Diet & exercise & breast cancer

1. Diet & exercise & breast cancer Mary Pegington Research Dietitian Genesis Prevention Centre & Nightingale Breast Screening Centre, University Hospital of South Manchester

2. Breast cancer rates are increasing1-2% per year2011 : 50,285 cases / year

3. Breast cancer incidence trends Europe Americas Asia/Oceania 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

4. Western lifestyle & breast cancer risk

5. Adult weight gain increases risk of post menopausal breast cancer 2.0 2 1.6 1.5 1.2 1.0 Multivariate RR 1 0.5 0 gain >20.0 gain 2.1-10.0 gain 10.1-20.0 loss or gain 2.0 Weight gain (kg) Huang et al JAMA 287: 1407, 1997, Colditz GA et al Arch Int Med 122: 481, 1995

6. Adult weight gain increases risk of post menopausal breast cancer 12 Diabetes 2.0 3 Cardiovascular disease 2 1.6 1.5 1.2 1.5 Colorectal cancer 1.0 Multivariate RR 1 0.5 0 gain >20.0 gain 2.1-10.0 gain 10.1-20.0 loss or gain 2.0 Weight gain (kg) Huang et al JAMA 287: 1407, 1997, Colditz GA et al Arch Int Med 122: 481, 1995 Willett W et al JAMA 273: 461, 1995 Aleksandrova K et al Eur J Cancer. 2013 49:3526-36.

7. Weight loss reduces breast cancer incidence

8. Obesity and Cancer Hursting SD & Hursting MJ ArterioscleThombVascBiol 32: 1766, 2012

9. Premenopausal weight is important • Excess weight increases risk age >35yrs • - General population (Peacock et al Am J Epidemiol. 1999) • - Family History (Cecchiniet 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)

10. 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

11. “Fit and Fat” does not protect against breast cancer BMI BC risk reduction -27% <22 -24% 22-24.9 -18% 25-29.9 >30 <1% Friedenreich Recent Results Cancer Res. 2011;188:125-39.

12. 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

13. Recommended Mediterranean diet

14. Weight control and energy restriction after diagnosis

15. Obesity & breast cancer survival Obesity & overall survival 26% more likely to die from breast cancer 20% more likely to die from any cause Niraula S et al Breast Cancer Res Treat. 2012 134:769-81

16. 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

17. Dietary interventions - RCT

18. Alcohol after diagnosis Trend for increased alcohol & reduced overall mortality & cardiovascular mortality Kwan ML et al CEBP 2013 22(1): 32–41.

19. 2.5 hours of moderate activity /week & outcome (n = 13,302) Beasley et al Breast Cancer Res Treat 2012 ; 131 : 637 - 643

20. 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.

21. 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?

22. Change in weight & body fat including drop outs (N = 115) P<0.05 P<0.01

23. Intermittent diet study 2 -Summary • IER superior to daily restriction for reducing body fat and insulin. • 1 day of restriction / week maintains weight loss

24. Intermittent diets may reduce chemotherapy toxicity • Animal studies and case studies suggest IER may reduce chemotherapy toxicity • May reduce oxidative stress & upregulatestress 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 1:988-1007 Lee et al SciTransl Med 2012 7;4 (124)

25. B-AHEAD 2 Study n = 170 Scheduled to receive adjuvant or neoadjuvant chemotherapy Group 2: n = 85 Daily energy restricted diet (& exercise) Individual advice and telephone support Group 1: n = 85 2 day / week IER (& exercise) Individual advice and telephone support 4 ½ to 6 months of chemotherapy • 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

26. The Patients FAMILY HISTORY CLINIC/PROCAS LIFESTYLE COLLABORATORS Acknowledgements Michelle Harvie Mary Pegington Debbie McMullen Kath Sellers Ellen Mitchell Pam Coates Lesley Coates Cheryl Barlow Nina Brogden Genesis Volunteers Rob Clarke – Patterson Institute Kath Spence – Patterson Institute Andy Sims – Breakthrough Edinburgh Roy Goodacre - UOM Mark Mattson – NIH Baltimore Tony Howell Gareth Evans Paula Stavrinos Louise Donnelly R Greenhalgh Jenny Affen Jayne Beesley FUNDING Genesis Breast Cancer Prevention National Institute of Health Research Breast Cancer Campaign WCRF Breast Cancer Research Trust

27. Any questions?