Endometrial Cancer

Faina Linkov, PhDResearch Assistant Professor

University of Pittsburgh Cancer Institute

GENERAL OVERVIEW OF GYNECOLOGIC CANCERS

• 79,480 new cases/yr of female genital system cancers in the U.S.

• 28,910 deaths in U.S. from genital system cancers in 2005

• Diet, exercise and lifestyle choices play important roles in the prevention of cancer

• Knowledge of family history also increases prevention and early diagnosis rates

• Regular screening and self-examinations for appropriate cancers early detection early intervention & therapy

Endometrial Cancer

• Strong association with excess weight

Adipose tissue: Consequences of Obesity on Cancer Development

Obesity has been implicated in the development of • Type 2 diabetes• Heart disease• Stroke• Hypertension• Gallbladder disease• Osteoarthritis• Sleep apnea• Asthma• Psychological disorders or difficulties

• Some cancers, including ovarian, cervical, breast, and endometrial

• Dyslipidemia• Complications of pregnancy• Hirsuitism• Menstrual abnormalities• Stress incontinence• Increased surgical risk

Endometrial Cancer and Lifestyle

Important DefinitionsImportant Definitions

• Obesity: having a very high amount of body fat in relation to lean body mass, or Body Mass Index (BMI) of 30 or higher for adults.

• Body Mass Index (BMI): a measure of weight in relation to height, specifically weight in kilograms divided by the square of his or her height in meters.

• Morbid Obesity-100 pounds above ideal weight or BMI over 40 (indication for bariatric surgery)

• Bariatric surgery is the term for operations to help promote weight loss.

• Obesity: having a very high amount of body fat in relation to lean body mass, or Body Mass Index (BMI) of 30 or higher for adults.

• Body Mass Index (BMI): a measure of weight in relation to height, specifically weight in kilograms divided by the square of his or her height in meters.

• Morbid Obesity-100 pounds above ideal weight or BMI over 40 (indication for bariatric surgery)

• Bariatric surgery is the term for operations to help promote weight loss.

Obesity Trends* Among U.S. AdultsBRFSS, 2005

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

ENDOMETRIAL CANCER

• Cancer of the uterine endometrial lining• Most common female reproductive

cancer– 40,000 new cases/year– 7,000 deaths/year

• Most of these malignancies are adenocarcinoma

Incidence and Prevalence

• Most common gynecologic cancer

• 4th most common in women (US)

• 2nd most common in women (UK)

• 5th most common in women (worldwide)

• Western developed > Southeast Asia

• Increase in the 1970’s– Increased use of menopausal estrogen therapy

RISK FACTORS FOR ENDOMETRIAL CANCER

• Early menarche (<age 12)• Late menopause

(>age 52)

• Infertility or nulliparous• Obesity• Treatment with tamoxifen

for breast cancer• Estrogen replacement

therapy (ERT) after menopause

• Diet high in animal fat

• Diabetes• Age greater than 40• Caucasian women• Family history of

endometrial cancer or hereditary nonpolyposis colon cancer (HNPCC)

• Personal history of breast or ovarian cancer

• Prior radiation therapy for pelvic cancer

Endometrial Carcinoma

Etiology• Unnoposed estrogen

hypothesis: exposure to unopposed estrogens

Pathology• Spreads through uterus,

fallopian tubes, ovaries and out into peritoneal cavity– Metastasizes via blood and

lymphatic system

SYMPTOMS OFENDOMETRIAL CANCER

• Symptoms– Non-menstrual bleeding or discharge

• Especially post-menopausal bleeding

– Heavy bleeding– Dysuria– Pain during intercourse– Pain and/or mass in pelvic area– Weight loss– Back pain

ENDOMETRIAL CANCER

• Diagnosis– Pelvic examination– Pap smear (detect cancer

spread to cervix)– Endometrial biopsy– Dilation and curettage– Transvaginal ultrasound

• Treatment– Surgery

• Hysterectomy• Salpingo-oophorectomy• Pelvic lymph node

dissection• Laparoscopic lymph node

sampling

– Radiation therapy– Chemotherapy– Hormone therapy

• Progesterone• Tamoxifen

Endometrial hyperplasia

• Overgrowth of the glandular epithelium of the endometrial lining

• Usually occurs when a patient is exposed to unopposed estrogen, either estrogenically or because of anovulation

• Rates of neoplasm– simple hyperplasia: 1%. – complex hyperplasia with atypia: 30%

Endometrial Hyperplasia

• Complex hyperplasia with atypia– One study found incidence of concomitant

endometrial cancer in 40% of cases– Hysterectomy or high dose progestin tx

• Simple– Often regress spontaneously– Progestin treatment used for treating bleeding

may help in treating hyperplasia as well

• Estrogen dependent disease– Prolonged exposure without the balancing effects

of progesterone

• Premalignant potential– Endometrial hyperplasia– Simple => 1%– Complex => 3%– Simple with atypia => 8%– Complex with atypia => 29%

Reduced Risk• Oral Contraceptives

– Combined OC => 50% reduced rate

– Actual reduction number small because uncommon in women of child bearing age

– Long term offers protection

– Reduced risk presumably => progesterone

• Tobacco Smoking– Some evidence that it reduces the rate

– Smokers have lower levels of estrogen and lower rate of obesity

Prevention and Survival

• Early detection is best prevention• Treating precancerous hyperplasia

– Hormones (progestin)– D&C– Hysterectomy– 10 ~ 30% untreated develop into cancer

• Average 5 year survival– Stage I => 72 ~ 90%– Stage II=> 56 ~ 60%– Stage III => 32 ~ 40%– Stage IV => 5 ~ 11%

Potentially modifiable risk factors

Dietary factorsIsoflavones:

Phytoestrogens that have properties similar to selective estrogen receptor modulators

Soy, beans, chick peas…

Dietary fiber

Increases estrogen excretion and decreases estrogen reuptake: whole grains, vegetables, fruits, and seaweeds

Exercise?

Summary points

• Endometrial cancer is one of the leading gynecological cancers in the US

• Obesity is one of the key factors involved in Endometrial cancer development

• More research is needed to explore modifiable risk factors in endometrial cancer development