Preventing breast cancer and its recurrence with diet and exercise

1. 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

2. 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

3. Breast cancer rates 1975 -2005- UK screening 140 Incidence Mortality 120 100 80 Rate per 100,000 population 60 40 20 0 1975 1978 1981 1984 1987 1990 1993 1996 1999 2002 2005 Year of Diagnosis/death

4. Breast cancer incidence trends in developed & developing countries Americas Asia/Oceania Europe 120 120 120 USA 100 100 100 CANADA UK 80 80 AUSTRALIA 80 FINLAND 70 70 70 60 60 60 PUERTO RICO SPAIN 50 50 50 40 40 40 SLOVAKIA COLUMBIA JAPAN Age standardised rate (world) Age standardised rate (world) Age standardised rate (world) 30 30 30 INDIA 20 20 20 10 10 10 2000 2000 2000 1970 1980 1990 1970 1980 1990 1960 1960 1970 1980 1990 1960 Year Year Year Bray et al Breast Cancer Research 6: 229, 2004

5. 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

6. Population study :Iowa Women’s Health Study (N=33,660 women - 1987 breast cancers) Gained 5% body wt (age 30-50yrs) (1.0) 1.0 Stable Lost 5% body wt (0.78) (0.61) Relative risk 0.5 0 513 400 310 BC incidence 100,000 women yrs Harvie M ,HowellA et al CBEP 14: 656, 2005

7. 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

8. 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 ?

9. CER 7 days ~1500 kcal / day Mediterranean diet IER 2 days ~550kcal: 2 pints semi-skimmed milk 1 portion fruit 4 portions vegetable 2 pints low-calorie drinks Multi-vitamin & mineral 5 days ~1900 kcal/day Mediterranean diet

10. Main findings • 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

11. 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

12. After diagnosis of breast cancer • 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 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.

13. 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

14. Developments which may arise from work • 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

15. Collaborators Prof Anthony Howell Prof Gareth Evans Prof Nigel Bundred Dr Sue Astley/ Alan Hufton Dr Penny Hopwood Dr Rob Clarke /Dr Kai Ren Ong Dr Andrew Wardley Prof 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