Optimal Nutritional Goals for

the Cancer Survivor

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

Disclosures

AFFILIATION/FINANCIAL

INTERESTS

(prior 12 months)

CORPORATE

ORGANIZATION

Grants/Research Support: No

Corporate

Sponsorship

Scientific Advisory

Board/Consultant:

Speakers Bureau:

Stock Shareholder:

Other

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

• Recognize trends in cancer prevalence, mortality and survivorship.

• Identify common issues in cancer survivorship.

• Identify diet and physical activity guidelines for

cancer survivorship and outline the rationale that

supports them.

• List some of the gaps in knowledge related to

nutrition and cancer survivorship

• Identify reliable sources for nutrition and cancer

information.

Number of Cancer Survivors is Steadily

Rising Good News!

14.5 M!

Cancer Survivors at greater risk

- Progressive disease

- Second primaries

- Cardiovascular Disease

- Diabetes

- Osteoporosis

- Sarcopenia

- Functional decline

Cancer Survivorship:

The Bad News

% with Limitations:

Survivors vs. General Population

Hewitt, Rowland, Yancik. J Gerontol. 58:82, 2003

Possible Solutions

Diet Exercise

Depression

Fatigue

Adverse Body Composition

Functional Decline

Comorbidity

Recurrence Growing evidence Growing evidence

Possible benefit Probable benefit Convincing benefit

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

Weight Management & Energy

Balance

Anorexia/Cachexia

• Patients with select respiratory,

G.I. & childhood cancers

• Patients living with advanced

cancer

• Increasing weight to desired

range important for recovery,

well-being, functional status

• Diet & exercise key roles +/-

pharmacotherapy

Overweight/Obesity

• Risk factors for several

cancers, as well as cancer-

related mortality

• Increased weight at diagnosis

is a poor prognostic factor

• Weight gain common during &

after treatment–linked with co-

morbidity, functional decline &

maybe recurrent/progressive

CA

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

Increases in Cancer Risk with Overweight & Obesity

0

20

40

60

80

100

120

140

160

Overweight Obesity

WHO: IARC 2002/WCRF –AICR 2007

Breast (post-menopause)

Colon Endometrium Kidney Pancreas Esophagus

Probable Evidence that Cancer of the Ovary & Gallbladder are Weight-Related

0 7 6 5 4 3 2 1 8

Prostate (> 35)

Multiple Myeloma (> 35)

Gallbladder (> 30)

Colon and rectum (> 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)

Colon and rectum (> 35)

Breast (> 40)

Gallbladder (> 30)

Esophagus (> 30) Pancreas (> 40)

Cervical (> 35) Kidney (> 40) Uterus (> 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 RR (95% CI) 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

1.29 (0.97-1.72)

Total Mortality

1.08 (1.01-1.15)

Cao & Ma

(2011)

6 cohort 18,203 men with

prostate cancer

Biochemical Recurrence

1.21 (1.11-1.31)

Prostate CA Specific Mortality

1.20 (0.99-1.46)

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

• 14 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

LISA 336 post menopausal, telephone counseling + mailed materials vs. mailed materials

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

Choice 259 post menopausal – low CHO vs. low fat vs. control

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

Interest in Obesity & Cancer Increasing

IOM Workshop on Cancer Survival and Recurrence Oct 2011

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

2012 American Cancer Society (ACS)

Nutrition & Physical Activity Guidelines for Cancer Survivors

Achieve and maintain a healthy weight

If overweight or obese, limit high calorie foods & beverages increase physical

activity to promote weight loss

Engage in regular physical activity

• Avoid inactivity; resume normal activities as soon as possible following dx

• Exercise >150 minutes/week

• Include strength training exercises at least 2 days/week

Achieve a dietary pattern that is high in vegetables, fruits and whole grains

• Follow ACS Guidelines on Nutrition & Physical Activity for Cancer Prevention

- Choose foods & beverages in amounts that achieve/maintain a healthy weight

- Limit processed and red meat

- Eat > 2.5 cups of vegetables & fruits/day

- Choose whole grains instead of refined grain products

- If you drink ETOH, drink <1 drink/day for ♀ & 2 drinks/day for ♂

Supplements

• Try to obtain nutrients through diet, first.

