The Population Impact of Endometrial Cancer. Less stress, less food (and less processed food) and more walking Monika Janda.

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