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UTERINE CANCER
● University of Traditional Medicine
Prepared by Ali Al-Hayali
To Doctor Arsen Minasyan
GM-603 Group roup
ONCOLOGY
The uterus is a hollow organ, normally about the size and shape
of a medium-sized pear. The uterus is where a fetus grows and
develops when a woman is pregnant. It has 2 main parts (see
image below):
• The upper part of the uterus is called the body or the corpus.
• The cervix is the lower end of the uterus that joins it to the
vagina.
The body of the uterus has 2 main layers:
• The myometrium is the outer layer. This thick layer of muscle
is needed to push the baby out during birth.
• The endometrium is the inner layer.
During a woman's menstrual cycle, hormones cause the endometrium to change. Estrogen causes the endometrium
to thicken so that it could nourish an embryo if pregnancy occurs. If there is no pregnancy, estrogen is produced in
lower amounts and more of the hormone called progesterone is made. This causes the endometrial lining to shed
from the uterus and become the menstrual flow (period). This cycle repeats until menopause.
INTRODUCTION
1. Incidence: Uterine cancer is the fourth most common cancer and the sixth most
common cause of death among women in the United States. It is the most frequent
gynecologic cancer in the United States, with an estimated 66,200 new cases and
13,030 deaths in 2023
2. Age: Uterine cancer primarily affects postmenopausal women, with the highest
incidence occurring between the ages of 50 and 70. However, it can also occur in
younger women, especially those with certain risk factors.
3. Risk factors: Several factors increase the risk of developing uterine cancer,
including obesity, hormonal imbalances (such as estrogen dominance), diabetes,
hypertension, certain genetic conditions (such as Lynch syndrome), and a history of
endometrial hyperplasia or polycystic ovary syndrome (PCOS).
4. Geographical variation: The incidence of uterine cancer varies across different
regions and countries. It is more common in developed countries with higher rates of
obesity and sedentary lifestyles.
5. Racial and ethnic disparities: Uterine cancer rates differ among racial and ethnic
groups. In the United States, for example, African American women have higher
incidence and mortality rates compared to other racial groups.
6. Survival rates: The prognosis for uterine cancer is generally favorable, especially
when diagnosed at an early stage. The five-year survival rate for localized uterine
cancer is around 95%. However, the prognosis worsens with advanced stages of the
disease.
EPIDEMIOLOGY OF UTERINE CANCER
• Ovarian tumors: A certain type of ovarian tumor, the granulosa cell tumor, often makes estrogen. Estrogen made by one of these tumors
isn't controlled the way hormone release from the ovaries is, and it can sometimes lead to high estrogen levels. The resulting hormone
imbalance can stimulate the endometrium and even lead to endometrial cancer.
• Polycystic ovarian syndrome: Women with a condition called polycystic ovarian syndrome (PCOS) have abnormal hormone levels, such as
higher androgen (male hormones) and estrogen levels and lower levels of progesterone. The increase in estrogen relative to progesterone can
increase a woman's chance of getting endometrial cancer. PCOS is also a leading cause of infertility in women.
• Diet and exercise: A high-fat diet can increase the risk of many cancers, including endometrial cancer. Because fatty foods are also high-
calorie foods, a high-fat diet can lead to obesity, which is a well-known endometrial cancer risk factor. Many scientists think this is the main
way in which a high-fat diet raises endometrial cancer risk. Some scientists think that fatty foods may also have a direct effect on how the
body uses estrogen, which increases endometrial cancer risk. Physical activity lowers the risk of endometrial cancer. Many studies have
found that women who exercise more have a lower risk of endometrial cancer, while others
• Diabetes: Endometrial cancer may be about twice as common in women with type 2 diabetes. But diabetes is more common in people who
are overweight and less active, which are also risk factors for endometrial cancer. This makes it hard to find a clear link.
• Family history: Endometrial cancer tends to run in some families. Some of these families also have a higher risk for colon cancer. This
disorder is called hereditary nonpolyposis colon cancer (HNPCC). Another name for HNPCC is Lynch syndrome. In most cases, this disorder
is caused by a defect in either the mismatch repair gene MLH1 or the geneMSH2. But at least 5 other genes can cause HNPCC: MLH3,
MSH6, TGBR2, PMS1,and PMS2. An abnormal copy of any one of these genes reduces the body's ability to repair damage to its DNA or
control cell growth.
• Endometrial hyperplasia: Endometrial hyperplasia is an increased growth of the endometrium. Mild or simple hyperplasia, the most
common type, has a very small risk of becoming cancer. If the hyperplasia is called “atypical,” it has a higher chance of becoming a cancer.
• Prior pelvic radiation therapy: Radiation used to treat some other cancers can damage the DNA of cells, sometimes increasing the risk of a
second type of cancer9 such as endometrial cancer.
RISK FACTOR OF UTERINE CANCER
Although certain factors can increase a woman's risk for endometrial cancer, they don't always cause the disease. Many women with risk factors
never develop endometrial cancer.
• Obesity: Obesity is a strong risk factor for endometrial cancer and linked to hormone changes, which are covered in more detail below.A
woman's ovaries produce most of her estrogen before menopause. But fat tissue can change some other hormones (called androgens) into
estrogens. This can impact estrogen levels, especially after menopause. Having more fat tissue can increase a woman's estrogen levels, which
increases her endometrial cancer risk.
• Hormone factors: A woman's hormone balance plays a part in the development of most endometrial cancers. Many of the risk factors for
endometrial cancer affect estrogen levels. Before menopause, the ovaries are the major source of the 2 main types of female hormones are
estrogen and progesterone. The balance between these hormones changes each month during a woman's menstrual cycle. This produces a
woman's monthly periods and keeps the endometrium healthy. A shift in the balance of these hormones toward more estrogen increases a
woman's risk for endometrial cancer. After menopause, the ovaries stop making these hormones, but a small amount of estrogen is still made
naturally in fat tissue. Estrogen from fat tissue has a bigger impact after menopause than it does before menopause.
• Estrogen therapy: Estrogen treatment can help reduce hot flashes, improve vaginal dryness, and help prevent the weakening of the bones
(osteoporosis) that can occur with menopause. But using estrogen alone (without progesterone) can lead to endometrial cancer in women who
still have a uterus.
• Total number of menstrual cycles: Having more menstrual cycles during a woman's lifetime raises her risk of endometrial
cancer. Starting menstrual periods (menarche) before age 12 and/or going through menopause later in life raises the risk.
