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The Population Impact of Endometrial Cancer Less stress, less food (and less processed food) and more walking Monika Janda Cancer of the uterus 5th most common cancer in women in Australia 16 per 100,000 women affected 85% are Type 1 cancers (low grade endometrial adenocarcinoma of endometriod cell type) AIHW, Cancer in Australia an overview 2010 Risk factors Lifestyle seems to play an important role GLOBOCAN 2008 http://globocan.iarc.fr Pathway between obesity and endometrial cancer An Modified based on : Calle EE, Kaaks R. Overweight, obesity and cancer. Nat Rev Cancer 2004;4(8):579-91 Rising Obesity rates in Australia... Source: Australian Bureau of Statistics. Australian Health Survey: First Results, 2011-2012 Lynch B. Cancer Epidemiology, Biomarkers, Prevention, 2010. Effect of exercise on arteries Green D, 2009. Exerc. Sport Sci. Rev. Effect of diet on metabolism • ANECS: High glycaemic index increases the risk of endometrial cancer Prevalence of overweight/obesity in Australia BMI category Normal (≤24.99) 45% Overweight (25.00-29.99) 31% 55% Obese (≥30.00-34.99) 24% AIHW: Diabetes prevalence in Australia. Diabetes series No 12; 2009 Among participants of the Laparoscopic approach to treatment of endometrial cancer (LACE) trial TLH (N=407) TAH (N=353) 63 (10) 63 (11) n(%) n(%) Normal (18.50-24.99) 47 (12) 46 (14) Overweight (25.00-29.99) 98 (25) 72 (21) Obesity class I (30.00-34.99) 77 (20) 87 (26) Obesity class II (35.00-39.99) 81 (21) 61 (18) Obesity class III (≥40) 86 (22) 74 (22) Age in years, mean(SD) BMI category† > 23% > 60% Comorbidity burden/medications n BMI >25 Hypertension Hyperlipidaemia Diabetes mell. Number of medications 0 1-4 5-9 10-14 % 635 391 192 168 n 87.3 53.8 26.3 23.1 % 130 389 187 21 Type of medications n Antihypertensives 609 Analgetics and antiinflammation 353 Lipid-Lowering agents 216 Diuretics 212 Antidiabetics 200 17.9 53.5 25.7 2.9 % 83.5 48.4 29.6 29.0 27.3 Cause of death in early stage endometrial cancer K.K. Ward et al. / Gynecologic Oncology 126 (2012) 176–179 Reduction of cancer risk by half Willett WC, Colditz GA, Mueller NE. Scientific America 1996; Lifestyle Risk Factors Lifestyle interventions A. Prevent endometrial cancer B. Part of treatment for endometrial cancer C. Supportive care after treatment for endometrial cancer Lifestyle interventions in patients at risk of diabetes and CVD • Diabetes Intervention trial: weight loss of ≥ 7% leads to reduction of diabetes incidence by 58% • PREMIER trial reduced rate of hypertension from 38% to 12% in lifestyle advice and diet group • Coronary Health Improvement project reduced nutrient intake and depression Merrill RM, et al. Nutrition 2008; Appel LJ et al. JAMA 2003; Knowler WC et al New Engl J Med 2002 Prevention - lifestyle Author Target group Intervention Outcomes Limitations/Barriers Campbell TP. Med Sci 115 obese sedentary 12 month aerobic Sports Exercise 2009 women exercise Weight loss 1.8kg, significant change in CRP, Interleukin 6 Yeon JY. Prev Med 2012 22 overweight women High vegetable fruit diet Interleukin 1 and 6 reduced Lim SS. Nutr Metabl &Cardiovascular 2009 Hoeger KM. Fertility Sterility 2004 203 women BMI av 33.2 12 weeks Metformin, Lifestyle lost 3kgs placebo or lifestyle more weight 38 overweight/obses 48 weeks of Combined group women with PCOS metformin ± lifestyle achieved 7-10% or placebo weight loss 39% attrition Friedenreich CM. Int J Obesity 2011 320 postmenopausal 12 months of aerobic Intervention women women exercise 5-times a lost average 10-17% week weight and body fat Control participants exercised as well Ricanati, Nutrition & Metabolism 2011 429 participants with Lifestyle 180 chronic conditions, program Significant loss in weight and improvement in various biomarkers Small study 48% attrition in lifestyle arm These weight loss drugs are great, have you tried them? Drugs or lifestyle? 203 young women, mean BMI 33.2 Lim et al. 2011, Nutr, Matobil. &Cariovascular Disease. Alpha Trial • Enrolled 320 postmenopausal women, BMI 22-40kg/m2., mean age 61 • Randomised to 12 months of aerobic exercise for 12 month • Significant decrease Total and abdominal fat Total and free estradiol Circulating insulin • Significant increase in SHBG Friedenreich CM et al, J Clin Oncol 2010, Endocr Relat Cancer 2011, Int J Obesity 2011, Cancer Causes Control 2011 Did they also randomise you to exercise? However • Most studies assessed intermediate outcomes • Only one study assessed impact of weight loss on endometrial cancer risk and found 4% risk reduction RR=0.96, 95% CI 0.61-1.52 (Parker) • Three studies assessed impact of physcial actvivity 38% to 46% decrease in risk (Moradi, Schouten, Terry) Parker ED, et al.Int J Obes Relat Metab Disord. 