What is endometrial cancer?

Endometrial cancer develops when cells in the endometrium begin to grow out of control and can then invade nearby tissues or spread throughout the body. Large collections of this out of control tissue are called tumors. However, some tumors are not really cancer because they cannot spread or threaten someone's life. These are called benign tumors.

The tumors that can spread throughout the body or invade nearby tissues are considered cancer and are called malignant tumors. The distinction between benign and malignant tumors is very important in uterine cancer because there are many benign processes affecting the uterus that may get confused with cancers. Fibroids are very common, benign tumors of the uterus that are not cancerous. They can occasionally cause increased vaginal bleeding, vaginal discharge, or pain. Your doctor may suggest that you have fibroids removed if they are becoming bothersome.

Cancers are characterized by the normal cells from which they form. The most common type of endometrial cancer is called endometrioid adenocarcinoma; it comes from cells that form glands in the endometrium and it has a characteristic appearance under the microscope. Endometrioid endometrial cancer compromises about 75-80% of all endometrial cancers. The second most common form is papillary serous adenocarcinoma (about 10% of all endometrial cancers) and another form is clear cell adenocarcinoma (about 4-5% of all endometrial carcinomas).

Both papillary serous and clear cell adenocarcinomas tend to be more aggressive than endometrioid adenocarcinomas, and are often detected at advanced stages. Sometimes an endometrial cancer has features of more than one subtype; this is called a mixed adenocarcinoma and they make up about 10% of all endometrial cancers. There are a few other rare types like mucinous adenocarcinoma and squamous cell adenocarcinoma that each compromise less than 1% of endometrial cancers.

Am I at risk for endometrial cancer?

Endometrial cancer is the most common gynecologic cancer in the United States. In the U.S., it is expected that 39,300 women will develop endometrial cancer in 2002; and 6,600 women will die of endometrial cancer in 2002. This makes endometrial cancer the 4th most common female cancer and the 8th most common cause of cancer death in women in the U.S.. The majority of women diagnosed with endometrial cancer have already gone through menopause, although it can occur in younger women as well. The average age of diagnosis is 63, and the peak incidence is between the ages of 70 and 74.

Although there are several known risk factors for getting endometrial cancer, no one knows exactly why one woman gets it and another doesn't. One of the risk factors for developing endometrial cancer is age; the older a woman becomes, the higher her chances are of getting it. It appears that the amount of estrogen that a woman is exposed to in her lifetime influences her chances of contracting endometrial cancer. Women who are exposed to more estrogen, either naturally or from outside sources, are more likely to develop endometrial cancer. Thus any factor that causes a woman to have high levels of estrogen is also a risk factor for endometrial cancer.

The more menstrual cycles a woman has in her lifetime, the more estrogen her endometrium is exposed. Women who started menstruating early, go through menopause late, don't have any children, don't breastfeed or don't use a form of birth control that stops ovulation (like birth control pills) are more likely to develop endometrial cancer. Another condition that increases estrogen in a woman's body is obesity. Fat tissue converts other hormones into estrogens, so extremely overweight people have higher levels of estrogen than thin people. This means that obesity is also a risk factor for endometrial cancer. Diabetes (which also tends to occur in obese people) seems to be a risk factor for endometrial cancer as well.

Women who take hormone replacement therapy (HRT) after menopause are at a slightly increased risk for endometrial cancer. Tamoxifen is a drug that is used in women with breast cancer to decrease their risk of a cancer recurrence. Because it has estrogen-like properties, the use of tamoxifen is linked to higher rates of endometrial cancer. However, the danger is relatively small and it is prescribed because the benefits of taking tamoxifen (in terms of breast cancer prevention) outweigh the minor increased risks of developing endometrial cancer.

Another risk factor for endometrial cancer is a family history of endometrial cancer. A small percentage of women who get endometrial cancer carry a genetic mutation that causes a syndrome that increases their risk. The Lynch Syndrome is associated with colon and endometrial cancers (it is also called hereditary nonpolyposis colorectal cancer syndrome - HNPCC), Women can inherit a mutation from their parents and it may be worth testing for mutations if a woman has a particularly strong family history of endometrial or colon cancer (meaning multiple relatives affected, especially if they are under 50 years old when they get the disease).

Having a mutation doesn't necessarily mean a woman is going to get the disease, but it does greatly increase her chances above the general population. Family members may elect to get tested to see if they carry mutations as well. If a woman does have the mutation, she can get more rigorous screening or even undergo a prophylactic hysterectomy (preventive removal of your uterus) to decrease her chances of contracting cancer. The decision to get tested is a highly personal one that should be discussed with a doctor who is trained in counseling patients about genetic testing.