• Consider only if a nutrient deficiency is biochemically or clinically observed, or if

intakes fall persistently below recommended levels as assessed by an RD.

CA CANCER J CLIN (2012) DOI.10.3322/CAAC.21142 www.cacancerjounral.com

Cochrane Review: Exercise on Quality of Life Post-treatment

40 trials with 3694 participants Mishra et al. Cochrane Database Rev 2012

Outcome # studies/N Evidence Qual Positive effects

Overall QOL, <12 weeks 11/826 Low 0.48 (0.16-0.81)

Overall QOL, 6 mo 2/115 Moderate 0.46 (0.09-0.84)

Anxiety, <12 weeks 4/455 Low -0.26 (-0.4 to -0.07)

Emotional well being 8/632 Low 0.33 (0.05 to 0.61)

Fatigue, <12 weeks 10/745 Moderate -0.82 (-1.50 to -0.14)

Fatigue, 12 wks-6 mo 3/246 Low -0.42 (-0.83 to -0.02)

Pain, <12 weeks 4/289 Moderate -0.29 (-0.55 to -0.04)

Sexuality, 6 mo 2/193 Moderate 0.40 (-0.72 to -0.20)

Sleep disturbance, <12 weeks 8/438 Moderate -0.46 (-0.72 to -0.20)

Social functioning, <12 weeks 5/386 Very low 0.45 (0.02 to 0.87)

Social functioning, 6 months 2/110 Moderate 0.49 (0.11 to 0.87)

Forest plot of the relations of change in physical activity (PA) from

pre- to post-diagnosis to total mortality and cancer mortality.

Schmid D , and Leitzmann M F Ann Oncol 2014;25:1293-1311

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

Medical Oncology. All rights reserved. For permissions, please email:

journals.permissions@oup.com.

2012 American Cancer Society (ACS)

Nutrition & Physical Activity Guidelines for Cancer Survivors

Achieve and maintain a healthy weight

If overweight or obese, limit high calorie foods & beverages increase physical

activity to promote weight loss

Engage in regular physical activity

• Avoid inactivity; resume normal activities as soon as possible following dx

• Exercise >150 minutes/week

• Include strength training exercises at least 2 days/week

Achieve a dietary pattern that is high in vegetables, fruits and whole grains

• Follow ACS Guidelines on Nutrition & Physical Activity for Cancer Prevention

- Choose foods & beverages in amounts that achieve/maintain a healthy weight

- Limit processed and red meat

- Eat > 2.5 cups of vegetables & fruits/day

- Choose whole grains instead of refined grain products

- If you drink ETOH, drink <1 drink/day for ♀ & 2 drinks/day for ♂

Supplements

• Try to obtain nutrients through diet, first.

• Consider only if a nutrient deficiency is biochemically or clinically observed, or if

intakes fall persistently below recommended levels as assessed by an RD.

CA CANCER J CLIN (2012) DOI.10.3322/CAAC.21142 www.cacancerjounral.com

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)

• Substitution estimates of 1 serving/day of other foods (e.g., fish, poultry, nuts,

legumes, low-fat dairy, and whole grains) for 1 serving/day of red meat were

associated with a 7% to 19% lower mortality risk. Estimates suggest that

9.3% of deaths in men and 7.6% in women could have been prevented at

follow-up if there was a reduction in 0.5 servings/day (~42 g/day) of red meat.

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

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)

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

• Comments: No weight loss, baseline F&V ~ 7.4 servings/day

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)

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

Associations Between Alcohol-Use and

Second Primaries (Select Studies) Team (yr) Primary

CA

Sample Median

F/U

Results

HR (95%CI)

Lin et al.

(2005)

HNSCC 123 SPT in 1257

Cases

73M Daily Drinkers at dx

2.1 (1.4-3.3)

Trentham-

Dietz et al.

(2008)

Breast

CA 10,953 BCA cases

488 Breast SPT

132 CRC SPT

113 Endometrial SPT

36 Ovarian SPT

84M >7 drinks/wk 1-yr post-dx

1.09 (0.78-1.53)

1.92 (1.03-3.43)

0.84 (0.42-1.69)

0.55 (0.18-1.72)

Knight et al.

(2009)

Breast

CA

708 Asynchronous

contralateral BC vs.

