Obesity is now clearly established as a major risk factor for endometrial cancer. In medium income country like ours , Obesity prevention and lifestyle initiatives should become the responsibility of public health services. Stepwise programmes with realistic time-related goals are required, starting with modification of lifestyle, progressing to pharmacotherapy and ultimately obesity surgery. The real challenge now is to triage those women at a higher risk and offer them prophylactic measures as COCPs ,DMPA, oral progesterone or Mirena coil. Standard treatment for endometrial cancer is surgery. Obesity is associated with numerous disorders which put the patient at increase risk of peri-operative complications that require more detailed pre-operative assessment and more intensive post-operative care. Thus treatment for endometrial cancer needs to be reassessed in the complex and increasingly common situation of the obese, older women with this disease.

1. Wafaa B. Basta
Specialist Gynaecology & Obstetrics at Mataria Teaching Hospital
MBBch., MSc., Egyptian Fellowship, MRCOG
ERC MEMBER
2nd Annual ERC-RCOG International Conference
Sonesta Cairo 3rd March 2012

2.  One of the most serious public health
problems of the 21st century.
 Obesity is a leading preventable cause
of death worldwide.

3. Genetics Behavior
Environment

4. a person’s weight in kilograms
square of height in metres
(kg/m2).

5. * <18.5 : Underweight
* 18.5-24.9 : Normal/Healthy
* 25.0-29.9 : Overweight (pre-obese)
* 30.0-34.9 : Obese (Class I)
* 35.0-39.9 : Obese (Class II)
* ≥40 Obese ( Class III = morbid obesity)
o Waist –hip ratio correlates more with the
metabolic disorder.
Obesity. Guidance on the prevention, identification, assessment and management of
overweight and obesity in adults and children. London: (NICE), 2006.

6.  In1997 : obesity is
a global epidemic.
 At 2008 : 1.5
billion individuals <
20 ys. are obese.
 Obesity rates are
rising worldwide.
Obesity: Preventing and managing the
global epidemic. Geneva : WHO , 2000.

7.  25% of adults in the UK are now obese .
 50% of women would be obese by 2050. ( if
no action were taken). [The Government
commissioned Foresight report 2007]
Statistics on Obesity, physical activity & diet :England 2010 in NHS
information centre for life style statistics 2010.

8.  About one-third of U.S. adults (33.8%) are
obese.
National Health & Nutrition Examination Survey (NHANES) 2007 -2008

9.  In 1992, mothers with young children had a
mean (BMI) of 26.9.
 By 2005, rise to a mean BMI of 30.1, with
nearly 50% of Egyptian women of reproductive
age classified as obese.
WHO study (Musaiger 2004) Demographic and Health
Surveys

11.  The most common cancer of the female
genital tract.
 The fourth most common cancer in women.
 5% of all female cancers in 2007. (ASR 19.4)
 1975 - 1993 : Incidence remained stable.
 1993 - 2007 : Incidence increased by <40% .
Cancer statistics registrations ; Registrations of cancer diagnosed in 2007 ,
England 2010, National statistics ,London

12.  Gharbia Population Based Cancer Registry 2002-
2003: Endometrial cancer is the 2nd Gynaelogical
cancer in female, 9th of all female cancers. (ASR
2.1%)
 Incidence of uterine cancer in urban areas is
almost 6 times higher than rural ones.
 Aswan Population Based Cancer Registry 2008:
Endometrial cancer is the 2nd Gynaelogical cancer
in female,6th of all female cancers. (ASR 4.1%)
ASR= Age Standardised Incidence Rate

13. No. 1
No.2
WHO/FAO, Joint WHO/FAO Expert Consultation on Diet, Nutrition
and the Prevention of Chronic Diseases, in WHO Technical Report
Series. 2003, WHO: Geneva

14. • Major studies confirmed that being overweight or
obese increases risk of various cancers.
 Esophagus
 Pancreas
 Colon and rectum
 Breast (after menopause)
 Endometrium
 Kidney
 Thyroid
 Gallbladder
Renehan, A.G., et al., Body-mass index and incidence of cancer: a systematic review and
meta-analysis of prospective observational studies. Lancet 2008. 371(569-578).

15.  Overweight and obesity are behind around
17,000 cases of cancer each year in the UK.
Parkin, M., et al., The fraction of cancer attributable to lifestyle and environmental factors
in the UK in 2010. BJC 2011. 105, Supp. 2, 6 December 2011

16.  In 2007 : 50,500 cancer in women (7 %) were
due to obesity.
 By 2030 : obesity will lead to about 500,000
additional cases of cancer in the USA.
NCI Surveillance, Epidemiology, and End Results (SEER) data,
2007 , United States

17.  Risk of endometrial cancer is increased in
women with a BMI greater than 30kg/m2
 The risk increases linearly with increasing
BMI.
 In the UK, approximately 50% of endometrial
cancers are attributable to obesity.
Reeves, G.K., et al., Cancer incidence & mortality in relation to BMI in the Million Women
Study: BMJ 2007

