If you’ve been diagnosed with advanced endometrial cancer, it’s a good idea to learn as much as you can about the condition. You’ll better understand your doctor’s recommendations and explanations and know what questions you should ask at appointments.
What Is Advanced Endometrial Cancer?
Endometrial cancer is cancer of the endometrium, which is the inner lining of the uterus. This type of cancer is considered advanced when it has spread, or “advanced,” beyond the uterus and the cervix. This includes stage III and IV cancers.
The places in the body affected by cancer outside the uterus are often referred to as “extrauterine sites.” The severity of the cancer depends, in part, on how many extrauterine sites are involved and how far they are from the uterus. Advanced endometrial cancers may involve only nearby tissue, such as the fallopian tubes or ovaries, or they may have spread, or “metastasized,” to more distant organs, such as the lungs.
What Causes Advanced Endometrial Cancer?
It’s not known what exactly causes endometrial cancer. It’s believed that it has a lot to do with the female sex hormones estrogen and progesterone. Endometrial cancer cells have hormone receptors for estrogen and progesterone on their surface.
Hormone receptors are proteins on the surface of cells that latch onto the corresponding hormone in order to trigger a certain reaction. Given that endometrial cancer cells have these hormone receptors, and hormone imbalances are often involved in endometrial cancer, experts believe estrogen and progesterone play a big part in the development of this type of cancer. Some risk factors for endometrial cancer, such as certain medications or health conditions, may cause hormone imbalances that lead to the cancer.
Research also shows that certain genes that usually help prevent cancer can sometimes have defects that lead to the development of endometrial and other cancers. These defective genes can run in families, which makes some cancers hereditary.
Defective genes can tell the cells in your uterus to multiply more quickly than normal and cause an overgrowth of tissue there. Cancer-promoting gene defects could also tell abnormal cells in your uterus to go on living when healthy cells would have died off. All this leads to extra cells in the uterus that can form tumors and become cancerous.
Cancer in the uterus usually causes symptoms like abnormal bleeding, which would lead to catching the cancer before it advances. But if it’s not caught in time, tumors can grow larger and reach into other parts of the reproductive system. Cancer cells in the uterus can also break off and spread to other parts of the body, which leads to advanced endometrial cancer.
What are the risk factors for endometrial cancer?
A number of factors can put you at increased risk for endometrial cancer.
Greater lifetime exposure to estrogen
There are several reasons you could have higher levels of estrogen in your body, such as:
- Using estrogen-only hormone replacement therapy to relieve symptoms of perimenopause and menopause
- Taking tamoxifen to treat breast cancer or keep it from coming back
- Getting your first period at a younger age
- Entering menopause at a later age
- Never being pregnant
- Obesity, as fat cells secrete androgen, which can convert to estrogen
Certain gynecologic conditions
These conditions may raise your risk for endometrial cancer. Talk to your doctor about your increased risk and how to manage it if you have one of these:
- Polycystic ovary syndrome (PCOS)
- Estrogen-secreting ovarian tumors
- Endometrial hyperplasia
Metabolic syndrome
This group of health conditions – which usually includes obesity, diabetes, and high blood pressure – raises risk for endometrial cancer.
Age
Your risk increases with age, especially after menopause.
Genetic conditions
Some people are born with certain gene variants that raise their risk for one type of cancer or a group of cancers. These are known as hereditary cancer syndromes. Both Lynch syndrome and Cowden syndrome are examples of hereditary syndromes that cause an increased risk for endometrial cancer.
Family history
Even without a hereditary syndrome, if you have a first-degree relative (for instance, your mother, sister, or daughter) who has had endometrial cancer, you’re at greater risk.
Race
Women of any race face equal risk of developing endometrial cancer, but Black women are more likely to have advanced disease and to die from it. Both Black and Hispanic women are more likely to have aggressive tumors compared to women of other racial and ethnic backgrounds.
