 186 193 200 208 215 222 229 236 243 250

6’0 140 147 154 162 169 177 184 191 199 206 213 221 228 235 242 250 258

6’1 144 151 159 166 174 182 189 197 204 212 219 227 235 242 250 257 265

6’2 148 155 163 171 179 186 194 202 210 218 225 233 241 249 256 264 272

Normal Weight Overweight Obese

Worldwide rates of obesity and overweight

• Worldwide 35% of adults are overweight and 11% are obese (2008)

doubled since 1980 – prevalence higher in select survivor groups

(breast & prostate)

• 65% of the world's population live in countries where overweight and

obesity kills more people than underweight.

• Medical costs for obese people are $1,429 (USD) higher than those

of normal weight

Energy Restriction Prolongs Lifespan in Animal

Models

(80% of ad libitum for studies on cows and dogs and 60% for remaining species)

Lif

esp

an

(ye

ars

)

Hertford

Cow

Labrador

Retriever

F344

Rat

Sprague-

Dawley Rat

P53 -/-

Mouse

P53 +/+

Mouse

C3B10 RF1

Mouse

Hursting SD et al. Ann Rev Med. 2003

Increases in Cancer Risk with Overweight & Obesity

WHO: IARC 2002/WCRF AICR 2007/Polednak Cancer Detect Prev 2008, Larsson & Wolk BJ Cancer 2007; Zhao et al J Int Med Res 2012

Probable Evidence that Ovarian Cancer also is Weight-Related

% In

cre

ase in

Re

lative

Ris

k

Breast Colon Endometrium Kidney Esophagus Pancreas Thyroid Gallbladder

(post-meno)

0

50

100

150

200

250

Overweight Obesity

Does Intentional Weight Loss Curtail Risk?

1.

0

1.4 0.8 0.6 1.2 0.0 0.2 0.4

• 0.81

Breast Cancer

• 0.91

Colon Cancer

• 0.96

Endometrial Cancer

• 0.96

Obesity-Related Cancers: Breast, colon, endometrial & kidney

Similar data Miyagi Cohort (>10,000 Japanese women) - Kawai et al. Br. J Cancer Sept 2010 Parker et al. Intl J Obes Relat Metab Dis 27: 1447-52, 2003

0 7 6 5 4 3 2 1 8

Prostate (> 35)

Multiple Myeloma (> 35)

Gallbladder (> 30)

Bowel (> 35)

Esophagus (> 30)

Stomach (> 35)

Pancreas (> 35)

Liver (> 35)

NHL (> 35)

All cancers (> 40)

Kidney (> 35)

1.34

1.49

1.52

1.70

1.71

1.76

1.84

1.91

1.94

2.61 4.52

0 7 6 5 4 3 2 1 8 9 11 10

Multiple myeloma (> 35)

Bowel (> 35)

Breast (> 40)

Gallbladder (> 30)

Esophagus (> 30) Pancreas (> 40)

Cervical (> 35) Kidney (> 40)

Uterus (Womb) (> 40)

Liver (> 35) All cancers (> 40)

NHL (> 35)

Ovarian (> 35) 1.44 1.46

1.51

1.68

1.88 1.95

2.12

2.13 2.64

2.76 3.20

4.75 6.25

Relative Risk of Death (95% confidence interval)

Obesity and Cancer-related Mortality

Females

Males

Calle EE et al. NEJM.348:1625, 2003.

Prognostic Effects of Weight Gain Among Individuals

with Breast and Prostate Cancer:

Results of 2 Meta-Analyses

Group

(year)

# of

studies

Sample Relative Risk for every 5 kg/m2

increase in BMI from pre- to

post-dx

Chan et

al. (2014)

82 213,075 women

with breast cancer

Breast CA Specific Mortality

29% Higher

Total Mortality

8% Higher

Cao & Ma

(2011)

6 cohort 18,203 men with

prostate cancer

Biochemical Recurrence (PSA)

21% Higher

Prostate CA Specific Mortality

20% Higher

Linear dose–response meta-analysis of BMI and total mortality

Chan D S M et al. Ann Oncol 2014;annonc.mdu042

© The Author 2014. Published by Oxford University Press on behalf of the European Society for

Medical Oncology.

