the population impact of endometrial cancer. less stress, less food (and less processed food) and...
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The Population Impact of Endometrial Cancer
Less stress, less food (and less processed food) and
more walkingMonika Janda
Cancer of the uterus5th 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
Modified based on : Calle EE, Kaaks R. Overweight, obesity and cancer. Nat Rev Cancer 2004;4(8):579-91
An
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)
Age in years, mean(SD) 63 (10) 63 (11)
BMI category† 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)
> 60%
> 23%
Comorbidity burden/medications n %
BMI >25 635 87.3Hypertension 391 53.8Hyperlipidaemia 192 26.3Diabetes mell. 168 23.1
Number of medications n %0 130 17.91-4 389 53.55-9 187 25.710-14 21 2.9
Type of medications n %Antihypertensives 609 83.5Analgetics and antiinflammation 353 48.4Lipid-Lowering agents 216 29.6Diuretics 212 29.0Antidiabetics 200 27.3
Cause of death in early stage endometrial cancer
K.K. Ward et al. / Gynecologic Oncology 126 (2012) 176–179
Willett WC, Colditz GA, Mueller NE. Scientific America 1996;
Reduction of cancer risk by half
Lifestyle Risk Factors
Lifestyle interventions
A. Prevent endometrial cancerB. Part of treatment for endometrial cancerC. 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
Author Target group Intervention Outcomes Limitations/Barriers
Campbell TP. Med Sci Sports Exercise 2009
115 obese sedentary women
12 month aerobic 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
Small study
Lim SS. Nutr Metabl &Cardiovascular 2009
203 women BMI av 33.2
12 weeks Metformin, placebo or lifestyle
Lifestyle lost 3kgs more weight
48% attrition in lifestyle arm
Hoeger KM. Fertility Sterility 2004
38 overweight/obses women with PCOS
48 weeks of metformin ± lifestyle or placebo
Combined group achieved 7-10% weight loss
39% attrition
Friedenreich CM. Int J Obesity 2011
320 postmenopausal women
12 months of aerobic exercise 5-times a week
Intervention women lost average 10-17% weight and body fat
Control participants exercised as well
Ricanati, Nutrition & Metabolism 2011
429 participants with chronic conditions,
Lifestyle 180 program
Significant loss in weight and improvement in various biomarkers
Prevention - lifestyle
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.
• Enrolled 320 postmenopausal women, BMI 22-40kg/m2., mean age 61
• Randomised to 12 months of aerobic exercise for 12 month
• Significant decreaseTotal and abdominal fatTotal and free estradiolCirculating 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
Alpha Trial
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
Intervention group lost 3
Usual care group gained 1.5
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
Education: risk reduction for treatment-related morbidities, uptake and/or maintenance of healthy lifestyle behaviors
Referral to specific allied health professional for evaluation and treatment as needed
Frequency of prospective surveillance for treatment morbidities
More frequent
Recent
Less frequent
DistantTime since diagnosis
Proposed breast cancer rehabilitation model which integrates surveillance, prevention education and management of treatment-associated morbidity and exercise prescription
High level of provision
Low level of provisionEducation
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
Needs no further special evaluation
Breast Cancer Rehabilitation
Medically-based Exercise setting Community-based
Allied health professionals (e.g., PT, OT, Clinical exercise physiologist)
Every session supervised
Training of professional
prescribing exercise
Community fitness trainer
UnsupervisedLevel of exercise supervision
Unstable, complicated and/or multiple
Presence of morbidities
None, generally healthy
Exercise Prescription
Hayes and Schmitz 2012
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
• 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
• Increase other behaviours (drinking water, moving)– 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
Source: behaviorwizard.org
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