Pregnancy: The hormonal balance shifts toward more progesterone during pregnancy. So having many pregnancies helps protect against
endometrial cancer. Women who have never been pregnant have a higher risk, especially if they were also infertile (unable to become pregnant).
Tamoxifen: Tamoxifen is a drug that is used to help prevent and treatbreast cancer. Tamoxifen acts as an anti-estrogen in breast tissue, but it acts
like an estrogen in the uterus. In women who have gone through menopause, it can cause the uterine lining to grow,
which increases the risk of endometrial cancer.
The risk of developing endometrial cancer from tamoxifen is low (less than 1% per year).
RISK FACTOR OF UTERINE CANCER
CLASSIFICATION OF UTERINE CANCER
Uterine cancer can be classified into different types based on the specific cells involved
and their characteristics. The two main types of uterine cancer are:
1. Endometrial carcinoma: This is the most common type of uterine cancer,
accounting for about 80-90% of cases. It originates in the cells lining the uterus, known
as the endometrium. Occurs principally in post-menopausal women, and the incidence
rises with age. Also Commoner in obese women, in whom oestrogen is peripherally
produced in fat. Classified into two subtypes:
a. Type 1: This subtype is known as endometrioid carcinoma and is typically
associated with estrogen exposure. It tends to have a better prognosis and is often
diagnosed at an earlier stage.
b. Type 2: This subtype includes more aggressive forms of endometrial carcinoma,
such as serous carcinoma and clear cell carcinoma. Type 2 endometrial carcinomas are
less common but have a poorer prognosis.
2. Uterine sarcoma: Uterine sarcomas are rare and account for about 2-5% of uterine
cancers. They develop in the muscle or other tissues of the uterus. Uterine sarcomas
can be further classified into different subtypes, including leiomyosarcoma,
Endometrial stromal sarcoma, and Undifferentiated sarcoma.
The grade of an endometrial cancer is based on how much the cancer cells are organized into glands that look like the glands found in a
normal, healthy endometrium.In lower-grade cancers (grades 1 and 2), more of the cancer cells form glands. In higher-grade cancers (grade 3),
more of the cancer cells are disorganized and do not form glands.
• Grade 1 tumors have 95% or more of the cancer tissue forming glands.
• Grade 2 tumors have between 50% and 94% of the cancer tissue forming glands.
• Grade 3 tumors have less than half of the cancer tissue forming glands.
Grade 3 cancers tend to be aggressive (they grow and spread fast) and have a worse outlook than lower-grade cancers.Grades 1 and 2
endometrioid cancers are type 1 endometrial cancers.
Type 1 cancers are usually not very aggressive and they don't spread to other tissues quickly.Type 1 endometrial cancersare thought to be caused
by too much estrogen.They sometimes develop from atypical hyperplasia, an abnormal overgrowth of cells in the endometrium.
A small number of endometrial cancers are type 2 endometrial cancer. Type 2 cancers are more likely to grow and spread outside the uterus,
they have a poorer outlook (than type 1 cancers). Doctors tend to treat these cancers more aggressively. They don’t seem to be caused by too
much estrogen.
Type 2 cancers include all endometrial carcinomas that aren’t type 1, such as papillary serous carcinoma, clearcell carcinoma, undifferentiated
carcinoma, and grade 3 endometrioid carcinoma. These cancers don’t look at all like normal endometrium and so are called poorly differentiated
or high-grade.
CLASSIFICATION OF UTERINE CANCER
TNM Categories
T categories:
- TX: Primary tumor cannot be assessed.
- T0: No evidence of primary tumor.
- T1: Tumor is confined to the uterus.
- T1a: Tumor is limited to the endometrium (inner lining of the uterus).
- T1b: Tumor involves less than half of the myometrium (muscle layer of the uterus).
- T1c: Tumor involves more than half of the myometrium.
- T2: Tumor involves the cervix but does not extend beyond the uterus.
- T3: Tumor extends beyond the uterus but not to the pelvic sidewall or the lower third of the
vagina.
- T4: Tumor invades the bladder or bowel, or extends to the pelvic sidewall or the lower third
of the vagina.
N categories:
- NX: Regional lymph nodes cannot be assessed.
- N0: No regional lymph node metastasis.
- N1: Regional lymph node metastasis.
M categories:
- MX: Distant metastasis cannot be assessed.
- M0: No distant metastasis.
- M1: Distant metastasis present.
TNM CATEGORIES OF UTERINE CANCER
The stages of endometrial cancer using the FIGO system
Stage I: The cancer is found only in the uterus or womb, and it has not spread to other parts of the body.
Stage IA: The cancer is found only in the endometrium or has penetrated through less than one-half of the myometrium.
Stage IB: The tumor has spread to one-half or more of the myometrium.
Stage II: The tumor has spread from the uterus to the cervical stroma (the supportive tissues around the cervix) but not to other parts of the body.
Stage III: The cancer has spread beyond the uterus, but it is still only in the pelvic area.
Stage IIIA: The cancer has spread to the serosa of the uterus and/or the tissue of the fallopian tubes and ovaries but not to other parts of the body.
Stage IIIB: The tumor has spread to the vagina or to the tissue immediately next to the uterus called the parametrium.
Stage IIIC1: The cancer has spread to the regional pelvic lymph nodes. Lymph nodes are small, bean-shaped organs that help fight infection.
Stage IIIC2: The cancer has spread to the para-aortic lymph nodes with or without spread to the regional pelvic lymph nodes.
Stage IV: The cancer has metastasized to the rectum, bladder, and/or distant organs.
Stage IVA: The cancer has spread to the mucosa of the rectum or bladder.
Stage IVB: The cancer has spread to lymph nodes in the groin area, and/or it has spread to distant organs, such as the bones or lungs.
STAGING OF UTERINE CANCER
Uterine cancer can present with a variety of signs and symptoms, although some women may not experience any symptoms
in the early stages.
• Abnormal vaginal bleeding: About 90% of women with endometrial cancer have abnormal vaginal bleeding. This
might be a change in their periods, bleeding between periods, or bleeding after menopause. Non-bloody vaginal
discharge may also be a sign of endometrial cancer.
• Pelvic pain or discomfort: Some women with uterine cancer may experience pelvic pain or discomfort. This can range
from mild to severe and may be constant or intermittent.