It has been demonstrated that a diet high in animal fats and low in fruits and vegetables can increase your risk for endometrial cancer. Remember that all risk factors are based on probabilities, and even someone without any risk factors can still get endometrial cancer. Talk to your doctor about your risk factors for endometrial cancer to understand his/her recommendations for screening and prevention.

How can I prevent endometrial cancer?

Unfortunately, there aren't very good screening methods for endometrial cancer, so preventing it is a particularly important challenge. If you are a woman without a family history/genetic syndrome, then the best way to prevent endometrial cancer is to alter whatever risk factors you have control over. Consider using methods of birth control (like OCPs - oral contraceptive pills, or depo-provera) that stop ovulation/menstruation. Multiple studies have demonstrated that OCPs reduce a woman's risk for developing endometrial cancer; the longer a woman takes them, the more they help in this regard. If you plan to get pregnant, try and do so before age 30. If you are obese, try and lose those extra pounds.

Women who are carriers of Lynch Syndrome, the above mentioned genetic syndrome, face different decisions. They generally need to have more rigorous screening done for endometrial cancer, and some of them may elect to have their uterus's removed when they are still healthy (called a prophylactic hysterectomy). This should only be done when a woman is finished having children, and it can eliminate the possibility that a woman will contract endometrial cancer. Before a woman decides to do this, she should have genetic testing and a significant amount of counseling from a physician who has experience with genetic diseases.

Another time that some women will be offered a prophylactic hysterectomy is if they are done having children, have already gone through menopause, and are taking estrogens as a part of hormone replacement therapy. Discuss your options with your doctors to best sort out the different methods of preventing endometrial cancer in your particular case.

While a diet high in animal fats has been implicated in endometrial cancer, a diet rich in fruits and vegetables may have a small preventive effect. It has been suggested that diets high in naturally occurring phytoestrogens (which are prevalent in soy products) and fatty fishes may decrease your risk, but further studies need to be performed before these particular nutritional recommendations can be made regarding endometrial cancer prevention.

What screening tests are available?

Patients who are diagnosed with early endometrial cancers tend to respond to treatment better than patients with more advanced cancers, so it is beneficial to detect endometrial cancers as early as possible. Luckily, many endometrial cancers are found at early stages, because early endometrial cancers often cause vaginal bleeding (which is very abnormal in post-menopausal women). When post-menopausal women experience vaginal bleeding, they are often worried enough to see their physicians who can then use more invasive tests to look for endometrial cancers.

Right now, there aren't any endometrial cancer screening recommendations for the general population (women without hereditary cancer syndromes) because there aren't any effective screening tests available. Women should get annual pelvic exams for cervical and ovarian cancer screening, but endometrial cancer is not routinely screened for in the general population.

Women with a strong family history and many risk factors or who have a proven hereditary cancer syndrome may need to get rigorous screening for endometrial cancer. Currently, the American Cancer Society recommends that women with Lynch Syndrome (HNPCC) get annual endometrial biopsies starting at age 35. Endometrial biopsies can be done in your doctor's office. They are often the first step a doctor takes when a post-menopausal patient has vaginal bleeding. However, only women with a very high risk for getting endometrial cancer, (like patients with a genetic syndrome), should be screened in this manner. Talk to your doctor about your endometrial cancer risk, and whether or not you need to be screened.

What are the signs of endometrial cancer?

Luckily, the early stages of endometrial cancer can cause symptoms. When a post-menopausal woman has vaginal bleeding, the first thing that needs to be looked into is the possibility of endometrial cancer. However, some of the other symptoms are occasionally non-specific, and don't always point toward a diagnosis of endometrial cancer.

As a tumor grows in size, it can produce a variety of problems including:

• vaginal bleeding (in a post-menopausal woman)
• abnormal bleeding (including bleeding in between periods, or heavier/longer lasting menstrual bleeding)
• abnormal vaginal discharge (may be foul smelling)
• pelvic or back pain
• pain on urination
• pain on sexual intercourse
• blood in the stool or urine

All of these symptoms are non-specific, and could represent a variety of different conditions; however, your doctor needs to see you if you develop any of these problems.

How is endometrial cancer diagnosed and staged?