Potential Mechanisms Whereby

Obesity Influences Cancer

Obesity Cancer

Adipokines/Growth Factors

Inflammation

Sex Steroids

Insulin

Increased Substrate Levels

(glucose & free fatty acids)

Diabetes other Comorbidities

Binding Proteins/Receptors

Metformin, Statins and Other

Pharmacologic Agents Adapted from Irwin et al.

Weight Loss Interventions

• 1st trial de Waard 102 post-menopausal breast cancer survivors Europ J Cancer Prev 2:233, 1993

• 17 weight loss trials in breast cancer (2-18 months). No adverse events. 57% resulted in >5% loss of body weight. Clinically significant benefits in HbA1C, insulin, inflammatory markers, QoL, lipids, physical functioning and B/P with 5-9% weight loss.

• In field or in analysis SUCCESS-C pre/post breast cancer (n=1,400-1,600) 2-yrs, telephone counseling + mailed materials vs. mailed materials

DIANA-5 pre/post breast cancer (n=1,417) 5-yrs, clinic-based vs. mailed materials

ENERGY pre/post menopausal (N=692), Clinic based+ telephone counseling + mailed materials vs. standard care

Reeves M et al. Obesity Rev doi 10.1111/obr/12190 2014; Goodwin JCO 2014; Thompson HJ 2012

Effective Behavioral Strategies to

Promote Weight Loss

• Set a Goal

• Weigh everyday

• Self-monitor (record calories, exercise and weight)

• Stimulus Control

- prepackaged food

- not bringing high calorie, tempting foods home/hiding them

- avoidance of hunger

- maintaining distance

• Rule Making

- salad dressing on the side

- taking the stairs

Interest in Obesity & Cancer Increasing

IOM Workshop on Cancer Survival and Recurrence Oct 2011

2014 Nov 1;32(31):3568-74


Recommendations






Physical

Activity (PA)



Dietary

Pattern






and legumes






healthy weight




meat





Exercise • Systematic reviews, consensus reports & studies in

interim suggest exercise is safe & has consistent positive effects on…

- vigor/vitality

- cardiorespiratory fitness

- quality of life

- depression

- anxiety

- fatigue

• Data are accumulating to suggest a protective effect for recurrence and survival (i.e., CHALLENGE trial)

Exercise After Diagnosis & Association

with Recurrence & Mortality – Data from Cohort of 2987 Breast Cancer Survivors in Nurse’s Health Study

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

<3 3-8.9 9-14.9 15-23.9 24+

recurrence

breast cancer mortality

all cause mortality

Level of Exercise (MET hrs/week)

Holmes et al. JCO 20:2479-86, 2005

Re

lative

Ris

k

It takes a lot of exercise to burn just a

few Calories


Recommendations






Physical

Activity (PA)



Dietary

Pattern






and legumes






healthy weight




meat





Red Meat Consumption & Cancer–Related Mortality • Pooled analysis of 37,698 men from the Health Professionals Follow-up

Study and 83,644 women from the Nurses' Health Study

• 9464 cancer deaths during 2.96 million person-years of follow-up.

Q1

(ref)

Q2 Q3 Q4 Q5 P Trend HR (95% CI) for 1

svg day-1 increase

Total Red

Meat

1 1.05

0.98-1.12

1.09

1.02-1.16

1.16

1.08-1.24

1.19

1.11-1.28

<.001 1.10 (1.07-1.13)

Not

Processed

1 1.03

0.97-1.10

1.03

0.96-1.10

1.09

1.02-1.16

1.17

1.10-1.26

<.001 1.10 (1.06-1.14)

Processed 1 1.03

0.97-1.10

1.08

1.01-1.15

1.08

1.01-1.15

1.14

1.07-1.22

<.001 1.16 (1.09-1.23)

Pan A et al. Arch Intern Med March 12, 2012

• Study of Colorectal Cancer (CRC)-specific mortality in 2315 CRC Survivors

(HR, 1.79; 95% CI, 1.11 - 2.89) McCullough et al. J Clin Oncol 31:2773,2013

• 249 Melanoma Patients – those with weekly meat intake 1.84 95% CI 1.02-

3.30)

• s

Gould Rothberg et al. Cancer Epidemiol 30:599,2014

Dietary Patterns

Prudent vs. Western Team (year) Sample Diet CA Mortality

HR (95% CI)

Other Cause

Mortality

HR (95% CI)

Kroenke (2005) 2619 Breast

CA

Prudent 1.07 (0.66-1.73) 0.54 (0.31-0.95)

Western 1.01 (0.60-1.70) 2.31 (1.23-4.32)