• Changes in urinary or bowel habits: Uterine cancer can sometimes cause changes in urinary or bowel habits. This may
include increased frequency of urination, difficulty urinating, pain during urination, blood in the urine, constipation, or
changes in bowel movements.
• Pain during intercourse: Some women with uterine cancer may experience pain or discomfort during sexual
intercourse.
• Unexplained weight loss: In some cases, uterine cancer can cause unexplained weight loss, even without changes in
appetite or diet.
SIGN & SYMPTOMS OF UTERINE CANCER
1. Anamnesis morbi and vitae.
it is important for the examiner to determine the patient’s age and to obtain a reproductive history, including age at menarche, age at menopause,
and history of pregnancies including age at first full-term pregnancy. In premenopausal women, a recent history of pregnancy and lactation
should be noted. The history should include any use of HRT (Hormone replacement therapy) or use of hormones for contraception.
2. Physical Examination.
The physical exam will include a pelvic examination, which involves checking the vagina, cervix and uterus for signs of disease. feelling the
abdomen (belly) to check for swelling and any masses. To check the uterus, place two fingers inside the vagina while pressing on the abdomen
with their other hand. there may be also a vaginal or cervical examination using a speculum, an instrument that separates the walls of the vagina.
3. Ultrasound is often one of the first tests used to look at the uterus, ovaries, and fallopian tubes in women with possible gynecologic
problems. For a pelvic ultrasound, the transducer is moved over the skin of the lower part of the belly (abdomen). Often, to get good pictures
of the uterus, ovaries, and fallopian tubes, the bladder needs be full. That's why women getting a pelvic ultrasound are asked to drink lots of
water before the test. A transvaginal ultrasound(TVUS) is often better to look at the uterus. For this test, the TVUS probe (that works the same
way as the ultrasound transducer) is put into the vagina. Images from the TVUS can be used to see if the uterus contains a mass (tumor), or if
the endometrium is thicker than usual, which can be a sign of endometrial cancer. It may also help see if cancer is growing into the muscle
layer of the uterus (myometrium). A small tube may be used to put salt water (saline) into the uterus before the ultrasound. This helps the
doctor see the uterine lining more clearly. This procedure is called a saline infusion sonogram or hysterosonogram. (Sonogram is another term
for ultrasound.) Ultrasound can be used to see endometrial polyps (growths) , measure how thick the endometrium is, and can help doctors
pinpoint the area they want to biopsy.
DIAGNOSIS OF UTERINE CANCER
Power Doppler ultrasound images of endometrioid tumors of different stages and grades: (a) Stage IA,
Grade 1; (b) Stage IA, Grade 2; (c) Stage IA, Grade 3; (d) Stage IB, Grade 1; (e) Stage II, Grade 3.
4. Endometrial biopsy : An endometrial biopsy is the most commonly used test for endometrial cancer and is very accurate
in postmenopausal women. It can be done in the doctor's office. A very thin, flexible tube is put into the uterus through the
cervix. Then, using suction, a small amount of endometrium is removed through the tube. The suctioning takes about a
minute or less. The discomfort is a lot like menstrual cramps and can be helped by taking a nonsteroidal anti-inflammatory
drug (like ibuprofen) before the procedure. Sometimes a thin needle is used to inject numbing medicine (local anesthetic)
into the cervix just before the procedure to help reduce the pain.
5. Imaging tests: Imaging tests such as computed tomography (CT) scan, magnetic resonance imaging (MRI), or positron
emission tomography (PET) scan may be used to determine the extent of the cancer and whether it has spread to other parts
of the body.
laboratory investigation
1. Complete blood count: The complete blood count (CBC) is a test that measures different cells in the blood, such as the
red blood cells, the white blood cells, and the platelets. Endometrial cancer can cause bleeding, which can lead to low red
blood cell counts
CA-125 blood test: CA-125 is a substance released into the bloodstream by many, but not all, endometrial and ovarian
cancers. If a woman has endometrial cancer, a very high blood CA-125 level suggests that the cancer has likely spread
beyond the uterus. Some doctors check CA-125 levels before surgery or other treatment. If they're elevated, they can be
checked again to see how well the treatment is working (levels will drop after surgery if all the cancer is removed).
CA-125 levels are not needed to diagnose endometrial cancer, so this test isn’t done on all patients.
DIAGNOSIS OF UTERINE CANCER
Different types of treatment are available for patients with endometrial cancer. Some treatments are standard (the currently
used treatment), and some are being tested in clinical trials.
Surgery: Surgery (removing the cancer in an operation) is the most common treatment for endometrial cancer. The
following surgical procedures may be used:
• Total hysterectomy: Surgery to remove the uterus, including the cervix. If the uterus and cervix are taken out through the
vagina, the operation is called a vaginal hysterectomy. If the uterus and cervix are taken out through a large incision (cut)
in the abdomen, the operation is called a total abdominal hysterectomy. If the uterus and cervix are taken out through a
small incision (cut) in the abdomen using a laparoscope, the operation is called a total laparoscopic hysterectomy.
• Bilateral salpingo-oophorectomy: Surgery to remove both ovaries and both fallopian tubes.
• Radical hysterectomy: Surgery to remove the uterus, cervix, and part of the vagina. The ovaries, fallopian tubes, or
nearby lymph nodes may also be removed.
• Lymph node dissection: A surgical procedure in which the lymph nodes are removed from the pelvic area and a sample
of tissue is checked under a microscope for signs of cancer. This procedure is also called lymphadenectomy.
TREATMENT OF UTERINE CANCER
Abdominal hysterectomy performed through a low transverse incision, or
through a midline incision. This depends on the indication and the size of
the uterus – for example, a large fibroid uterus may necessitate a midline
incision.
The steps for a simple total hysterectomy, after the abdomen is opened
are as follows:
• The round ligaments are divided.
• If the tubes and ovaries are to be removed, the infundibulopelvic
ligaments are ligated and tied (the ureters should be identified first).
• The uterovesical peritoneal fold is divided and the bladder reflected
down past the cervix.
• The parametrial tissue is divided.
• The uterine vessels and ligated and tied.
• The paracervical tissue and uterosacral ligaments are ligated and tied.
• The vagina is opened and the uterus and cervix removed.
• The vagina is usually closed with an absorbable suture.
• Haemostasis is confirmed at all pedicles.
• The abdomen is closed.
