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Endometrial Cancer Faina Linkov, PhD 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 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. Adults BRFSS, 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 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