Endometrial Cancer

Endometrial CancerEndometrial Cancer

Nancy Wozniak, MDNancy Wozniak, MD

Endometrial CancerEndometrial Cancer

The most common gyne malignancy The most common gyne malignancy in the U.S.in the U.S.

6% of all cancers in women6% of all cancers in women

Generally high rate of survival due Generally high rate of survival due to early diagnosisto early diagnosis

Risk factors…Risk factors…

Epidemiologic diffences:Epidemiologic diffences:Risk related to hormonal stimulationRisk related to hormonal stimulationor unrelated to estrogen at all.or unrelated to estrogen at all.

Estrogen-related endometrial cancer (Type Estrogen-related endometrial cancer (Type I) tends to I) tends to be a lower grade histologically.be a lower grade histologically.

Endometrial cancers unrelated to Endometrial cancers unrelated to hormones (Type II)hormones (Type II)

tend to be a higher grade and stage eg. tend to be a higher grade and stage eg. Papillary serous or Papillary serous or clear cell tumors.clear cell tumors.

How endometrial hyperplasia is How endometrial hyperplasia is associated with endometrial cancerassociated with endometrial cancer

Endometrial hyperplasia is a Endometrial hyperplasia is a continuum…continuum…

Simple hyperplasiaSimple hyperplasiacomplex complex hyperplasia without atypiahyperplasia without atypiacomplex complex hyperplasia w/ atypiahyperplasia w/ atypia endometrial endometrial cancer (well differentiated cancer (well differentiated adenocarcinoma)adenocarcinoma)

How endometrial hyperplasia is How endometrial hyperplasia is associated with endometrial cancerassociated with endometrial cancer

Simple hyperplasia– 1% progress to Simple hyperplasia– 1% progress to endometrial cancerendometrial cancer

Complex hyperplasia– 3%Complex hyperplasia– 3%

Complex hyperplasia with atypia—28%Complex hyperplasia with atypia—28%

30-40% of endometrial cancers are found 30-40% of endometrial cancers are found in a background of atypical hyperplasia. in a background of atypical hyperplasia. Overall, these tend to be lower grade Overall, these tend to be lower grade tumors.tumors.

Risk factors for endometrial Risk factors for endometrial cancercancer

These risk factors are only helpful in These risk factors are only helpful in identifying women at risk for type I identifying women at risk for type I disease.disease.

For type I disease, what would be For type I disease, what would be some common exogenous estrogen some common exogenous estrogen

sources?sources?

Unopposed estrogen in HRTUnopposed estrogen in HRT

TamoxifenTamoxifen

What would be endogenous sources of What would be endogenous sources of estrogen as a risk factor for estrogen as a risk factor for

endometrial cancer?endometrial cancer?Obesity– adrenal precursors gets Obesity– adrenal precursors gets

converted to estrogens in the adipose converted to estrogens in the adipose cells. (Estrone hypothesis) These cells. (Estrone hypothesis) These women often have lower SHBG, too.women often have lower SHBG, too.

Anovulatory cyclesAnovulatory cycles

Estrogen secreting tumorsEstrogen secreting tumors

Endometrial cancer NOT assoc. w/ Endometrial cancer NOT assoc. w/ estrogenestrogen(Type II)(Type II)Papillary serousPapillary serous

Clear cell tumorsClear cell tumors

Usually these affect multiparous, but Usually these affect multiparous, but generally healthy, older patients.generally healthy, older patients.

For type I disease, what would be For type I disease, what would be some common exogenous estrogen some common exogenous estrogen

sources?sources?

Unopposed estrogen in HRTUnopposed estrogen in HRT

TamoxifenTamoxifen

The Benefits and Risks of The Benefits and Risks of Estrogen in HRTEstrogen in HRT

Benefits: helps relieve hot flashes, vaginal dryness, Benefits: helps relieve hot flashes, vaginal dryness, and preventing osteoporosis.and preventing osteoporosis.

Unopposed estrogen increases the risk of Unopposed estrogen increases the risk of endometrial hyperplasia and endometrial cancer.endometrial hyperplasia and endometrial cancer.

With unopposed estrogen 20-50% of women will With unopposed estrogen 20-50% of women will have developed endometrial hyperplasia after 1 have developed endometrial hyperplasia after 1 year. Risk of endometrial cancer is related BOTH year. Risk of endometrial cancer is related BOTH to dose and duration of treatment. Thus, in to dose and duration of treatment. Thus, in women taking estrogen alone for 10 years, the women taking estrogen alone for 10 years, the incidence of endometrial cancer goes from 1/1000 incidence of endometrial cancer goes from 1/1000 to 42/1000. to 42/1000. May May be a less aggressive cancer… be a less aggressive cancer…

TamoxifenTamoxifen

Tamoxifen– a competitive inhibitor of Tamoxifen– a competitive inhibitor of estrogen binding to estrogen receptors estrogen binding to estrogen receptors that also has partial agonist activity that also has partial agonist activity (tamoxifen is a weak estrogen)(tamoxifen is a weak estrogen)

- used in pts. w/ early stage breast - used in pts. w/ early stage breast caca

- as treatment of recurrent disease- as treatment of recurrent disease

- risk reduction in high risk women- risk reduction in high risk women

TamoxifenTamoxifen

Unfortunately while it suppresses Unfortunately while it suppresses breast tissue growth, it stimulates breast tissue growth, it stimulates endometrial lining. endometrial lining.