18.  Obese women are 3 to 4 times more likely to
develop endometrial cancer than people with
a healthy bodyweight ,regardless of
menopausal status.
Friedenreich, C., et al., Anthropometric factors and risk of endometrial cancer: the
European prospective investigation into cancer and nutrition. Cancer Causes Control, 2007

19.  Obesity is predominantly associated with
type1(endometroid) endometrial cancer, rather
than type 2 (non-endometroid type such as
serous or carcino-sarcoma).
 However, both subtypes are increased with
obesity.
McCulloiugh, M.L.,et al., body mass & endometrial cancer risk by HRT &
cancer subtypes. Cancer Epidemiol Biomarkers Prev,2008

21.  In pre-menopausal women:
obesity ----- anovulatory cycles, the endometrium
is exposed to un-opposed oestrogen.
 In post-menopausal women:
obesity ----- increased conversion of
androstenedione to oestrone in adipose tissue +
lower levels of SHBG----- higher levels of
unopposed oestrogen.

22.  Increased levels of insulin and Insulin-like
growth factor-1 (IGF-1)
 Fat cells produce hormones, called
adipokines, that may stimulate or inhibit cell
growth. ( e.g. leptin, promote cell proliferation
, whereas adiponectin,, may have anti-
proliferative effects ).

23.  Fat cells may also have direct and indirect
effects on other tumor growth regulators,
including mammalian target of rapamycin
(mTOR) and AMP-activated protein kinase.
 Obese people often have chronic low-level, or
“sub-acute,” inflammation, which has been
associated with increased cancer risk.
 Other possible mechanisms include altered
immune responses, effects on the nuclear
factor kappa beta system, and oxidative
stress.

24.  Apple-shaped
people who put on
weight around their
stomach may have
higher risks than
pear-shaped
people who put on
weight around their
hips.

25.  Abdominal fat is measured using either waist
circumference or waist-to-hip ratio .
 Studies have found that people with larger
waists or waist-to-hip ratios have higher
risks of certain cancers .
 Normal waist-to-hip ratio in female 0.7,waist
is 30% smaller than hip.

26.  A study was conducted in Alexandria, Egypt.
◦ It intended to assess the relation between different
measures of obesity and the risk to develop
endometrial cancer in Egyptian females with
postmenopausal bleeding (PMB).
◦ Result: Using ROC curve analysis, only the measure
of abdominal obesity (waist circumference) showed
significant accuracy in predicting endometrial
cancer (area = 0.63, P < .05). The best cutoff point
that maximizes accuracy was 88 cm.
Zaki.A, Gaber.A, Ghanem .E, Moemen.M, Shehata G. Biomedical Informatics and Medical
Statistics Department, Medical Research Institute, Alexandria University, Egypt.

28.  Research is focusing on improved evaluation
of risk, so that women can receive the
optimal chemo-preventive agent when
diagnosed as being at high risk of cancer.
Risk Identification
Preventive measures
Screening
Program

29.  Obese women.
 Early Menarche.
 Late Menopause.
 Polycystic ovary syndrome.
 Type 2 Diabetes.
 Hypertension.
 An-ovulatory Infertility.
 HNPCC (hereditary non-polyposis colon cancer)
 Tamoxifin therapy.
 HRT.

30.  Weight loss: Life Style changes(diet & exercise).
Pharmaco-therapy .
Bariatric surgeries.
 Chemo-prophylaxis :*COCP
*Oral progesterone
*Injectable progesterone
* Mirena IUS

31.  Large studies are now trying to confirm that
losing weight may reduce cancer risk.
 One study : loss of 20 pounds ---11%
decrease in overall cancer risk.
 Another study: women who had sustained
some degree of weight loss for 5 years or
more had a 25% lower risk of developing
endometrial cancer than those who had not
lost weight.(1)
Trentham-Dietz A, Nichols H, Hampton J, Newcomb P. Weight change and risk
of endometrial cancer. Int J Epidemiol 2006

32. Weight
loss
Non-surgical
Behavioral changesDiet
Exercise Pharmacotherapy
Bariatric surgery

33.  Traditional methods
of weight loss are less
successful than
bariatric surgery to
induce successful
long-term weight
loss.!!!!!!!!

34.  A study based on ongoing Swedish Obese
Subjects trial :
Bariatric surgery that results in sustained
weight loss may help to reduce cancer risk in
obese women.
The Lancet Oncology, Swedish study based on ongoing Swedish Obese Subjects trial

35.  COC use for about 3 years reduces a
women's risk of developing endometrial
cancer by about 50%.
 Use of COCs for 10 years or more reduces a
woman's risk of developing such cancers by
80%.
 The protective effect lasts for up to 20 years
after cessation of COCs.
Hannaford PC, Selvaraj S, Elliott AM, Angus V, Iversen L, Lee AJ. “Cancer risk
among users of oral contraceptives: cohort data from the Royal College of
Practitioner’s oral contraception study”. BMJ online 12 Sept 2007

36.  However , Obese women using oral
contraceptives may also have a higher failure
rate as a contraceptive .
 Also obesity complications as hypertension ,
diabetes, cardiovascular disease and
thrombo-embolism may limit COCs use.