2003; Moradi T, et al. Cancer Causes Control, 2000. Schouten L et al. J Natl Cancer Inst, 2004; Terry P Int J Cancer, 1999 Pilot-trial for endometrial cancer survivors • 45 EC survivors, BMI >25 • 6 month weight loss and physical intervention • Aim to lose 5% of body weight, and increase physical activity to >3.5 hours/week • Based on Social Cognitive Theory • 85% of patients rated it helpful • Adherence rate to exercise and diet intervention was 73% Van Gruenigen el al. Gynecologic Oncology 109 (2008) 19–26 SUCCEED Trial Usual care group gained 1.5 Intervention group lost 3 Other benefits • Intervention group exercised 100min more per week • Ate about 200 kcal less per day • Ate 0.91 more servings of fruit or vegies • Strong evidence for risk increased trough overweight, obesity and lack of physical activity • Renehan, World cancer fund What will the scientist write down if I play dead? Identify patient and triage according to current symptoms Needs specialized evaluation Needs no special evaluation Breast Cancer Rehabilitation Education: risk reduction for treatmentrelated morbidities, uptake and/or maintenance of healthy lifestyle behaviors Evaluation and Prospective surveillance: evaluation of baseline health and fitness and commencement of prospective surveillance of treatment-related morbidities amenable to efficacious interventions (e.g., lymphedema, fatigue, cardiovascular disease late effect) Exercise Prescription: individualized based on woman’s knowledge (related to education) and previous exercise history and outcomes from evaluation and prospective surveillance Referral to specific allied health professional for evaluation and treatment as needed Hayes and Schmitz 2012 Needs no further special evaluation Recent High level of provision More frequent Time since diagnosis Distant Education Low level of provision Less Frequency of prospective surveillance frequent for treatment morbidities Exercise Prescription Medically-based Exercise setting Community-based Clinical exercise physiologist) Training of professional prescribing exercise Community fitness trainer Every session supervised Level of exercise supervision Unsupervised Unstable, complicated and/or multiple Presence of morbidities Allied health professionals (e.g., PT, OT, None, generally healthy Proposed breast cancer rehabilitation model which integrates surveillance, prevention education and management of treatment-associated morbidity and exercise prescription What? Follow a hunter/gatherers lifestyle: • Regular and extensive exercise • Eating plenty of fruits, vegetables and whole grains • Low intake of animal fats, red meat, refined starches • Minimal (no) alcohol How • Increase other behaviours (drinking water, moving) • Reduce some behaviours (sitting, eating) – Remove the trigger that leads to the undesirable behavior – Reduce ability to perform the behavior (make it harder to do) – Replace motivation for doing the behavior with de-motivator Source: behaviorwizard.org – Increase the number of triggers leading to the desirable behavior – Enhance ability to perform the behavior (make it easier to do) – Amplify motivation for doing the behavior with intrinsic and extrinsic motivators Other important considerations • • • • Psychological and psychosocial wellbeing Values Self-efficacy Social support The perfect balance Lewis Perrin and Yee Leung Weight Loss pilots • Dietician counselling service at the Mater Hospital, Brisbane • Meal replacement therapy – average 15 weeks • 9 patients with EAC, BMI average 53 • Average weight loss = 19kg • Range 8-35kg or 9.9% of body weight • • • • • King Edward Hospital, Perth 7 Patients with EAC BMI ranged from 39-70 Weight loss for 3-10 weeks Average weight loss was 10kg Lifestyle intervention • Original plan: based on CanChange program (multiple health behaviour change program Hawkes et al 2013. JCO in press) • However, concern about funding and sustainability Weight watchers • • • • • • • evidence based, commercial program, offers both face to face and online support across Australia, point system allowing all foods to be eaten (although emphasis on healthy foods), can be easily integrated into a family environment, physical activity encouraged, suitable for people of all BMI’s , can be used lifelong Way forward • Ample data suggests physical activity and weight loss of ≥7% have strong biological effect • Enrolment, Adherence and Drop-out may be a problem • Flexible, individualised program to suit women’s preferences, daily activities and support systems • Use of existing commercial program • Face to face/ Telephone/web delivery • Results hopefully in 2015/16 Acknowledgements • • • • • • • • • • • • • • • • Funding: Cancer Australia 1044900 Associate Professor Anna Hawkes Professor Chen Chen Associate Professor Jane Armes Ms Orla McNally A/Prof James Nicklin Professor Jonathan Carter Doctor Martin Oehler A/Prof Lewis Perrin Doctor Michael Bunting Professor Michael Quinn Associate Professor Pamela T. Soliman Professor Val Gebski Doctor Yee Leung Ms Merran Williams Assoc Prof Christopher Strakosch