Probably a 2 to 3 fold risk of Probably a 2 to 3 fold risk of endometrial cancer w/tamoxifen. endometrial cancer w/tamoxifen.

EspeciallyEspecially in women older than 50 in women older than 50

TamoxifenTamoxifen

What’s ACOG have to say about tamoxifen?...What’s ACOG have to say about tamoxifen?... Even though tamoxifen is associated with Even though tamoxifen is associated with

endometrial cancer, the benefits in treating endometrial cancer, the benefits in treating women with breast ca. outweigh the risks…women with breast ca. outweigh the risks…but…but…-women need a yearly gyne exam-women need a yearly gyne exam-women should monitor themselves for abnormal -women should monitor themselves for abnormal

vaginal sx., e.g . Bleeding, discharge, etcvaginal sx., e.g . Bleeding, discharge, etc-screening such as pelvic U.S. is NOT -screening such as pelvic U.S. is NOT recommended (too many false positives)recommended (too many false positives)-Limit tamoxifen use to 5 years-Limit tamoxifen use to 5 years-if there is atypical endometrial hyperplasia, treat -if there is atypical endometrial hyperplasia, treat and reassess tamoxifen (ie. Consider hysterectomy)and reassess tamoxifen (ie. Consider hysterectomy)

Other risk factors for endometrial Other risk factors for endometrial cancercancer

Obesity- Obesity-

increased risk associated with obesity increased risk associated with obesity but it is NOT related to the but it is NOT related to the distribution of adipose tissue… distribution of adipose tissue…

obese women have high levels of obese women have high levels of endogenous estrogen probably from the endogenous estrogen probably from the conversion of androstenedione to estrone and the conversion of androstenedione to estrone and the aromatization of androgens to estrogen both of aromatization of androgens to estrogen both of which occur in the adipose tissuewhich occur in the adipose tissue


Diabetes and HTNDiabetes and HTN

a risk factor because these a risk factor because these conditions are often associated with conditions are often associated with obesity, and also because of the obesity, and also because of the effects of hyperinsulinemia and effects of hyperinsulinemia and insulin-like growth factors.insulin-like growth factors.


Chronic anovulation—Chronic anovulation—

Many women with chronic anovulation have Many women with chronic anovulation have plenty of estrogen since androgens can be plenty of estrogen since androgens can be converted peripherally to estrogen, but converted peripherally to estrogen, but anovulatory cycles lack progesterone (luteal anovulatory cycles lack progesterone (luteal phase). Thus even though these women have phase). Thus even though these women have hyperandrogenism, they also have chronic hyperandrogenism, they also have chronic estrogen stimulation and can develop estrogen stimulation and can develop endometrial hyperplasia even at a young age.endometrial hyperplasia even at a young age.


Familial predispositionFamilial predisposition

Eg Lynch syndrome II : hereditary Eg Lynch syndrome II : hereditary nonpolyposis colorectal cancer (HNPCC), nonpolyposis colorectal cancer (HNPCC), endometrial carcinoma.endometrial carcinoma.

(up to 43% of women of affected families will (up to 43% of women of affected families will develop ovarian cancer)develop ovarian cancer)

Unclear if there’s a risk with BRCA 1 and 2Unclear if there’s a risk with BRCA 1 and 2


ParityParity

Nulliparity in and of itself is not a risk Nulliparity in and of itself is not a risk factor as much as the anovulatory factor as much as the anovulatory cycles that are associated with cycles that are associated with infertility/infertility/


Diet– especially high fatDiet– especially high fat

Menarche/Menopause: early Menarche/Menopause: early menarche and late menopausemenarche and late menopause

essentially prolonged estrogen essentially prolonged estrogen exposure exposure without the protection without the protection of progesterone.of progesterone.

Protective FactorsProtective Factors

Oral contraceptives:Oral contraceptives:

decreases both the risk of ovarian decreases both the risk of ovarian and and endometrial cancer (RR = 0.6 if endometrial cancer (RR = 0.6 if used for one used for one year…effect lasts for 15 year…effect lasts for 15 years!)years!)

Protective effect probably due to Protective effect probably due to progesterone.progesterone.

