Understanding Endometrial Cancer

Symptoms, Causes, Diagnosis, and Treatments

diagram of uterus surrounded by cancer cells
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Endometrial cancer is a cancer that affects the lining of the uterus and is most common in women after menopause. Of concern is that this type of cancer has been increasing in North America and Europe. What should you know about the symptoms, diagnosis, and treatments for this cancer?

Endometrial Cancer—Definition

Endometrial cancer, also known as uterine cancer, is a cancer that develops in the cells lining the uterus (the endometrium) and is the most common type of cancer to affect the body of the uterus.

The endometrium is very active in a woman’s menstrual cycle and pregnancy. During the first half of the menstrual cycle, estrogen causes the endometrium to build up in preparation for implantation of the pregnancy. If pregnancy does not occur, progesterone leads to the breakdown of this tissue, which is then shed during a woman’s monthly period.

Another less common cancer of the uterus, uterine sarcoma, begins in the layer of tissue beneath the endometrium called the myometrium (the muscle of the uterus).

There are a number of subtypes of endometrial cancer, such as adenocarcinoma, adenosquamous, carcinoma, clear cell carcinoma, and others. Most of these cancers are diagnosed early, at a stage when surgery offers a good chance for a cure. That said, the risk factors which raise the risk of developing these cancers have increased as have the number of diagnoses each year in developed countries.

Endometrial vs. Cervical Cancer

The difference between endometrial cancer and cervical cancer can be confusing since the cervix is actually the lower part of the uterus. While the same organ is affected, there are many important differences which range from screening to the most important causes of these cancers.

The upper part of the uterus includes the body or fundus, whereas the cervix is the lower part of the uterus, which attaches to the vagina.

Incidence of Endometrial Cancer

Endometrial cancer has been estimated to affect 61,380 women in 2017, resulting in the death of 10,920 of these women. It's been found that endometrial cancer is increasing in recent years, especially in North America and Europe. It's thought that this is likely related to the increase in risk factors in recent years, such as obesity, women having fewer children, and delayed childbirth. While endometrial cancer was once less common in African American women than whites in the United States, the incidence is now similar.

Signs and Symptoms

Early on, a woman may not have any symptoms with endometrial cancer. When symptoms develop, the most common is a change in uterine bleeding. This could be bleeding after a woman has gone through menopause and no longer has periods. In premenopausal bleeding, endometrial cancer may result in abnormal uterine bleeding, such as bleeding and spotting between periods. Some women do not have distinct bleeding but instead notice a clear or slightly blood-tinged vaginal drainage. Some women may develop anemia (a low red blood cell count) as a result of bleeding.

Other possible symptoms include pelvic pain or a pelvic mass. When the cancer is advanced, symptoms such as unintentional weight loss, fatigue, or bowel and bladder changes may be noted.

Causes and Risk Factors

While we aren’t certain about the exact causes of endometrial cancer, several risk factors have been identified. Known and possible risk factors include:

  • Age: Endometrial cancer is more common in women beyond the age of menopause.
  • Elevated estrogen levels (without an accompanying elevation in progesterone): Any condition that increases estrogen levels without a similar increase in progesterone may increase the risk.
  • Oral contraceptive use: Use of oral contraceptives for at least one year reduces the risk. The reduction in risk is greatest for women who use birth control pills for an extended period of time and continues to reduce the risk for several years after the pills are discontinued.
  • Hormone replacement therapy (HRT): HRT with estrogen but without progesterone (unopposed estrogen therapy) increases the risk of endometrial cancer.
  • Reproductive factors: Women with longer reproductive years, such as those who begin menstruating early or those who go through menopause late are at greater risk. Women who do not have children are at a greater risk than those who have children.
  • A history of infertility
  • A history of endometrial hyperplasia
  • Obesity: Being obese triples the risk of developing the disease.
  • Polycystic ovarian syndrome (PCOS): PCOS increases the risk of developing endometrial cancer although some of the treatments for PCOS, such as metformin, may reduce the risk.
  • Diabetes: Endometrial cancer risk is four times higher in women with diabetes.
  • IUD use: Having used an IUD lowers a woman’s risk of endometrial cancer.
  • Tamoxifen: The use of tamoxifen to reduce the risk of recurrence or lower the risk of developing breast cancer can increase the risk of developing endometrial cancer.
  • Certain ovarian tumors such as a granulosa cell tumor secrete estrogen and can raise the risk of endometrial cancer.
  • A history of having cancers such as breast cancer or ovarian cancer
  • Having a family history of endometrial cancer or colon cancer
  • People with hereditary cancer syndromes such as Lynch syndrome (hereditary nonpolyposis colorectal cancer or HNPCC)
  • A history of radiation to the pelvis as part of cancer treatment
  • Having a sedentary lifestyle
  • Eating a high-fat diet

Screening/Early Detection

Unlike cervical cancer, there is not a routine test for screening for endometrial cancer. Women who are at an increased risk for developing the disease, such as those who have a family history, a hereditary cancer syndrome such as Lynch syndrome, or who have been using tamoxifen to treat or reduce the risk of breast cancer should talk to their doctor about screening. For some women, tests such as an endometrial biopsy and/or uterine ultrasound may be considered to increase the chance of detecting the disease as early as possible.

Diagnosis of Endometrial Cancer

The diagnosis may be suspected from a Pap smear, but Pap smears are not an effective screening tool for the disease. Diagnosis usually begins with a pelvic exam, although early cancers are not usually palpable.