Chemical exposure
Long-term use of hair straightening products, also called hair relaxers, most often used by Black women, has been linked to increased risk for endometrial cancer. Researchers don’t know specifically which ingredient in these products causes the health risk.
Radiation aimed at your pelvis or lower abdomen to treat another cancer can raise risk for endometrial cancer later.
Racial Disparities in Endometrial Cancer
In the U.S., simply being Black raises risk for advanced endometrial cancer. While both Black and White women face the same lifetime risk – about a 3% chance – of getting endometrial cancer, Black women with endometrial cancer are more likely to have advanced disease and to die from it.
This disparity is due in part to differences in access to health care. By the time they get a diagnosis, the cancer has often already become advanced in Black women.
Even after diagnosis, research shows, Black women don’t typically receive the same level of care as White women. They are less likely than White women to have surgery for endometrial cancer, and they may be more likely to stop going for treatment because of bad experiences with the health care system.
But lack of access to care alone does not explain the significant differences in endometrial cancer outcomes between Black women and other women.
Studies show that Black women with endometrial cancer are more likely than White, Asian, or Hispanic women to have one of the more aggressive type II forms of the condition. These subtypes are more likely to become advanced cancers than type I. Black women also tend to have higher grade cancers – the ones more likely to grow fast and spread – at diagnosis than White women.
How Does Advanced Endometrial Cancer Affect the Body?
At first, endometrial cancer only affects the uterus, so the main symptom is vaginal bleeding. Before menopause, that means bleeding or spotting between periods or periods that are longer or heavier than usual. After menopause, any bleeding would be considered abnormal.
You might also have:
- Unusual vaginal discharge
- Pelvic pain or pressure
- Pain during sex
- Pain during urination
When the cancer advances, you might have some of these symptoms:
- Weight loss for no reason
- Leg or back pain
- Tiredness
- Loss of appetite
If the cancer spreads to distant organs, your other symptoms would depend on which organs are affected. The lungs, liver, and bones are among the most common distant sites that endometrial cancer reaches. When it spreads to these places, you might have:
- Coughing, chest pain, shortness of breath if the cancer spreads to the lungs
- Yellowing of the skin or whites of the eyes or itchy skin if the cancer spreads to the liver
- Bone pain or fractures if the cancer spreads to the bones
Endometrial Cancer Types, Grades, and Genetic Profiles
Doctors divide endometrial cancers into two types: the less aggressive type I and the faster progressing type II. Then they further subdivide the types based on what the cancer cells look like under the microscope.
Type I
Endometrioid adenocarcinoma, the most common type of endometrial cancer, is a type I cancer. This form of uterine cancer is usually connected with estrogen exposure. It’s less aggressive and has a generally good outlook.
Type II
This type includes several rare subtypes of endometrial cancer, such as:
- Serous carcinoma
- Clear cell carcinoma
- Carcinosarcoma
- Undifferentiated/dedifferentiated carcinoma
These less common types of endometrial cancer tend to grow more quickly than type I disease and are more likely to spread to tissue outside of the uterus.
Endometrial cancer grades
Cancer grades are based on how different the cancer cells look from normal cells. The more they differ from normal cells, the more likely they are to grow and spread quickly.
Grade I
These cancer cells – also called low-grade or well differentiated – look very similar to normal cells. They usually grow slowly and are not as likely to spread as higher grade cells.
Grade II
Also called moderately differentiated or moderate grade, these look more abnormal than grade I cells. They come with greater risk of growing quickly and advancing.
Grade III
The cells – also described as high grade or poorly differentiated – look very abnormal compared to normal, healthy cells. They are the most likely to grow fast and advance outside the lining of the uterus.
Endometrial cancer by gene type
Cancer cells contain genes just like your normal healthy cells do. Sometimes endometrial cancer cells have variations in certain genes that help them multiply and spread. Your doctor might order tests to see if your cancer cells have any of these gene changes. This information can sometimes help guide doctors toward the best treatment for you.
