Diet & exercise & breast cancer Mary Pegington Research Dietitian Genesis Prevention Centre & Nightingale Breast Screening Centre, University Hospital of South Manchester
Dec 26, 2015
Diet & exercise & breast cancer
Mary Pegington Research Dietitian
Genesis Prevention Centre &Nightingale Breast Screening Centre,
University Hospital of South Manchester
Breast cancer rates are increasing1-2% per year
2011 : 50,285 cases / year
Breast cancer incidence trends
Bray et al Breast Cancer Research 6: 229, 2004
Europe120
100
80
70
60
50
40
30
20
10
1960 1970 1980 1990 2000Year
Ag
e st
and
ard
ised
rat
e (w
orl
d)
Americas120
100
80
70
60
50
40
30
20
10
1960 1970 1980 1990 2000Year
Ag
e st
and
ard
ised
rat
e (w
orl
d)
Asia/Oceania120
100
80
70
60
50
40
30
20
10
1960 1970 1980 1990 2000Year
Ag
e st
and
ard
ised
rat
e (w
orl
d)
UK
FINLAND
SPAIN
SLOVAKIA
USA
CANADA
PUERTO RICO
COLUMBIA
AUSTRALIA
JAPAN
INDIA
Western lifestyle & breast cancer risk
loss orgain 2.0
gain2.1-10.0
gain10.1-20.0
gain>20.0
Weight gain (kg)
Mul
tivar
iate
RR
Adult weight gain increases risk of post menopausal breast cancer
1.01.2
1.6
2.0
0
0.5
1
1.5
2
Huang et al JAMA 287: 1407, 1997, Colditz GA et al Arch Int Med 122: 481, 1995
loss orgain 2.0
gain2.1-10.0
gain10.1-20.0
gain>20.0
Weight gain (kg)
Mul
tivar
iate
RR
Adult weight gain increases risk of post menopausal breast cancer
1.01.2
1.6
2.0
0
0.5
1
1.5
2
12 Diabetes
3 Cardiovascular
disease
Huang et al JAMA 287: 1407, 1997, Colditz GA et al Arch Int Med 122: 481, 1995 Willett W et al JAMA 273: 461, 1995Aleksandrova K et al Eur J Cancer. 2013 49:3526-36.
1.5 Colorectal
cancer
Weight loss reduces breast cancer incidence
Cohort studies Population Weight loss RR
Harvie et al2005
34,000 postmenopausal women
>5% ~3.5 kg
0.61 (0.46 – 0.80)
Eliassen et al2006
87,000 postmenopausal women
>10kg ~ 15%
0.43 (0.25 – 0.86)
Prentice et al2006
48,835 postmenopausal women
2 kg ~3%
0.91 (0.83 – 1.01)
Teras et al2011
Bariatric surgery
13,055 overweight & obese postmenopausal women
>5 kg ~7%
0.78 (0.55 – 1.10)
Obesity and Cancer
Hursting SD & Hursting MJ Arterioscle Thomb Vasc Biol 32: 1766, 2012
Premenopausal weight is important
• Excess weight increases risk age >35yrs
- General population (Peacock et al Am J Epidemiol. 1999)
- Family History (Cecchini et al Cancer Prev Res 2012)
• Pre menopausal weight gain increases postmenopausal risk
UK data shows 10/12 kg of adult weight gain occurs by age of 50
(Health Survey England 2012)
Exercise & breast cancer
• Each hour of exercise/ week reduces risk of breast cancer by 6%
• Aim for 3 hours of exercise / week
Friedenreich Recent Results Cancer Res. 2011;188:125-39
-27%
-24%
-18%
<1%
<22
22-24.9
25-29.9
>30
Friedenreich Recent Results Cancer Res. 2011;188:125-39.
BC risk reduction
BMI
“Fit and Fat” does not protect against breast cancer
Alcohol
10 units / week vs. no drinking increases BC risk by 10%
BUT
No alcohol increases risk of heart disease by 40%
No alcohol increases risk of dying from any cause by 13%
Lowest risk for dying from any cause with 3–15 g/day
Higher risk for dying from any cause with >60 g/day
Ronksley P E et al. BMJ 2011;342:bmj.d671
Recommended Mediterranean diet
Weight control and energy restriction after diagnosis
Niraula S et al Breast Cancer Res Treat. 2012 134:769-81
Obesity & overall survival
Obesity & breast cancer survival
20% more likely to die from any cause
26% more likely to die from breast cancer
Weight gain after diagnosis
• 60 - 75% of patients gain weight after diagnosis
• Most weight gained during first year
• Weight gain persists - long term problem
• Greatest weight gain in:
premenopausal, adjuvant chemotherapy,
thinner women, chemotherapy induced menopause
Dietary interventions - RCT WINS – 1994-2004 WHEL 1995 - 2006
N 2437 3088
Age 48 – 79 18 - 70
Time post diagnosis Up to 1 year Up to 4 years
Intervention 5 years
Sustained fat reduction 20% vs 29%
6 years Transient fat reduction
20% vs 29%12 vs 6 fruit & veg / day
Weight change- kg -2.7 vs + 0.7 +0.5 vs +0.4
Disease free survival
0.76 (0.6 – 0.98) 0.96 (0.8 – 1.14)
Kwan ML et al CEBP 2013 22(1): 32–41.