TREATMENT
Radiation therapy uses high-energy radiation (like x-rays) to kill cancer cells. It can be
given in 2 ways to treat endometrial cancer:
By putting radioactive materials inside the body. This is called internal radiation therapy
or brachytherapy. By using a machine that focuses beams of radiation at the tumor, much
like having an x-ray. This is called external beam radiation therapy. In some cases,
both brachytherapy and external beam radiation therapy are used. When that's done, the
external beam radiation is usually given first, followed by the brachytherapy. The stage
and grade of the cancer are used to help decide what areas need to be treated with
radiation therapy and which types of radiation are used.Radiation is most often used
after surgery to treat endometrial cancer. It can kill any cancer cells that may still be in
the treated area. If your treatment plan includes radiation after surgery, you will be given
time to heal before starting radiation. Often, at least 4 to 6 weeks are needed.
Less often, radiation might be given before surgery to help shrink a tumor so it's easier to
remove.
Women who are not healthy enough for surgery may get radiation as their main
treatment.
TREATMENT OF UTERINE CANCER
Chemotherapy is the use of drugs that kill cancer cells. They're given into a vein
or taken by mouth as pills. These drugs go into the bloodstream and reach
throughout the body. Because of this, chemo is often part of the treatment when
endometrial cancer has spread beyond the endometrium to other parts of the body
and surgery can't be done. While chemo is not usually used to treat (early) stage I
and II endometrial cancers, chemo is commonly used for high grade cancers, which
grow and spread quickly, and cancer that comes back after treatment. This can
include early stage cancers of the high grade type. In most cases, a combination of
chemo drugs is used. Combination chemotherapy tends to work better than one
drug alone. Chemo is often given in cycles: a period of treatment, followed by a
rest period. The chemo drugs may be given on one or more days in each cycle.
Chemo drugs used to treat endometrial cancer may include:
• Paclitaxel (Taxol®)
• Carboplatin
• Doxorubicin (Adriamycin®) or liposomal doxorubicin (Doxil®)
• Cisplatin
• Docetaxel (Taxotere®)
Most often, 2 or more drugs are combined for treatment. The most common
combinations include carboplatin/paclitaxel and cisplatin/doxorubicin. Less often,
carboplatin/docetaxel and cisplatin/paclitaxel/doxorubicin may be used.
TREATMENT OF UTERINE CANCER
Hormone Therapy for Endometrial Cancer This type of treatment uses hormones or hormone-blocking drugs to treat cancer. It’s not the same
as the hormone therapy given to ease the symptoms of menopause (menopausal hormone therapy). It's most often used to treat endometrial
cancer that's advanced (stage III or IV) or has come back after treatment (recurred). Hormone therapy is often used along with chemotherapy.
Hormone treatment for endometrial cancer can include:
• Progestins (This is the main hormone treatment used.)
• Tamoxifen
At this time, no one type of hormone treatment has been found to be the best for endometrial cancer.
Targeted therapy : is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells. Targeted therapies
usually cause less harm to normal cells than chemotherapy or radiation therapy do. Monoclonal antibodies, mTOR inhibitors, and signal
transduction inhibitors are three types of targeted therapy used to treat endometrial cancer.
Monoclonal antibody therapy: Monoclonal antibodies are immune system proteins made in the laboratory to treat many diseases, including
cancer. As a cancer treatment, these antibodies can attach to a specific target on cancer cells or other cells that may help cancer cells grow. The
antibodies are able to then kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion.
They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells. Bevacizumab is used to treat stage III, stage IV,
and recurrent endometrial cancer.
mTOR inhibitor therapy: mTOR inhibitors block a protein called mTOR, which helps control cell division. mTOR inhibitors may keep cancer
cells from growing and prevent the growth of new blood vessels that tumors need to grow. Everolimus and ridaforolimus are used to treat stage
III, stage IV, and recurrent endometrial cancer.
Signal transduction inhibitor therapy: Signal transduction inhibitors block signals that are passed from one molecule to another inside a cell.
Blocking these signals may kill cancer cells. Metformin is being studied to treat stage III, stage IV, and recurrent endometrial cancer.
• Luteinizing hormone-releasing hormone agonists (LHRH agonists)
• Aromatase inhibitors (AIs)
TREATMENT OF UTERINE CANCER
• Oxford Handbook of Oncology
• Alektiar KM, Abu-Rustum NR, Fleming GF. Cancer of the uterine body. In: DeVita VT, Hellman S, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg‘s
Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2015: 1048-1064.
• Alvarez EA, Brady WE, Walker JL, et al. Phase II trial of combination bevacizumab and temsirolimus in the treatment of recurrent or persistent endometrial
carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2013;129(1):22-27.
• Amant F, Moerman P, Neven P, et al. Endometrial cancer. Lancet. 2005; 366:491-505.Aromatase inhibitors (AIs)
• American Cancer Society. Cancer Treatment & Survivorship Facts & Figures 2014-2015. Atlanta, Ga: American Cancer Society; 2015.
• American College of Obstetricians and Gynecologists. ACOG practice bulletin, clinical management guidelines for obstetrician-gynecologists, number 65, August
2005: management of endometrial cancer. Obstet Gynecol. 2005;106(2):413-425.
• American Joint Committee on Cancer. Uterine Cancer. In: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010: 403-409.
• Barlin JN, Puri I, Bristow RE. Cytoreductive surgery for advanced or recurrent endometrial cancer: a meta-analysis. Gynecol Oncol. 2010;118(1):14-18.
• Beining RM, Dennis LK, Smith EM, Dokras A. Meta-analysis of intrauterine device use and risk of endometrial cancer. Ann Epidemiol. 2008;18:492-499.
• Creasman WT, Odicino F, Maisonneuve P, et al. Carcinoma of the corpus uteri. Int J Gynecol Obs. 2003;83:79-118.
• Emons G, Günthert A, Thiel FC, et al. Phase II study of fulvestrant 250 mg/month in patients with recurrent or metastatic endometrial cancer: a study of the
Arbeitsgemeinschaft Gynäkologische Onkologie. Gynecol Oncol. 2013;129(3):495-499.
• Freedman DM, Curtis RE, Travis LB, Fraumeni Jr JF. New Malignancies Following Cancer of the Uterine Corpus and Ovary. In: Curtis RE, Freedman DM, Ron E,
Ries LAG, Hacker DG, Edwards BK, Tucker MA, Fraumeni JF Jr. (eds). New Malignancies Among Cancer Survivors: SEER Cancer Registries, 1973-2000.