Protective FactorsProtective Factors

Physical activityPhysical activity

Smoking Smoking

HistopathologyHistopathology

Most common types of endometrial cancer:Most common types of endometrial cancer:

Endometriod adenocarcinoma (70-80%)Endometriod adenocarcinoma (70-80%)

Clear cell and serous tumors are more Clear cell and serous tumors are more aggressive and probably present at a aggressive and probably present at a more advanced age. (together 5-10%)more advanced age. (together 5-10%)

Mucinous and squamous about 2%Mucinous and squamous about 2%

Clinical presentationClinical presentation

The “classic symptom” is abnormal The “classic symptom” is abnormal uterine bleedinguterine bleeding

20-30% of women with post-20-30% of women with post-menopausal bleeding will have uterine menopausal bleeding will have uterine cancer. cancer.

( the risk is higher the farther they ( the risk is higher the farther they are away from menopause)are away from menopause)

Clinical presentationClinical presentation

Abnormal pap smearAbnormal pap smearnot a reliable means of picking up not a reliable means of picking up endometrial ca.endometrial ca.

The presence of endometrial cells on a pap The presence of endometrial cells on a pap smear in women > 40 is an indication for bx. smear in women > 40 is an indication for bx. Even more likely if cells are atypical…if Even more likely if cells are atypical…if cancer present, it is often of higher grade, cancer present, it is often of higher grade, with deeper invasion, more advanced stage.with deeper invasion, more advanced stage.

Hyperplasia in 36%Hyperplasia in 36%Adenoca in 11%Adenoca in 11%

DiagnosisDiagnosis

Easy to do with office EMBEasy to do with office EMBHysteroscopy w/ D & C (gold standard)Hysteroscopy w/ D & C (gold standard)

Detection rates of endometrial ca. by Detection rates of endometrial ca. by pipelle was between 91 and 99%pipelle was between 91 and 99%Detection of hyperplasia was 81%Detection of hyperplasia was 81%

Recommendation: EMB as initial test; Recommendation: EMB as initial test; Hysteroscopy/D&C if EMB inconclusive or Hysteroscopy/D&C if EMB inconclusive or high suspicion (hyperplasia with atypia, high suspicion (hyperplasia with atypia, pyometria, presence of necrosis, or pyometria, presence of necrosis, or persistant bleeding)persistant bleeding)

Transvaginal ultrasoundTransvaginal ultrasound

In postmenopausal women, an endometrial In postmenopausal women, an endometrial thickness of 4-5 mm or less is pretty reassuring.thickness of 4-5 mm or less is pretty reassuring.(only 1% will have endometrial ca. if nl (only 1% will have endometrial ca. if nl endometrial thickness) ?? If nl TVS do you need endometrial thickness) ?? If nl TVS do you need an EMB w/abnl bleeding.an EMB w/abnl bleeding.

A thicker endometrium requires EMB, A thicker endometrium requires EMB, hysteroscopy/D&Chysteroscopy/D&C

Especially useful for women on estrogen who have Especially useful for women on estrogen who have bleeding who have bleeding, but overall TVS is bleeding who have bleeding, but overall TVS is not recommended as a screening tool.not recommended as a screening tool.

Transvaginal ultrasoundTransvaginal ultrasound

It is still recommended to do an EMB It is still recommended to do an EMB rather than rely on TVS results in rather than rely on TVS results in evaluating abnormal bleedingevaluating abnormal bleeding

Cancer StagingCancer Staging

Staging is always done surgicallyStaging is always done surgically

Requires a total hysterectomy, BSORequires a total hysterectomy, BSO

Uterine specimen should be Uterine specimen should be opened in the opened in the room to evaluate room to evaluate extent of disease.extent of disease.

Can omit LN sampling if risk of Can omit LN sampling if risk of lymphnode lymphnode spread is low.spread is low.


Patterns of metastatic spread:Patterns of metastatic spread:

Pelvic and paraaortic lymph nodes, Pelvic and paraaortic lymph nodes, lung, inguinal and supraclavicular lung, inguinal and supraclavicular nodes, liver, peritoneal cavity, bone, nodes, liver, peritoneal cavity, bone, brain, and vaginabrain, and vagina


Pre-op imagingPre-op imaging

CXRCXR

CT (not necessary unless you think CT (not necessary unless you think there’s there’s extra pelvic disease– it extra pelvic disease– it doesn’t alter tx doesn’t alter tx and doesn’t and doesn’t really let you know of really let you know of depth of invasion etc.– MRI would be depth of invasion etc.– MRI would be

better in assessing invasion)better in assessing invasion)


LabsLabs

CA-125CA-125

LFT’s LFT’s

CBCCBC

RenalRenal

HNPCC and ScreeningHNPCC and Screening

Since 40-60% of patients with this develop Since 40-60% of patients with this develop endometrial ca., do an EMB at age 35endometrial ca., do an EMB at age 35

-women with HNPCC-associated -women with HNPCC-associated mutationsmutations

-women with a family member with -women with a family member with this this mutationmutation

-women from families with autosomal -women from families with autosomal dominant predisposition to colon ca.dominant predisposition to colon ca.

Doing an ultra sound is not enough!Doing an ultra sound is not enough!

Documents

Endometrial Cancer