Endometrial Cancer Faina Linkov, PhDResearch Assistant ProfessorUniversity of Pittsburgh Cancer Institute

*Faina Linkov, PhDResearch Assistant Professor of Medicine and EpidemiologyUniversity of Pittsburgh Cancer InstituteE-mail (preferred mode of communications): fyL1 (at) pitt.edu

GENERAL OVERVIEW OF GYNECOLOGIC CANCERS79,480 new cases/yr of female genital system cancers in the U.S. 28,910 deaths in U.S. from genital system cancers in 2005Diet, exercise and lifestyle choices play important roles in the prevention of cancerKnowledge of family history also increases prevention and early diagnosis ratesRegular screening and self-examinations for appropriate cancers early detection early intervention & therapy

Endometrial CancerStrong association with excess weight

Adipose tissue: Consequences of Obesity on Cancer DevelopmentObesity has been implicated in the development of Type 2 diabetesHeart diseaseStrokeHypertensionGallbladder diseaseOsteoarthritisSleep apneaAsthmaPsychological disorders or difficultiesSome cancers, including ovarian, cervical, breast, and endometrialDyslipidemiaComplications of pregnancyHirsuitismMenstrual abnormalitiesStress incontinenceIncreased surgical risk

Endometrial Cancer and Lifestyle

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Important DefinitionsObesity: 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

ENDOMETRIAL CANCERCancer of the uterine endometrial liningMost common female reproductive cancer40,000 new cases/year7,000 deaths/yearMost of these malignancies are adenocarcinoma

*These are the statistics for the US population

Incidence and PrevalenceMost common gynecologic cancer4th most common in women (US)2nd most common in women (UK)5th most common in women (worldwide)Western developed > Southeast AsiaIncrease in the 1970sIncreased use of menopausal estrogen therapy

RISK FACTORS FOR ENDOMETRIAL CANCEREarly menarche

(age 52)Infertility or nulliparousObesityTreatment with tamoxifen for breast cancerEstrogen replacement therapy (ERT) after menopauseDiet high in animal fat

DiabetesAge greater than 40Caucasian womenFamily history of endometrial cancer or hereditary nonpolyposis colon cancer (HNPCC)Personal history of breast or ovarian cancerPrior radiation therapy for pelvic cancer

Endometrial CarcinomaEtiologyUnnoposed estrogen hypothesis: exposure to unopposed estrogens

PathologySpreads through uterus, fallopian tubes, ovaries and out into peritoneal cavityMetastasizes via blood and lymphatic system

*Unopposed estrogen hypothesis is the theoretical framework used to explain the relationship between endogenous steroid hormones and endometrial cancer risk. This hypothesis proposes that that endometrial cancer may develop as a result of the mitogenic effects of estrogens, when these are insufficiently counterbalanced by progesterone. In etiological terms, any factor that increases exposure to unopposed estrogens (such as estrogen therapy obesity, and irregular menstrual cycles) tends to increase the risk of the disease, while factors that decrease exposure to estrogens or increase progesterone levels (such as oral contraceptives or smoking) tend to be protective.

SYMPTOMS OFENDOMETRIAL CANCERSymptomsNon-menstrual bleeding or discharge Especially post-menopausal bleedingHeavy bleedingDysuriaPain during intercoursePain and/or mass in pelvic areaWeight lossBack pain

ENDOMETRIAL CANCERDiagnosisPelvic examinationPap smear (detect cancer spread to cervix)Endometrial biopsyDilation and curettageTransvaginal ultrasound

TreatmentSurgeryHysterectomySalpingo-oophorectomyPelvic lymph node dissectionLaparoscopic lymph node samplingRadiation therapyChemotherapyHormone therapyProgesteroneTamoxifen

Endometrial hyperplasia Overgrowth of the glandular epithelium of the endometrial liningUsually occurs when a patient is exposed to unopposed estrogen, either estrogenically or because of anovulationRates of neoplasmsimple hyperplasia: 1%. complex hyperplasia with atypia: 30%

Endometrial HyperplasiaComplex hyperplasia with atypiaOne study found incidence of concomitant endometrial cancer in 40% of casesHysterectomy or high dose progestin txSimpleOften regress spontaneouslyProgestin treatment used for treating bleeding may help in treating hyperplasia as well

Estrogen dependent diseaseProlonged exposure without the balancing effects of progesteronePremalignant potentialEndometrial hyperplasiaSimple => 1%Complex => 3%Simple with atypia => 8%Complex with atypia => 29%

Reduced RiskOral ContraceptivesCombined OC => 50% reduced rateActual reduction number small because uncommon in women of child bearing ageLong term offers protection Reduced risk presumably => progesteroneTobacco SmokingSome evidence that it reduces the rateSmokers have lower levels of estrogen and lower rate of obesity

Prevention and SurvivalEarly detection is best preventionTreating precancerous hyperplasiaHormones (progestin)D&CHysterectomy10 ~ 30% untreated develop into cancerAverage 5 year survivalStage 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 fiberIncreases estrogen excretion and decreases estrogen reuptake: whole grains, vegetables, fruits, and seaweeds

Exercise?

Summary pointsEndometrial cancer is one of the leading gynecological cancers in the US Obesity is one of the key factors involved in Endometrial cancer developmentMore research is needed to explore modifiable risk factors in endometrial cancer development

*Faina Linkov, PhDResearch Assistant Professor of Medicine and EpidemiologyUniversity of Pittsburgh Cancer InstituteE-mail (preferred mode of communications): fyL1 (at) pitt.edu*

*We have never had an epidemic like this that we have been able to track so thoroughly and see. As I told you, this is conservative.About 60 million adults, or 30 percent of the adult population, are now obese, which represents a doubling of the rate since 1980.

*These are the statistics for the US population*Unopposed estrogen hypothesis is the theoretical framework used to explain the relationship between endogenous steroid hormones and endometrial cancer risk. This hypothesis proposes that that endometrial cancer may develop as a result of the mitogenic effects of estrogens, when these are insufficiently counterbalanced by progesterone. In etiological terms, any factor that increases exposure to unopposed estrogens (such as estrogen therapy obesity, and irregular menstrual cycles) tends to increase the risk of the disease, while factors that decrease exposure to estrogens or increase progesterone levels (such as oral contraceptives or smoking) tend to be protective.