National Cancer Institute. NIH Publ. No. 05-5302. Bethesda, MD, 2006. Accessed on 4/18/2014 at
http://seer.cancer.gov/archive/publications/mpmono/MPMonograph_complete.pdf.
• Howlader N, Noone AM, Krapcho M, et al (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD,
http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.
REFERENCES
THANK YOU

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Oncology (Uterine Cancer)

  • 1. UTERINE CANCER ● University of Traditional Medicine Prepared by Ali Al-Hayali To Doctor Arsen Minasyan GM-603 Group roup ONCOLOGY
  • 2. The uterus is a hollow organ, normally about the size and shape of a medium-sized pear. The uterus is where a fetus grows and develops when a woman is pregnant. It has 2 main parts (see image below): • The upper part of the uterus is called the body or the corpus. • The cervix is the lower end of the uterus that joins it to the vagina. The body of the uterus has 2 main layers: • The myometrium is the outer layer. This thick layer of muscle is needed to push the baby out during birth. • The endometrium is the inner layer. During a woman's menstrual cycle, hormones cause the endometrium to change. Estrogen causes the endometrium to thicken so that it could nourish an embryo if pregnancy occurs. If there is no pregnancy, estrogen is produced in lower amounts and more of the hormone called progesterone is made. This causes the endometrial lining to shed from the uterus and become the menstrual flow (period). This cycle repeats until menopause. INTRODUCTION
  • 3. 1. Incidence: Uterine cancer is the fourth most common cancer and the sixth most common cause of death among women in the United States. It is the most frequent gynecologic cancer in the United States, with an estimated 66,200 new cases and 13,030 deaths in 2023 2. Age: Uterine cancer primarily affects postmenopausal women, with the highest incidence occurring between the ages of 50 and 70. However, it can also occur in younger women, especially those with certain risk factors. 3. Risk factors: Several factors increase the risk of developing uterine cancer, including obesity, hormonal imbalances (such as estrogen dominance), diabetes, hypertension, certain genetic conditions (such as Lynch syndrome), and a history of endometrial hyperplasia or polycystic ovary syndrome (PCOS). 4. Geographical variation: The incidence of uterine cancer varies across different regions and countries. It is more common in developed countries with higher rates of obesity and sedentary lifestyles. 5. Racial and ethnic disparities: Uterine cancer rates differ among racial and ethnic groups. In the United States, for example, African American women have higher incidence and mortality rates compared to other racial groups. 6. Survival rates: The prognosis for uterine cancer is generally favorable, especially when diagnosed at an early stage. The five-year survival rate for localized uterine cancer is around 95%. However, the prognosis worsens with advanced stages of the disease. EPIDEMIOLOGY OF UTERINE CANCER
  • 4. • Ovarian tumors: A certain type of ovarian tumor, the granulosa cell tumor, often makes estrogen. Estrogen made by one of these tumors isn't controlled the way hormone release from the ovaries is, and it can sometimes lead to high estrogen levels. The resulting hormone imbalance can stimulate the endometrium and even lead to endometrial cancer. • Polycystic ovarian syndrome: Women with a condition called polycystic ovarian syndrome (PCOS) have abnormal hormone levels, such as higher androgen (male hormones) and estrogen levels and lower levels of progesterone. The increase in estrogen relative to progesterone can increase a woman's chance of getting endometrial cancer. PCOS is also a leading cause of infertility in women. • Diet and exercise: A high-fat diet can increase the risk of many cancers, including endometrial cancer. Because fatty foods are also high- calorie foods, a high-fat diet can lead to obesity, which is a well-known endometrial cancer risk factor. Many scientists think this is the main way in which a high-fat diet raises endometrial cancer risk. Some scientists think that fatty foods may also have a direct effect on how the body uses estrogen, which increases endometrial cancer risk. Physical activity lowers the risk of endometrial cancer. Many studies have found that women who exercise more have a lower risk of endometrial cancer, while others • Diabetes: Endometrial cancer may be about twice as common in women with type 2 diabetes. But diabetes is more common in people who are overweight and less active, which are also risk factors for endometrial cancer. This makes it hard to find a clear link. • Family history: Endometrial cancer tends to run in some families. Some of these families also have a higher risk for colon cancer. This disorder is called hereditary nonpolyposis colon cancer (HNPCC). Another name for HNPCC is Lynch syndrome. In most cases, this disorder is caused by a defect in either the mismatch repair gene MLH1 or the geneMSH2. But at least 5 other genes can cause HNPCC: MLH3, MSH6, TGBR2, PMS1,and PMS2. An abnormal copy of any one of these genes reduces the body's ability to repair damage to its DNA or control cell growth. • Endometrial hyperplasia: Endometrial hyperplasia is an increased growth of the endometrium. Mild or simple hyperplasia, the most common type, has a very small risk of becoming cancer. If the hyperplasia is called “atypical,” it has a higher chance of becoming a cancer. • Prior pelvic radiation therapy: Radiation used to treat some other cancers can damage the DNA of cells, sometimes increasing the risk of a second type of cancer9 such as endometrial cancer. RISK FACTOR OF UTERINE CANCER
  • 5. Although certain factors can increase a woman's risk for endometrial cancer, they don't always cause the disease. Many women with risk factors never develop endometrial cancer. • Obesity: Obesity is a strong risk factor for endometrial cancer and linked to hormone changes, which are covered in more detail below.A woman's ovaries produce most of her estrogen before menopause. But fat tissue can change some other hormones (called androgens) into estrogens. This can impact estrogen levels, especially after menopause. Having more fat tissue can increase a woman's estrogen levels, which increases her endometrial cancer risk. • Hormone factors: A woman's hormone balance plays a part in the development of most endometrial cancers. Many of the risk factors for endometrial cancer affect estrogen levels. Before menopause, the ovaries are the major source of the 2 main types of female hormones are estrogen and progesterone. The balance between these hormones changes each month during a woman's menstrual cycle. This produces a woman's monthly periods and keeps the endometrium healthy. A shift in the balance of these