The gene changes are put into what are called molecular classifications in these groups:
- MMRd
- NSMP
- p53abn
- POLE mutations
How to Prevent Advanced Endometrial Cancer
There’s no surefire way to prevent endometrial cancer, but there are some things that may lower your risk, including:
- Long-term use of birth control pills
- An intrauterine device (IUD)
- Hormone replacement therapy after menopause that contains both estrogen and progesterone
- Pregnancy
- Getting treatment for endometrial hyperplasia if you have it
- Regular exercise
- Maintaining a healthy weight
- Following additional recommendations for cancer prevention if you have Lynch syndrome
The way to keep endometrial cancer from advancing is to catch it early before it spreads. The best way to do this is to see your doctor if you ever have abnormal vaginal bleeding.
What’s the Outlook for People With Advanced Endometrial Cancer?
The term “advanced endometrial cancer” refers to any cases in which the cancer has advanced beyond the uterus and the cervix. That includes a wide range of situations that may lead to very different outlooks. Someone whose cancer has only reached the nearby lymph nodes may have a better prognosis than someone whose cancer has metastasized to their bones or brain. Also, cancers that have advanced to only one site beyond the uterus tend to have a better prognosis than those that have spread to multiple sites.
Survival statistics for advanced endometrial cancer include all of these diverse cases, which helps explain the wide range in these numbers:
- 20%-60% of people diagnosed with stage III and stage IV endometrial cancer are alive five years later.
- 13%-65% of people survive five years after a recurrence of endometrial cancer.
But the outlook may be improving. The FDA recently approved two existing immunotherapy drugs, dostarlimab (Jemperli) and pembrolizumab (Keytruda), to be used in combination with chemotherapy for the treatment of advanced endometrial cancer or cancer that has come back. Those drugs extended overall survival and progression-free survival in clinical trials.
Other medications may be on the way. Several clinical trials to test new treatments for advanced endometrial cancer are currently recruiting and in progress at hospitals around the country and around the world. If you are facing a diagnosis of advanced endometrial cancer, it never hurts to ask your doctor whether you might be a good fit for a clinical trial.
Show Sources
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SOURCES:
American College of Radiology: “ACR Appropriateness Criteria: Advanced Stage Endometrial Cancer.”
American Cancer Society: “What Causes Endometrial Cancer?” “Endometrial Cancer Risk Factors,” “Lung metastases.”
Mayo Clinic: “Endometrial Cancer.”
Fred Hutch Cancer Center: “Racial disparities in endometrial cancer: Improving diagnosis and treatment.”
Cancer Causes & Control: “Racial and ethnic differences in tumor characteristics among endometrial cancer patients in an equal-access healthcare population.”
American Journal of Public Health: “Endometrial Cancer: Socioeconomic Status and Racial/Ethnic Differences in Stage at Diagnosis, Treatment, and Survival.”
American College of Obstetricians and Gynecologists: “Endometrial Cancer Frequently Asked Questions.”
Moffitt Cancer Center: “Endometrial (Uterine) Cancer Symptoms.”
National Health Service (UK): “Womb (uterus) cancer.”
Journal of Clinical Oncology: “Patterns of distant metastases in patients with endometrial carcinoma: A SEER population-based analysis.”
Cancer Society (NZ): “Cancer that has spread to the liver.”
Cleveland Clinic: “Bone metastasis.”
Johns Hopkins Medicine: “Endometrial Cancer.”
Cancer Research UK: “Types and grades of womb cancer.”
Gynecologic Oncology: “Real-world outcomes in patients with advanced endometrial cancer: A retrospective cohort study of US electronic health records.”
FDA: “FDA approves pembrolizumab with chemotherapy for primary advanced or recurrent endometrial carcinoma,” “FDA expands endometrial cancer indication for dostarlimab-gxly with chemotherapy.”
