Preventing breast cancer and its recurrence with diet and exercise
Dr Michelle Harvie Transforming Knowledge: Closing the
Research Evidence-Practice Gap.
April 29th /30th 2009
• Breast Cancer Prevention
The Genesis Prevention Centre
Breast cancer rates in UK and worldwide
The potential role of diet and exercise for prevention
Our prevention research
• After diagnosis The importance of lifestyle after diagnosis
Our research amongst breast cancer patients
• Developments which may arise from work
Breast cancer rates 1975 -2005- UK
screening
0
20
40
60
80
100
120
140
1975
1978
1981
1984
1987
1990
1993
1996
1999
2002
2005
Year of Diagnosis/death
Rat
e p
er 1
00,0
00 p
op
ula
tio
n Incidence Mortality
Breast cancer incidence trends in developed & developing countries
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
Our Prevention Research
• Epidemiology: assessing risk/ protective factors from population studies ( Iowa Women’s Health Study)
• Designing and testing optimum diets to prevent cancer (randomised trials) Intermittent energy restriction
• How does diet weight control reduce risk ? Small mechanistic studies
• Qualitative research to understand behavioural & psychosocial factors which influence adherence to diet and exercise recommendations amongst high risk women
Population study :Iowa Women’s Health Study
1.0
513 400 310
Rel
ativ
e ris
k
(1.0)
(N=33,660 women - 1987 breast cancers)
0.5
0
(0.78) (0.61)
BC incidence 100,000 women yrs
Gained 5% body wt (age 30-50yrs)
Stable
Lost 5% body wt
Harvie M ,HowellA et al CBEP 14: 656, 2005
Our Prevention Research
• Epidemiology: assessing risk/ protective factors from population studies ( Iowa Women’s Health Study)
• Designing and testing optimum diets to prevent cancer (randomised trials) Intermittent energy restriction
• How does diet weight control reduce risk ? Small mechanistic studies
• Qualitative research to understand behavioural & psychosocial factors which influence adherence to diet and exercise recommendations amongst high risk women
RCT of intermittent vs. continuous energy restriction
Background
• ~ 60% of women overweight / obese
• Wt loss >5% difficult to achieve (50%) & maintain (20% over 5 years)
• Animal studies show intermittent restriction is superior to continuous restriction for breast cancer prevention
Questions
• Is intermittent energy restriction acceptable & easier to adhere to than daily (continuous) restriction ?
• Does intermittent restriction have greater beneficial effects on breast cancer risk markers compared to continuous restriction ?
CER
7 days
~1500 kcal / day Mediterranean diet
IER 2 days ~550kcal:
2 pints semi-skimmed milk1 portion fruit 4 portions vegetable2 pints low-calorie drinksMulti-vitamin & mineral
5 days~1900 kcal/day
Mediterranean diet
Main findings
1. IER is as effective as CER for weight loss but is not more acceptable or easy to adhere to
2. IER appears to have better effects on insulin sensitivity
Our Prevention Research
• Epidemiology: assessing risk/ protective factors from population studies ( Iowa Women’s Health Study)
• Designing and testing optimum diets to prevent cancer (randomised trials) Intermittent energy restriction
• How does diet weight control reduce risk ? Small mechanistic studies ( gene expression in breast tissue)
• Qualitative research to understand behavioural & psychosocial factors which influence adherence to diet and exercise recommendations amongst high risk women
• 60% of patients overweight / obese at diagnosis
• Obesity linked to breast cancer & overall mortality (RR ~1.5-2.5)
• Obesity in early breast cancer patients linked to:~50% more non cancer deaths ~60% more other cancers
• 75% of patients gain weight after diagnosis
• Weight gain worsens prognosis in 4/6 cohort studies
After diagnosis of breast cancer
Goodwin PJ. Energy balance and cancer prognosis: Breast Cancer In: McTiernan A. Cancer prevention & management through exercise &weight control. 2006. Dignam et al JNCI 2003 95:19 1467 Irwin et al J Clin Oncol. 2005 Feb 1;23(4):774-82.
B - AHEAD StudyBreast – Activity and Healthy Eating After Diagnosis
• Weight control amongst early breast cancer patients
• Randomised comparison of 3 diet & exercise programmes:
-Supervised
-Home based
-Leaflet only
• Recruiting 480 pt from UHSM, Christie, Oldham, N Manchester Stepping Hill August 2008 – Oct 2011
Developments which may arise from work 1. Acceptable effective energy restriction interventions could:
-Prevent the 25% of breast cancer cases attributable to excess calories.
-Prevent 25% of relapse amongst early breast cancer patients
2. Defining mechanism of cancer prevention with energy restriction could lead to :
-Energy restriction mimetic agents for cancer prevention
- Predictive test of breast cancer risk using genetic variation in key
enzymes up / down regulated with ER
Prof Anthony HowellProf Gareth EvansProf Nigel BundredDr Sue Astley/ Alan HuftonDr Penny HopwoodDr Rob Clarke /Dr Kai Ren OngDr Andrew WardleyProf Kinta Beaver
Dr Jack Cuzick Wolfson Institute London Dr Alan Flyvbjerg & Jan Frystk Aarhus Denmark
Dr Susan Jebb HNR MRC Cambridge
Prof Mark Mattson NIHR Institute of Ageing
Baltimore
Dr Alison Wearden University of Manchester
Dr Gaynor Parfitt University of Exeter
Collaborators