If you have had abnormal vaginal bleeding there are several tests which your doctor may consider. A transvaginal ultrasound (an ultrasound performed by inserting the ultrasound probe into your vagina) can be done to look at the thickness of your endometrium. A saline solution may also be infused into your uterus (sonohysterogram) before the procedure to improve visualization of any abnormalities.

A hysteroscopy is a procedure in which a "telescope" is inserted through your cervix into your uterus to visualize the uterine lining.

A common study is an endometrial biopsy. In this office procedure, a tool is inserted through your vagina to get a scraping of the inside of your uterus to evaluate in the lab. Your doctor may also recommend a dilation and curettage (D and C) which is often done in the operating room under a general anesthetic. With anesthesia and dilation of your cervix, a better sample of your uterine lining may be obtained.

If endometrial cancer is suspected, a biopsy is needed to confirm the diagnosis as well as further define the characteristics of the tumor.

Staging

To determine the best treatment options, accurate staging is a critical step after your diagnosis. Staging is done by looking at the size of the tumor, it's aggressiveness based on its appearance under the microscope (tumor grades from 1 to 3), and testing to see if the cancer has invaded or spread to any tissues outside of the uterus.

Similar to other cancers, these tumors are often given a "TNM" rating in which T stands for the size of the tumor (and sometimes other characteristics), N stands for the involvement of nearby or distant lymph nodes, and M represents metastases, or spread to distant organs.

If there is a chance that the cancer has invaded or spread to other organs, other tests may include a cystoscopy and/or proctoscopy to look for any evidence of spread to the bladder or rectum, and a CT, MRI, and/or PET scan to look for distant spread of the tumor.

Like many other solid tumors, endometrial cancer is broken down into 4 stages (as of January 2018 there is no longer a stage 0). These include:

  • Stage 1: The cancer is limited to the uterus, and has not spread to the cervix, other areas of the pelvis, or distant organs.
  • Stage 2: The tumor has spread to the cervix, but not to other parts of the body.
  • Stage 3: The tumor has spread beyond the uterus, but all areas of spread are still in the pelvic region.
  • Stage 4: The cancer has spread to the bladder, rectum, or distant areas of the body.

These stages are further broken down into substages (such as stage 2A and 2B) depending on other characteristics of the tumor.

Treatment Options for Endometrial Cancer

The best treatment options for endometrial cancer depend on the stage of the disease, the symptoms, as well as other factors such as general health. Options include:

Surgery: Surgery is the most common method of treating endometrial cancer. In this surgery the uterus is removed (hysterectomy), most often along with the tubes and ovaries (salpingo-ophorectomy). For women who have completed childbearing, this does not usually present much of a problem other than the risk of surgery. For those who are younger and had wished to have a child or more children, however, this can be heart-wrenching.

Radiation therapy: Radiation therapy is a local treatment which can be used if there is a possibility some cancer cells have spread beyond the region removed with surgery.

Hormone therapy: Hormone therapy may be used to reduce the amount of estrogen or increase the amount of progesterone in the body. The most common treatments include one of the types of progesterone. For tumors that are a higher stage or have recurred, other possible treatments include tamoxifen, luteinizing releasing hormone agonists, and aromatase inhibitors.

Chemotherapy: Chemotherapy is not usually needed for early-stage endometrial cancers. For cancers that have spread or recurred, however, chemotherapy is often used.

Clinical trials: All of the treatments for endometrial cancer that are now available were once studied in clinical trials. There are ongoing clinical trials for endometrial cancer looking for ways to both improve survival and reduce the side effects and invasiveness of treatments.

Coping

Receiving a diagnosis of cancer no matter the type or stage is frightening. Education is empowering, and learning about your cancer can help you be your own advocate in your care. Take a moment to learn about how to find good cancer information online. Support is also essential. A diagnosis of cancer is a good time to gather your support system around you. Many people find it helpful to join a support group in their community or take part in one of the online support groups or support communities for endometrial cancer.

Prognosis

The overall prognosis for endometrial cancer in the United States is good, as many of these cancers are found early. Some uncommon types of endometrial cancer such as clear cell carcinoma are more aggressive and have a poorer prognosis.

Current 5-year survival rates are 75-88 percent for stage I disease, 69 percent for stage II, 47-58 percent for stage III, and 15-17 percent for stage IV. It's important to note that statistics are often several years old and do not reflect newer and more effective treatments that have been approved since that time.

A Word From Verywell

Endometrial cancer is a cancer of the uterus which is unfortunately increasing in the United States and Europe. The most common symptom (for around 90 percent of women) is abnormal uterine bleeding. Fortunately many women seek treatment if they have abnormal periods or bleed after menopause, and many of these tumors are diagnosed in the earlier stages. The best treatment depends on the stage of diagnosis.

If you've been diagnosed with endometrial cancer the most important thing you can do is become your own advocate in your care. Ask a lot of questions. Consider getting a second opinion. And learn about your disease.

Sources:

Lortet-Tiuelent, J., Ferlay, J., Bray, F. et al. International Patterns and Trends in Endometrial Cancer Incidence, 1978-2013. Journal of the National Cancer Institute. 16 October 2017.

National Cancer Institute. Endometrial Cancer Treatment (PDQ)—Health Professional Version. Updated 08/18/17. https://www.cancer.gov/types/uterine/hp/endometrial-treatment-pdq

Tang, Y., Zhu, L., Li, Y. et al. Metformin Use is Associated with Reduced Incidence and Improved Survival of Endometrial Cancer: A Meta-Analysis. BioMed Research International. 2017. 2017:5905384.