37.  Depo-Provera reduces the risk of endometrial
cancer by 80%.
 The reduced risk of endometrial cancer in Depo-
Provera users is thought to be due to both the
direct anti-proliferative effect of progestogen on
the endometrium and the indirect reduction of
estrogen levels by suppression of ovarian
follicular development.
WHO Collaborative Study of Neoplasia and Steroid Contraceptives (1991). "Depot-
medroxyprogesterone acetate (DMPA) and risk of endometrial cancer". Int J Cancer

38.  DMPA ( Depo-Provera) and the combination
contraceptive vaginal ring (NuvaRing) are
most effective for obese women because
they don't appear to be affected by body
weight.

39.  Progestogen-containing IUCDs (Mirena) might
considered partially chemo-preventive although
as yet there are no data to support them being
prophylactic.
 The POET study (Prevention Of Endometrial
Tumours), shortly to be launched, will look at a
small group of women who are deemed to be
genetically predisposed to develop endometrial
cancer at a young age and will evaluate
progestogen-containing IUCDs in this setting.

40. Year Total
cc.
Pill Injecta
ble
+Impla
nts
IUCD Female
Sterliz
Male
Sterliz
Condo
m
UK 2002 84 % 22 % 3 % 6 % 13% 17% 18%
Egypt 2003 60% 9.3 % 8.8% 36.7% 0.9% 0% 0.9%
United Nations .Department of economic & social affairs. Population
Division. World contraceptive use.

42.  At present, there are not screening methods with
acceptable sensitivity and specificity.
 Ultrasound imaging: endometrial thickness 4 mm
cut value reliable in postmenopausal women
experiencing bleeding, but the test carries a high
false positive rate in asymptomatic women.
 The idea that combination of TVS and color
Doppler can reduce the number of false-positive
findings, are still under research .
Gupta, J.K., et al., Ultrasonographic endometrial thickness for diagnosing
endometrial pathology in women with postmenopausal bleeding: a meta-
analysis. Acta Obstet Gynecol Scand, 2002

43.  Cytological sampling is technically viable, but
there is no evidence from RCTs to support its
use .
 The Cancer Genetics Studies Consortium
recommends gynaecological screening for
women with HNPCC syndrome, but there is
no clear evidence that ultrasound screening
in this group is of benefit.

45.  Standard treatment ( Abdominal hysterectomy
and bilateral SO , with or without radiotherapy
and/or chemotherapy).
 Laparoscopic hysterectomy.
 Primary Radiotherapy.

46.  Hysterectomy and bilateral SO , with or without
radiotherapy and/or chemotherapy as indicated.
 Obesity is associated with an increase risk of
peri-operative complications due to associated
disorders as diabetes, hypertension, and
cardiovascular disease.
 In morbidly obese women , obstructive sleep
apnoea is 10 times more common and puts post-
operative patients at risk of arrhythmia and
acute cardiac events.
 So, more detailed preoperative assessment to
exclude co-existing morbidity and more
intensive postoperative care is required.

47.  Neither the PORTEC trial nor the more recent
ASTEC trial has suggested a meaningful role
for pelvic lymph-adenectomy, although
sampling of the nodes remains a part of FIGO
staging.

48.  Laparoscopic hysterectomy &bilateral SO has
been demonstrated to be the surgical
technique of choice for women with
endometrial cancer in three large RCTs :
1. The American RCT, the Gynecologic Oncology Group
(GOG) LAP2 study.
2. The Australian, New Zealand and Hong Kong RCT.
3. The Dutch RCT.
However, a higher conversion rate to open surgery
was noticed with high BMI.

49.  Endometrial cancer is radiosensitive.
 Radiotherapy may be used as a sole
treatment modality.
 There have been no direct comparisons of
primary radiotherapy with surgery in women
with local disease and significant co-
morbidities, early case series suggest that
primary radiotherapy has inferior survival
rates compared to hysterectomy.
Inciura, A., et al., Long-term results of high-dose-rate brachytherapy and
external-beam radiotherapy in the primary treatment of endometrial cancer.
J Radiat Res (Tokyo)

50.  May be used in selected cases for fertility
reservation.
 Early case series to be used in early stages
with obesity co-morbidites.
 In atypia & well-differentiated stage (1a )
cancer.

51.  Obesity is now clearly established as a major risk
factor for endometrial cancer.
 In medium income country like ours , Obesity
prevention and lifestyle initiatives should
become the responsibility of public health
services. Stepwise programmes with realistic
time-related goals are required, starting with
modification of lifestyle, progressing to
pharmacotherapy and ultimately obesity surgery.
 The real challenge now is to triage those women
at a higher risk and offer them prophylactic
measures as COCPs ,DMPA, oral progesterone or
Mirena coil.

52.  Standard treatment for endometrial cancer is
surgery.
 Obesity is associated with numerous disorders
which put the patient at increase risk of peri-
operative complications that require more
detailed pre-operative assessment and more
intensive post-operative care.
 Thus treatment for endometrial cancer needs to
be reassessed in the complex and increasingly
common situation of the obese, older women
with this disease.

53.  THANK YOU