Kwan (2009) 1901 Breast

CA

Prudent 0.79 (0.43-1.43) 0.35 (0.17-0.73)

Western 1.20 (0.62-2.32) 2.15 (0.97-4.77)

Vrieling (2013) 2522 Post-

menopausal

Breast

Prudent 0.89 (0.59-1.35) 0.81 (0.40-1.61)

Western 3.69 (1.66-8.17) 0.99 (0.64-1.52)

Meyerhardt

(2007)

1009 Stage

III CRC

Prudent

1.13 (0.77-1.67)

1.32 (0.86-2.04)

Western 2.85 (1.75-4.63) 2.32 (1.36-3.96)

Diet Quality: 3-of-4 studies show significant protective effect for overall mortality,

one shows significant protection for cancer specific mortality (George 2011 & 2014;

Izano 2013; Kim 2011)

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&docid=hz-NJ2XDRnEoqM&tbnid=60kkg9zUhjyUIM:&ved=0CAcQjRw&url=http://www.precisionnutrition.com/diet-and-adhd&ei=1B0kVMHPGIaSgwTNpICQCw&bvm=bv.76247554,d.eXY&psig=AFQjCNFBMdmXTvvCed6VRgH-KGdhephemw&ust=1411739461397999

Women’s Healthy Eating & Living

(WHEL) Study

Pierce JP et al. JAMA 298: 289, 2007

• Sample: 3088 early stage breast cancer survivors dx’d within 4 yrs

• Intervention: 5 vegetable servings plus 16 oz of vegetable juice; 3 fruit servings; 30 g of fiber; and 15% to 20% of energy intake from fat

• Follow-up: Up to 10 years

Intervention Control

Total Breast Cancer Events 256 262

Total Breast Cancer Deaths 127 135

Total Deaths 155 160

Pierce JP et al. JAMA 298: 289, 2007

0

5

10

15

20

25

All Patients ER positive ER negative

Low Fat Diet

Regular Diet

Results of the Women’s Intervention Nutrition Study (WINS) Show Reduced Rates of Recurrence in Patients Assigned to a Low Fat Diet (n=2,437)

Chlebowski et al. JNCI 98:1767, 2006

P =.034 P =.277

P =.018

Recu

rren

ce R

ate

s (

% o

f p

op

ula

tio

n)

Why the Discrepancy?

WINS WHEL

Time since

Diagnosis

Within 1-year Within 5-years

Sample Post-Menopause Pre/Peri/Post

Menopause

Screen for

Previous Diet

Yes No (baseline F&V

intake 7.4

servings/day)

Other Factors Lost 6 pounds

over study period

Weight stable

Functional Foods

Whole foods and

fortified, enriched, or

enhanced foods have a

potentially beneficial

effect on health when

consumed as part of a

varied diet on a regular

basis Academy of Nutrition & Dietetics

Soy

Tomatoes

Flaxseed

Broccoli

Garlic

Berries

Tumeric

Green tea

Red wine

Examples of Functional Foods Associated with Cancer Protection


Recommendations






Physical

Activity (PA)



Dietary

Pattern






and legumes






healthy weight




meat





Alcohol

• Direct association with cancers of the kidney, head and neck and primary risk of breast cancer (“no amount of alcohol is safe”

• If you are a survivor of head and neck cancer you should not drink alcohol since it will increase your chance complication and reduce survival

• If you are a survivor of other cancers the choice is less clear – it may increase your risk of recurrence (breast cancer) but also decrease your risk of death due to cardiovascular disease


Recommendations






Physical

Activity (PA)



Dietary

Pattern






and legumes






healthy weight




meat





Abbreviated History of Dietary

Supplements on Cancer

• Several cell culture & animal studies showing a benefit of various single nutrients and foods

• ATBC & CARET trials shows show increased risk of lung cancer in b-carotene arms

• Meta-analyses show significantly higher mortality with vitamin E & b-carotene

• Results of SELECT indicate no benefit of vitamin E & selenium for prostate cancer, suggestion that vitamin E linked with slightly increased risk and selenium linked with higher risk of diabetes Lippman et al. JAMA 2009)

• Results of NIH-AARP (n=295,344) show increased risk of fatal prostate cancer among men taking >7 multi-vitamins/week (RR: 1.98; 95% CI:1.07-3.66) Lawson et al. (2007)

Why have Supplement Trials Failed?

