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

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Breast cancer incidence trends in developed & developing countries

Bray et al Breast Cancer Research 6: 229, 2004

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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

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513 400 310

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(N=33,660 women - 1987 breast cancers)

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(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