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Transcript
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
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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