hormones toward more estrogen increases a woman's risk for endometrial cancer. After menopause, the ovaries stop making these hormones, but a small amount of estrogen is still made naturally in fat tissue. Estrogen from fat tissue has a bigger impact after menopause than it does before menopause. • Estrogen therapy: Estrogen treatment can help reduce hot flashes, improve vaginal dryness, and help prevent the weakening of the bones (osteoporosis) that can occur with menopause. But using estrogen alone (without progesterone) can lead to endometrial cancer in women who still have a uterus. • Total number of menstrual cycles: Having more menstrual cycles during a woman's lifetime raises her risk of endometrial cancer. Starting menstrual periods (menarche) before age 12 and/or going through menopause later in life raises the risk. Pregnancy: The hormonal balance shifts toward more progesterone during pregnancy. So having many pregnancies helps protect against endometrial cancer. Women who have never been pregnant have a higher risk, especially if they were also infertile (unable to become pregnant). Tamoxifen: Tamoxifen is a drug that is used to help prevent and treatbreast cancer. Tamoxifen acts as an anti-estrogen in breast tissue, but it acts like an estrogen in the uterus. In women who have gone through menopause, it can cause the uterine lining to grow, which increases the risk of endometrial cancer. The risk of developing endometrial cancer from tamoxifen is low (less than 1% per year). RISK FACTOR OF UTERINE CANCER
  • 6. CLASSIFICATION OF UTERINE CANCER Uterine cancer can be classified into different types based on the specific cells involved and their characteristics. The two main types of uterine cancer are: 1. Endometrial carcinoma: This is the most common type of uterine cancer, accounting for about 80-90% of cases. It originates in the cells lining the uterus, known as the endometrium. Occurs principally in post-menopausal women, and the incidence rises with age. Also Commoner in obese women, in whom oestrogen is peripherally produced in fat. Classified into two subtypes: a. Type 1: This subtype is known as endometrioid carcinoma and is typically associated with estrogen exposure. It tends to have a better prognosis and is often diagnosed at an earlier stage. b. Type 2: This subtype includes more aggressive forms of endometrial carcinoma, such as serous carcinoma and clear cell carcinoma. Type 2 endometrial carcinomas are less common but have a poorer prognosis. 2. Uterine sarcoma: Uterine sarcomas are rare and account for about 2-5% of uterine cancers. They develop in the muscle or other tissues of the uterus. Uterine sarcomas can be further classified into different subtypes, including leiomyosarcoma, Endometrial stromal sarcoma, and Undifferentiated sarcoma.
  • 7. The grade of an endometrial cancer is based on how much the cancer cells are organized into glands that look like the glands found in a normal, healthy endometrium.In lower-grade cancers (grades 1 and 2), more of the cancer cells form glands. In higher-grade cancers (grade 3), more of the cancer cells are disorganized and do not form glands. • Grade 1 tumors have 95% or more of the cancer tissue forming glands. • Grade 2 tumors have between 50% and 94% of the cancer tissue forming glands. • Grade 3 tumors have less than half of the cancer tissue forming glands. Grade 3 cancers tend to be aggressive (they grow and spread fast) and have a worse outlook than lower-grade cancers.Grades 1 and 2 endometrioid cancers are type 1 endometrial cancers. Type 1 cancers are usually not very aggressive and they don't spread to other tissues quickly.Type 1 endometrial cancersare thought to be caused by too much estrogen.They sometimes develop from atypical hyperplasia, an abnormal overgrowth of cells in the endometrium. A small number of endometrial cancers are type 2 endometrial cancer. Type 2 cancers are more likely to grow and spread outside the uterus, they have a poorer outlook (than type 1 cancers). Doctors tend to treat these cancers more aggressively. They don’t seem to be caused by too much estrogen. Type 2 cancers include all endometrial carcinomas that aren’t type 1, such as papillary serous carcinoma, clearcell carcinoma, undifferentiated carcinoma, and grade 3 endometrioid carcinoma. These cancers don’t look at all like normal endometrium and so are called poorly differentiated or high-grade. CLASSIFICATION OF UTERINE CANCER
  • 8. TNM Categories T categories: - TX: Primary tumor cannot be assessed. - T0: No evidence of primary tumor. - T1: Tumor is confined to the uterus. - T1a: Tumor is limited to the endometrium (inner lining of the uterus). - T1b: Tumor involves less than half of the myometrium (muscle layer of the uterus). - T1c: Tumor involves more than half of the myometrium. - T2: Tumor involves the cervix but does not extend beyond the uterus. - T3: Tumor extends beyond the uterus but not to the pelvic sidewall or the lower third of the vagina. - T4: Tumor invades the bladder or bowel, or extends to the pelvic sidewall or the lower third of the vagina. N categories: - NX: Regional lymph nodes cannot be assessed. - N0: No regional lymph node metastasis. - N1: Regional lymph node metastasis. M categories: - MX: Distant metastasis cannot be assessed. - M0: No distant metastasis. - M1: Distant metastasis present. TNM CATEGORIES OF UTERINE CANCER
  • 9. The stages of endometrial cancer using the FIGO system Stage I: The cancer is found only in the uterus or womb, and it has not spread to other parts of the body. Stage IA: The cancer is found only in the endometrium or has penetrated through less than one-half of the myometrium. Stage IB: The tumor has spread to one-half or more of the myometrium. Stage II: The tumor has spread from the uterus to the cervical stroma (the supportive tissues around the cervix) but not to other parts of the body. Stage III: The cancer has spread beyond the uterus, but it is still only in the pelvic area. Stage IIIA: The cancer has spread to the serosa of the uterus and/or the tissue of the fallopian tubes and ovaries but not to other parts of the body. Stage IIIB: The tumor has spread to the vagina or to the tissue immediately next to the uterus called the parametrium. Stage IIIC1: The cancer has spread to the regional pelvic lymph nodes. Lymph nodes are small, bean-shaped organs that help fight infection. Stage IIIC2: The cancer has spread to the para-aortic lymph nodes with or without spread to the regional pelvic lymph nodes. Stage IV: The cancer has metastasized to the rectum, bladder, and/or distant organs. Stage IVA: The cancer has spread to the mucosa of the rectum or bladder. Stage IVB: The cancer has spread to lymph nodes in the groin area, and/or it has spread to distant organs, such as the bones or lungs. STAGING OF UTERINE CANCER
  • 10.