Trend for increased alcohol & reduced overall mortality & cardiovascular mortality
Alcohol after diagnosis
2.5 hours of moderate activity /week & outcome (n = 13,302)
Recurrence Breast cancer mortality
All cause mortality
Normal weight 0.93 (0.81 – 1.07)
0.72 (0.61 – 0.86)
0.72 (0.63 – 0.83)
Overweight 0.98 (0.85 – 1.14)
0.78 (0.65 – 0.94)
0.69(0.59 – 0.81)
Obese 0.96 (0.77 – 1.19)
0.72 (0.61 – 0.86)
0.86(0.7 – 1.06)
Beasley et al Breast Cancer Res Treat 2012 ; 131 : 637 - 643
Calorie restriction is difficult to achieve and maintain in humans!
• 25-30% adherence to low cal diets at 12 months
• 20%-40 achieve > 5% weight loss at 1 year
• Only 20% of our women at high risk of breast cancer maintain > 5% weight loss at 5 years
Dansinger et al . JAMA 2005;293:43-53.
Our first intermittent study RCT of IER vs. daily restriction 2006-2009
1. Is intermittent energy restriction acceptable & easier to follow than daily restriction?
2. Does IER have better effects on risk markers for breast cancer, diabetes, CVD compared to daily restriction?
-8
-6
-4
-2
0
0 1 2 3 4
Chan
ge fr
omBa
selin
e M
ean
Months
WeightIECRICRDER
-6
-5
-4
-3
-2
-1
0
0 1 2 3 4
Chan
ge fr
om
Base
line
Mea
n
Months
Body FatIECRICRDER
Change in weight & body fat including drop outs (N = 115)
P<0.05
P<0.01
Intermittent diet study 2 -Summary
• IER superior to daily restriction for reducing body
fat and insulin.
• 1 day of restriction / week maintains weight loss
Intermittent diets may reduce chemotherapy toxicity
• Animal studies and case studies suggest IER may reduce chemotherapy toxicity
• May reduce oxidative stress & upregulate stress response mechanisms.
• B-AHEAD 2 will look at the effects on chemotherapy toxicity: self report data and two novel blood biomarkers
Safdie et al Aging (Albany NY) 2009 1:988-1007Lee et al Sci Transl Med 2012 7;4 (124)
B-AHEAD 2 Study
Outcomes 3 weeks post final chemotherapy• Weight, body fat (DXA), waist, hips• Breast cancer prognosis marker – insulin• Oxidative stress markers• Chemotherapy toxicity (self report & Cytokeratin 18 & FMS Like Tyrosine
Kinase 3 ligand markers)• CVD risk parameters: lipids, blood pressure • Fitness, Quality of life, Dietary intake, Physical activity
n = 170Scheduled to receive adjuvant or neoadjuvant chemotherapy
2 day / week IER (& exercise)Individual advice and telephone support
Group 1: n = 85
Group 2: n = 85
Daily energy restricted diet (& exercise)Individual advice and telephone support
4 ½ to 6 months of chemotherapy
Acknowledgements
FAMILY HISTORY CLINIC/PROCAS
Tony HowellGareth EvansPaula StavrinosLouise DonnellyR GreenhalghJenny AffenJayne Beesley
LIFESTYLE
Michelle HarvieMary PegingtonDebbie McMullenKath Sellers Ellen MitchellPam CoatesLesley CoatesCheryl BarlowNina BrogdenGenesis Volunteers
FUNDING
Genesis Breast Cancer PreventionNational Institute of Health ResearchBreast Cancer CampaignWCRFBreast Cancer Research Trust
Rob Clarke – Patterson InstituteKath Spence – Patterson InstituteAndy Sims – Breakthrough EdinburghRoy Goodacre - UOMMark Mattson – NIH Baltimore
COLLABORATORS
The Patients
Any questions?