When a post-menopausal woman has new onset vaginal bleeding, or any woman has symptoms that suggest a possibility of endometrial cancer, their doctors will want to get a sample of their endometrium called an endometrial biopsy. A biopsy is the only way to know for sure if you have cancer, because it allows your doctors to get cells that can be examined under a microscope. Once the tissue is removed, a doctor known as a pathologist will review the specimen. The pathologist can tell if it is cancer or not; and if it is cancerous, then the pathologist will characterize it by what type of tissue it arose from and what subtype of cancer it is, how abnormal it looks (known as the grade), and whether or not it is invading surrounding tissues.

The least invasive method to get a biopsy is to do it in your doctor's office. A thin flexible tube is passed through a woman's vagina and cervix and then into her uterus. A small amount of endometrium is removed; this can be somewhat uncomfortable and sometimes anti-inflammatory medications can help with the pain. Occasionally, your doctor will not be able to get enough endometrial tissue with an office biopsy. In this case, you will need to have a dilation and curettage (D & C). D&Cs are done in the hospital, in the operating room under anesthesia. Your doctor dilates the opening to your uterus and then scrapes and samples some endometrial tissue. This is often done with the aide of a thin scope, so your doctors can see what the inside of your uterus looks like.

Another technique that can help make the diagnosis of endometrial cancer is called transvaginal ultrasound. Ultrasound is an imaging modality that uses sound waves that bounce off of tissues and provide a picture of whatever is being investigated. By inserting an ultrasound probe into a woman's vagina, doctors can get a pretty good look at the thickness of her endometrium. If it appears too thick, then biopsies can be taken.

Endometrial cancer is a type of cancer that needs to be staged during a surgery; it is usually staged and treated during the same operation. In order to guide treatment and offer some insight into prognosis, endometrial cancer is staged into four different groups at the time of the surgery. Surgeons who specialize in gynecologic malignancies go through a careful inspection and sampling of a woman's pelvis during this procedure, and biopsy specimens are sent to a pathologist while the surgeon is still working. The staging system used for endometrial cancer is the FIGO system (International Federation of Gynecologists and Obstetricians).

The staging system is somewhat complex, but here is a simplified version of it:

Stage I - endometrial cancer confined to the body of the uterus (no cervical spread)
Stage II - endometrial cancer which has spread to the cervix (but not outside the uterus)
Stage III - endometrial cancer outside the uterus, but confined to the pelvis (but not in the bladder or rectum), cancer may have spread to pelvic lymph nodes
Stage IV - endometrial cancer which has spread to the bladder or rectum, or has distant metastasis (spread) to other organs

Generally, the higher the stage, the more serious the cancer is. Although surgery is required for staging, your physicians may want to order some other tests to better characterize the mass/masses and look for distant spread. Tests like CT scans (a 3-D x-ray) or MRIs (like a CT scan but done with magnets) can examine the pelvis and localized lymph nodes. You may get also get a colonoscopy, which uses a lighted scope to examine your rectum and colon, or a barium enema in which dye is inserted into your rectum and an x-ray is taken. These tests are to look for spread of the tumor to your colon and rectum. Your doctor may order a blood test called a CA-125, which if positive, predicts that there is spread of the cancer outside of your uterus. Each patient is an individual so the specific tests people get will vary; but overall, your doctors want to know as much about your particular tumor as possible so that they can plan the best available treatments.

What are the treatments for endometrial cancer?

Surgery

Almost all women with endometrial cancer will have some type of surgery in the course of their treatment. The purpose of surgery is first to stage the cancer, and then to remove as much of the cancer as possible. In early stage cancers (stage I and II), surgeons can often remove all of the visible cancer. Generally, women with endometrial cancer will have a hysterectomy (removal of the uterus) and bilateral salpingo-ooporectomy (removal of both ovaries and fallopian tubes) as part of their operation. This is because there is always a risk of microscopic disease in both of the ovaries and the uterus. The only circumstance in which a woman may not have an operation is if she has a very early stage cancer (IA) that looks favorable under the microscope (grade 1).

If a woman's tumor has these characteristics and she desires to maintain the ability to have children, then she can be treated by other modalities. Then after she is done having children, she will need to have her uterus, tubes and ovaries removed. With any other stage or grade of tumor, or in patients finished with childbearing, the entire operation should be performed in order to provide the best possible chance for a cure. Depending on the particulars of your case, your surgeon may also remove pelvic lymph nodes during the operation to look for possible cancer spread.