  • 11. Uterine cancer can present with a variety of signs and symptoms, although some women may not experience any symptoms in the early stages. • Abnormal vaginal bleeding: About 90% of women with endometrial cancer have abnormal vaginal bleeding. This might be a change in their periods, bleeding between periods, or bleeding after menopause. Non-bloody vaginal discharge may also be a sign of endometrial cancer. • Pelvic pain or discomfort: Some women with uterine cancer may experience pelvic pain or discomfort. This can range from mild to severe and may be constant or intermittent. • Changes in urinary or bowel habits: Uterine cancer can sometimes cause changes in urinary or bowel habits. This may include increased frequency of urination, difficulty urinating, pain during urination, blood in the urine, constipation, or changes in bowel movements. • Pain during intercourse: Some women with uterine cancer may experience pain or discomfort during sexual intercourse. • Unexplained weight loss: In some cases, uterine cancer can cause unexplained weight loss, even without changes in appetite or diet. SIGN & SYMPTOMS OF UTERINE CANCER
  • 12. 1. Anamnesis morbi and vitae. it is important for the examiner to determine the patient’s age and to obtain a reproductive history, including age at menarche, age at menopause, and history of pregnancies including age at first full-term pregnancy. In premenopausal women, a recent history of pregnancy and lactation should be noted. The history should include any use of HRT (Hormone replacement therapy) or use of hormones for contraception. 2. Physical Examination. The physical exam will include a pelvic examination, which involves checking the vagina, cervix and uterus for signs of disease. feelling the abdomen (belly) to check for swelling and any masses. To check the uterus, place two fingers inside the vagina while pressing on the abdomen with their other hand. there may be also a vaginal or cervical examination using a speculum, an instrument that separates the walls of the vagina. 3. Ultrasound is often one of the first tests used to look at the uterus, ovaries, and fallopian tubes in women with possible gynecologic problems. For a pelvic ultrasound, the transducer is moved over the skin of the lower part of the belly (abdomen). Often, to get good pictures of the uterus, ovaries, and fallopian tubes, the bladder needs be full. That's why women getting a pelvic ultrasound are asked to drink lots of water before the test. A transvaginal ultrasound(TVUS) is often better to look at the uterus. For this test, the TVUS probe (that works the same way as the ultrasound transducer) is put into the vagina. Images from the TVUS can be used to see if the uterus contains a mass (tumor), or if the endometrium is thicker than usual, which can be a sign of endometrial cancer. It may also help see if cancer is growing into the muscle layer of the uterus (myometrium). A small tube may be used to put salt water (saline) into the uterus before the ultrasound. This helps the doctor see the uterine lining more clearly. This procedure is called a saline infusion sonogram or hysterosonogram. (Sonogram is another term for ultrasound.) Ultrasound can be used to see endometrial polyps (growths) , measure how thick the endometrium is, and can help doctors pinpoint the area they want to biopsy. DIAGNOSIS OF UTERINE CANCER
  • 13. Power Doppler ultrasound images of endometrioid tumors of different stages and grades: (a) Stage IA, Grade 1; (b) Stage IA, Grade 2; (c) Stage IA, Grade 3; (d) Stage IB, Grade 1; (e) Stage II, Grade 3.
  • 14. 4. Endometrial biopsy : An endometrial biopsy is the most commonly used test for endometrial cancer and is very accurate in postmenopausal women. It can be done in the doctor's office. A very thin, flexible tube is put into the uterus through the cervix. Then, using suction, a small amount of endometrium is removed through the tube. The suctioning takes about a minute or less. The discomfort is a lot like menstrual cramps and can be helped by taking a nonsteroidal anti-inflammatory drug (like ibuprofen) before the procedure. Sometimes a thin needle is used to inject numbing medicine (local anesthetic) into the cervix just before the procedure to help reduce the pain. 5. Imaging tests: Imaging tests such as computed tomography (CT) scan, magnetic resonance imaging (MRI), or positron emission tomography (PET) scan may be used to determine the extent of the cancer and whether it has spread to other parts of the body. laboratory investigation 1. Complete blood count: The complete blood count (CBC) is a test that measures different cells in the blood, such as the red blood cells, the white blood cells, and the platelets. Endometrial cancer can cause bleeding, which can lead to low red blood cell counts CA-125 blood test: CA-125 is a substance released into the bloodstream by many, but not all, endometrial and ovarian cancers. If a woman has endometrial cancer, a very high blood CA-125 level suggests that the cancer has likely spread beyond the uterus. Some doctors check CA-125 levels before surgery or other treatment. If they're elevated, they can be checked again to see how well the treatment is working (levels will drop after surgery if all the cancer is removed). CA-125 levels are not needed to diagnose endometrial cancer, so this test isn’t done on all patients. DIAGNOSIS OF UTERINE CANCER
  • 15. Different types of treatment are available for patients with endometrial cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. Surgery: Surgery (removing the cancer in an operation) is the most common treatment for endometrial cancer. The following surgical procedures may be used: • Total hysterectomy: Surgery to remove the uterus, including the cervix. If the uterus and cervix are taken out through the vagina, the operation is called a vaginal hysterectomy. If the uterus and cervix are taken out through a large incision (cut) in the abdomen, the operation is called a total abdominal hysterectomy. If the uterus and cervix are taken out through a small incision (cut) in the abdomen using a laparoscope, the operation is called a total laparoscopic hysterectomy. • Bilateral salpingo-oophorectomy: Surgery to remove both ovaries and both fallopian tubes. • Radical hysterectomy: Surgery to remove the uterus, cervix, and part of the vagina. The ovaries, fallopian tubes, or nearby lymph nodes may also be removed. • Lymph node dissection: A surgical procedure in which the lymph nodes are removed from the pelvic area and a sample of tissue is checked under a microscope for signs of cancer. This procedure is also called lymphadenectomy. TREATMENT OF UTERINE CANCER
  • 16. Abdominal hysterectomy performed through a low transverse incision, or through a midline incision. This depends on the indication and the size of the uterus – for example, a large fibroid uterus may necessitate a midline incision. The steps for a simple total hysterectomy, after the abdomen is opened are as follows: • The round ligaments are divided. • If the tubes and ovaries are to be removed, the infundibulopelvic ligaments are ligated and tied (the ureters should be identified first). • The uterovesical peritoneal fold is divided and the bladder reflected down past the cervix. • The parametrial tissue is divided. • The uterine vessels and ligated and tied. • The paracervical tissue and uterosacral ligaments are ligated and tied. • The vagina is opened and the uterus and cervix removed. • The vagina is usually closed with an absorbable suture. • Haemostasis is confirmed at all pedicles. • The abdomen is closed. TREATMENT