• Few have screened participants to assure marginal nutrient intakes (e.g., Linxian trial: ß-carotene, selenium, and a tocopherol gastric and esophageal cancer [Wang et al. CEBP 1994]).

• Chronic intake over a long period perhaps more predictive of risk. Several studies including WHEL show baseline intake and nutritional status more predictive of risk (Rock et al. CEBP 2009).

• Mononutrient supplements = monotherapy?

• Rush to test in Phase III before appropriate groundwork (need to determine appropriate isomer, dose, need for stepped trials)

Vegetables & Lung Cancer

Prospective Cohort Studies

0 0.5 1 1.5 2

Relative Risk

Steinmetz, 1994

Pietinen, 1999

Voorrips, 2000- Men

Voorrips, 2000-Women

Michels, 2000

Terry, 2001

Thun, 1992- Men

Thun, 1992- Women

Beta Carotene Supplementation & Lung Cancer

ATBC Current Smoker

Physicians’ Health

Never Smoker

Former Smoker

Current Smoker

CARET

Former Smoker

Current Smoker

0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2

When we try to pick out

anything by itself, we find

it hitched to everything in

the universe – John Muir

Bairati et al. JNCI ;97:481-8, 2005

Cancer-free survival (no recurrence & no SPT among participants randomly assigned to the

supplement arm (solid line) or to the placebo arm (dotted line)

Second Primary HR 2.88 (95%CI 1.56-5.31)

RCT of a- Tocopherol + b-Carotene vs. Placebo (52M median follow-up)

540 Cases w/ Stage I/II Head & Neck Squamous Cell Cancer

Bottom Line on Supplements

Rely on Food as a Source of Nutrients But , if considering supplements

-Have dietitian analyze diet for deficiency

- Check blood levels of nutrients

- Consider lowest dosage & most complex preparation

- If currently on supplements wean off slowly.

Calcium V.S.

Miracle

in a

Bottle

Synergy between Lifestyle Practices?

• 670 Early stage breast cancer survivors in Multi-ethnic Cohort

Inactive survivors eating poor-quality diets vs. Active survivors

eating better-quality diets had an 89% reduced risk of death

from any cause HR: 0.11 (0.04-0.36) and a 91% reduced risk of

death from breast cancer HR: 0.09 (0.01- 0.89). George et al. 2011

• 1490 early stage breast cancer survivors who ate 5+ daily

servings of F&V and who were active (540+ MET-min/w) had a

doubling of survival HR: 0.56 (0.31 - 0.98) Pierce et al. 2007

• 2193 post-menopausal breast cancer survivors in Iowa

Woman’s Health Study, those who adhered to 6-8 AICR/WCRF

guidelines vs. 0-4 had a 33% lower mortality rate Inoue-Choi et al. 2013

Additional Resources

• Scottish Cancer Prevention Network: http://www.cancerpreventionscotland.org.uk

• Cancer Research UK: http://www.cancerresearchuk.org

• World Cancer Research Fund: http://www.dietandcancerreport.org

http://www.cancerpreventionscotland.org.uk/

http://www.cancerresearchuk.org/

http://www.dietandcancerreport.org/

Great Research being done in Scotland

Annie Anderson, BSc PhD RD FRCP (Edin)

BeWEL Diet and Exercise intervention

Implemented with National Colorectal

Screening Program resulted in 3.5 kg loss

over 12 months with significant reductions

in blood pressure and glucose (Anderson AS et al. BMJ 2014)

Nanette Mutrie, PhD

Research “Sit less and walk more” in breast cancer

and other populations at risk

…..And many more

And many others

Conclusions:

Much Evidence that Diet and Exercise are

Important for Cancer Survivors

…but Much Work Needed

Bellizzi et al. JCO 2005; Blanchard JCO 2008, Courneya et al. CANCER 2008

• 52.8-71% Overweight or Obese

• 80.9-85.2% Eat <5 servings/day of Fruits and Vegetables

• 52.7-70.4% Underactive

• 8.4-17.4% Currently Smoke

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http%3A%2F%2Fwww.thegloss.com%2F2011%2F05%2F05%2Fodds-and-ends%2Fconfessions-of-a-non-exerciser%2F&ei=s2JSVeKnKarIsAS0u4GABw&psig=AFQjCNEwmvQJJLrUO9cuAGY4IcqE0JzQQw&ust=1431548945251265

Thank you! Questions?

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