1399 unilateral Ctrls

60M

(mean)

Ever Reg Drank 1.3 (1.0-1.6)

Post-dx Drinker 1.2 (0.9-1.5)

Do et al.

(2003)

HNSCC 201 SPT in 1181 pts in

13 cis RA RCT

12M Continued Drinking

1.3 (1.0-1.7)

Leon et al.

(2009)

HNSCC 257 MSPT vs. 257

matched Ctrls

48M vs

126M

Continued Drinking

5.2 (3.3-7.9)

Li et al.

(2009)

ER+

Breast

CA

365 Asynchronous

contralateral BC vs.

726 unilateral Ctrls

101M Current Drinker

1.9 (1.1-3.2)

2012 American Cancer Society (ACS)

Nutrition & Physical Activity Guidelines for Cancer Survivors

Achieve and maintain a healthy weight

If overweight or obese, limit high calorie foods & beverages increase physical

activity to promote weight loss

Engage in regular physical activity

• Avoid inactivity; resume normal activities as soon as possible following dx

• Exercise >150 minutes/week

• Include strength training exercises at least 2 days/week

Achieve a dietary pattern that is high in vegetables, fruits and whole grains

• Follow ACS Guidelines on Nutrition & Physical Activity for Cancer Prevention

- Choose foods & beverages in amounts that achieve/maintain a healthy weight

- Limit processed and red meat

- Eat > 2.5 cups of vegetables & fruits/day

- Choose whole grains instead of refined grain products

- If you drink ETOH, drink <1 drink/day for ♀ & 2 drinks/day for ♂

Supplements

• Try to obtain nutrients through diet, first.

• Consider only if a nutrient deficiency is biochemically or clinically observed, or if

intakes fall persistently below recommended levels as assessed by an RD.

CA CANCER J CLIN (2012) DOI.10.3322/CAAC.21142 www.cacancerjounral.com

Dietary Supplements & 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

• SELECT trial shows higher risk of prostate cancer with vitamin E and higher risk of diabetes with selenium.

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

• 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)

Mayne S T et al. Cancer Res 61:1457-63, 2001

RCT of b-Carotene (50 mg/d) vs. Placebo (51M median follow-up)

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

SPT or local recurrence, P = 0.59

HR = 0.69 (95%CI 0.39-1.35) SPT Head & Neck

HR = 1.44 (95%CI 0.62-3.39) SPT Lung

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?

• Early stage breast cancer survivors in Multi-ethnic Cohort (n=670) Compared with inactive survivors consuming poor-quality diets, survivors engaging in any physical activity and consuming 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)

• In 1490 early stage breast cancer survivors a combination of 5+ daily servings of F&V + accumulating 540+ MET-min/w associated with a doubling of survival HR: 0.56 (0.31 - 0.98) (Pierce et al. 2007)

• In 2193 post-menopausal breast cancer survivors from Iowa Woman’s Health Study those who were most adherent vs. least adherent (6-8 vs. 0-4) to AICR/WCRF guidelines had a 33% lower mortality rate (Inoue-Choi et al. 2013)

Rates of Overweight & Obesity among Cancer

Survivors:

Results of Two National Surveys

Overweight Obese Total

U.S. Survivors 37.0% 21.9% 58.9%

Canadian

Survivors

34.4% 18.4% 52.8%

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

Blanchard et al, JCO 2008.

Many cancer survivors do not adhere to recommendations

(ACS Cancer Survivors II Study, n=9,105)

More Research is Needed

• Optimal timing

• Specific content, sequencing

and dose

• Impact on array of outcomes

• Mechanisms of action

• Factors that moderate effect

(cancer-type, tumor

characteristics, treatment, age,

co-morbidity, gender, etc.)

• Optimal delivery channel

(dissemination)

• Cost-effectiveness

Resources

• American Cancer Society: www.cancer.org

• Academy of Nutrition and Dietetics: www.eatright.org

• American Institute for Cancer Research: www.aicr.org

• Centers for Disease Control: www.cdc.gov/HealthyLiving

• National Center for Complementary & Alternative Medicine: http://nccam.nih.gov

http://aspo.org

March 15-17th

Birmingham, AL

Interactive Poster Sessions on Obesity and E-cigarettes

Preconference Workshop: Underserved Cancer Survivors