  • 17. Radiation therapy uses high-energy radiation (like x-rays) to kill cancer cells. It can be given in 2 ways to treat endometrial cancer: By putting radioactive materials inside the body. This is called internal radiation therapy or brachytherapy. By using a machine that focuses beams of radiation at the tumor, much like having an x-ray. This is called external beam radiation therapy. In some cases, both brachytherapy and external beam radiation therapy are used. When that's done, the external beam radiation is usually given first, followed by the brachytherapy. The stage and grade of the cancer are used to help decide what areas need to be treated with radiation therapy and which types of radiation are used.Radiation is most often used after surgery to treat endometrial cancer. It can kill any cancer cells that may still be in the treated area. If your treatment plan includes radiation after surgery, you will be given time to heal before starting radiation. Often, at least 4 to 6 weeks are needed. Less often, radiation might be given before surgery to help shrink a tumor so it's easier to remove. Women who are not healthy enough for surgery may get radiation as their main treatment. TREATMENT OF UTERINE CANCER
  • 18. Chemotherapy is the use of drugs that kill cancer cells. They're given into a vein or taken by mouth as pills. These drugs go into the bloodstream and reach throughout the body. Because of this, chemo is often part of the treatment when endometrial cancer has spread beyond the endometrium to other parts of the body and surgery can't be done. While chemo is not usually used to treat (early) stage I and II endometrial cancers, chemo is commonly used for high grade cancers, which grow and spread quickly, and cancer that comes back after treatment. This can include early stage cancers of the high grade type. In most cases, a combination of chemo drugs is used. Combination chemotherapy tends to work better than one drug alone. Chemo is often given in cycles: a period of treatment, followed by a rest period. The chemo drugs may be given on one or more days in each cycle. Chemo drugs used to treat endometrial cancer may include: • Paclitaxel (Taxol®) • Carboplatin • Doxorubicin (Adriamycin®) or liposomal doxorubicin (Doxil®) • Cisplatin • Docetaxel (Taxotere®) Most often, 2 or more drugs are combined for treatment. The most common combinations include carboplatin/paclitaxel and cisplatin/doxorubicin. Less often, carboplatin/docetaxel and cisplatin/paclitaxel/doxorubicin may be used. TREATMENT OF UTERINE CANCER
  • 19. Hormone Therapy for Endometrial Cancer This type of treatment uses hormones or hormone-blocking drugs to treat cancer. It’s not the same as the hormone therapy given to ease the symptoms of menopause (menopausal hormone therapy). It's most often used to treat endometrial cancer that's advanced (stage III or IV) or has come back after treatment (recurred). Hormone therapy is often used along with chemotherapy. Hormone treatment for endometrial cancer can include: • Progestins (This is the main hormone treatment used.) • Tamoxifen At this time, no one type of hormone treatment has been found to be the best for endometrial cancer. Targeted therapy : is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells. Targeted therapies usually cause less harm to normal cells than chemotherapy or radiation therapy do. Monoclonal antibodies, mTOR inhibitors, and signal transduction inhibitors are three types of targeted therapy used to treat endometrial cancer. Monoclonal antibody therapy: Monoclonal antibodies are immune system proteins made in the laboratory to treat many diseases, including cancer. As a cancer treatment, these antibodies can attach to a specific target on cancer cells or other cells that may help cancer cells grow. The antibodies are able to then kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells. Bevacizumab is used to treat stage III, stage IV, and recurrent endometrial cancer. mTOR inhibitor therapy: mTOR inhibitors block a protein called mTOR, which helps control cell division. mTOR inhibitors may keep cancer cells from growing and prevent the growth of new blood vessels that tumors need to grow. Everolimus and ridaforolimus are used to treat stage III, stage IV, and recurrent endometrial cancer. Signal transduction inhibitor therapy: Signal transduction inhibitors block signals that are passed from one molecule to another inside a cell. Blocking these signals may kill cancer cells. Metformin is being studied to treat stage III, stage IV, and recurrent endometrial cancer. • Luteinizing hormone-releasing hormone agonists (LHRH agonists) • Aromatase inhibitors (AIs) TREATMENT OF UTERINE CANCER
  • 20. • Oxford Handbook of Oncology • Alektiar KM, Abu-Rustum NR, Fleming GF. Cancer of the uterine body. In: DeVita VT, Hellman S, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg‘s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2015: 1048-1064. • Alvarez EA, Brady WE, Walker JL, et al. Phase II trial of combination bevacizumab and temsirolimus in the treatment of recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2013;129(1):22-27. • Amant F, Moerman P, Neven P, et al. Endometrial cancer. Lancet. 2005; 366:491-505.Aromatase inhibitors (AIs) • American Cancer Society. Cancer Treatment & Survivorship Facts & Figures 2014-2015. Atlanta, Ga: American Cancer Society; 2015. • American College of Obstetricians and Gynecologists. ACOG practice bulletin, clinical management guidelines for obstetrician-gynecologists, number 65, August 2005: management of endometrial cancer. Obstet Gynecol. 2005;106(2):413-425. • American Joint Committee on Cancer. Uterine Cancer. In: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010: 403-409. • Barlin JN, Puri I, Bristow RE. Cytoreductive surgery for advanced or recurrent endometrial cancer: a meta-analysis. Gynecol Oncol. 2010;118(1):14-18. • Beining RM, Dennis LK, Smith EM, Dokras A. Meta-analysis of intrauterine device use and risk of endometrial cancer. Ann Epidemiol. 2008;18:492-499. • Creasman WT, Odicino F, Maisonneuve P, et al. Carcinoma of the corpus uteri. Int J Gynecol Obs. 2003;83:79-118. • Emons G, Günthert A, Thiel FC, et al. Phase II study of fulvestrant 250 mg/month in patients with recurrent or metastatic endometrial cancer: a study of the Arbeitsgemeinschaft Gynäkologische Onkologie. Gynecol Oncol. 2013;129(3):495-499. • Freedman DM, Curtis RE, Travis LB, Fraumeni Jr JF. New Malignancies Following Cancer of the Uterine Corpus and Ovary. In: Curtis RE, Freedman DM, Ron E, Ries LAG, Hacker DG, Edwards BK, Tucker MA, Fraumeni JF Jr. (eds). New Malignancies Among Cancer Survivors: SEER Cancer Registries, 1973-2000. National Cancer Institute. NIH Publ. No. 05-5302. Bethesda, MD, 2006. Accessed on 4/18/2014 at http://seer.cancer.gov/archive/publications/mpmono/MPMonograph_complete.pdf. • Howlader N, Noone AM, Krapcho M, et al (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014. REFERENCES