Endometrial Cancer Faina Linkov Ph D Research Assistant

Endometrial Cancer Faina Linkov, Ph. D Research 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 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 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. Adults BRFSS, 2005 (*BMI ≥ 30, or ~ 30 lbs overweight for 5’ 4” person) No Data ≥ 30% <10% 10%– 14% 15%– 19% 20%– 24% 25%– 29%

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 4 th most common in women (US) 2 nd most common in women (UK) 5 th 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 OF ENDOMETRIAL 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 factors Isoflavones: 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