Women who have more advanced disease (stage III or IV) will often have debulking surgeries, which means that their surgeon will attempt to remove as much disease as possible. Data collected in many studies has demonstrated that the more tumor that it debulked, the better the long term outcome for the patient. Operations for endometrial cancer should be performed by surgeons who are trained in dealing with gynecologic malignancies because there are special skills and techniques necessary to deal with these tumors. In patients with very advanced cancers, surgery may be used for palliation- meaning that patients are operated on with the intent of easing their pain or symptoms, rather than trying to cure their disease. Talk to your surgeons about exactly type of operation you are going to undergo.

Radiotherapy

Endometrial cancer commonly receives Radiation therapy radiation therapy as well as surgery, and radiation has proven very effective in management. Radiation therapy uses high energy rays (similar to x-rays) to kill cancer cells. Radiation is usually offered after an operation as an adjuvant therapy to the surgery. Radiation is used in all but the most favorable cases (very early stages with low grades, and little invasion). Radiation is used to decrease the chances that the cancer will come back. Radiation can also be used in place of surgery in patients who are too ill to risk having anesthesia, but the best results come from the combination of both surgery and radiation.

Radiation therapy for endometrial cancer either comes from an external source (external beam radiation) or an internal source (brachytherapy). External beam radiation therapy requires patients to come in 5 days a week for up 6-8 weeks to a radiation therapy treatment center. The treatment takes just a few minutes, and is painless. Usually, patients will also be offered internal brachytherapy. Brachytherapy (also called intracavitary irradiation) allows your radiation oncologist to "boost" the radiation dose to the tumor bed. This provides an added impact while sparing your normal tissues.

This is done by inserting a hollow tube into your vagina. Then a small radioactive source is placed in the tube. A computer has calculated how long the source needs to be there, but usually for what is called low dose rate (LDR) brachytherapy, you will need to have the source in for a few days. This procedure is done in the hospital, because for those few days you have to remain in bed. Another type of brachytherapy, called high dose rate (HDR) brachytherapy, uses more powerful sources that only stay in for a few minutes. Although this option usually sounds better to patients, not all institutions offer it. Talk to your radiation oncologist about your options and their opinion as to HDR versus LDR for endometrial cancer treatment in your case.

Chemotherapy

Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. Chemotherapy is not as important as surgery and radiation for treating endometrial cancer. It is usually only used in endometrial cancers that are very advanced or recur after definitive treatment with surgery and radiation. There are many different chemotherapy drugs, and they are often given in combinations. Patients will usually have to go to a clinic to get the chemotherapy because many of the drugs have to be given through a vein.

Different chemotherapy regimens are used for different purposes. Some of the drugs used in endometrial cancer chemotherapy include: Cisplatin, Carboplatin, Doxorubicin, and Paclitaxel. There are advantages and disadvantages to each of the different regimens that your medical oncologist can discuss with you. Based on your own health, your personal values and wishes, and side effects you may wish to avoid, you can work with your doctors to come up with the best regimen for your cancer and your lifestyle.

Hormonal Therapy

When the pathologist examines your tumor specimen, he or she finds out if the tumor is expressing estrogen and progesterone receptors. Patients whose tumors express progesterone receptors are candidates for therapy with progesterone like agents such as hydroxyprogesterone and medroxyprogesterone. These medications are usually used in patients with very advanced or recurrent endometrial cancers when they are not healthy enough to undergo surgery or radiation.

Follow-up testing

Once a patient has been treated for endometrial cancer, they need to be closely followed for a recurrence. At first, you will have follow-up visits fairly often. The highest chance for a recurrence is in the first 3 years after diagnosis. The longer you are free of disease, the less often you will have to go for checkups. Your doctor will tell you when he or she wants follow-up visits, pelvic ultrasounds, CA-125 levels and/or CT scans depending on your case. Your doctors will also perform pelvic examinations during each of your office visits During these pelvic exams, your doctors may get samples of your vaginal cells to look for recurrent cancer.

They may do this a few times a year for the first couple years. It is very important that you let your doctor know about any symptoms you are experiencing and that you keep all of your follow-up appointments.

Clinical trials are extremely important in furthering our knowledge of this disease. It is though clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your doctor about participating in clinical trials in your area.

This article is meant to give you a better understanding of endometrial cancer. Use this knowledge when meeting with your physician, making treatment decisions, and continuing your search for information.

References

The American Cancer Society All About Endometrial Cancer Detailed Guide www.cancer.org
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Jemal, A. et. al (2002). Cancer Statistics, 2002. Ca: a Cancer Journal for Clinicians 52 (1):23-47
National Cancer Institute. What You Need To Know About Endometrial Cancer.www.cancer.gov
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