Advances in Endometrial Cancer Research
NCI-funded researchers are working to advance our understanding of how to prevent, detect, and treat endometrial cancer, which is a type of uterine cancer. The other type, uterine sarcoma, is much less common and can be more aggressive and harder to treat.
There are two main subtypes of endometrial cancers: endometrioid and non-endometrioid. Both occur in the inner lining of the uterus, but they look different under a microscope.
- Endometrioid tumors are more common (they make up 75% to 80% of uterine cancers), are typically diagnosed at an early stage, and may have a favorable prognosis.
- Non-endometrioid tumors (including serous, clear cell, and other, rarer types of endometrial cancer) are often more aggressive and have a poor prognosis.
This page highlights some of the latest research in endometrial cancer, NCI-supported programs that are fueling progress, and research findings from recent studies.
Early Detection of Endometrial Cancer
There is no standard screening test for endometrial cancer. Researchers are exploring a variety of ways to detect endometrial cancer before symptoms develop. This includes studying genetic risk factors that increase the risk of endometrial and other cancers.
Abnormal bleeding: Early-stage endometrial cancer and even atypical hyperplasia of the endometrium (which is not cancer but can become cancer) can cause vaginal bleeding in postmenopausal women. Although bleeding can have many causes, research shows that most postmenopausal women with endometrial cancer had abnormal vaginal bleeding before diagnosis. This confirms the value of follow-up testing in women who have this symptom.
New biomarkers: Scientists are looking at potential biomarkers to further improve diagnosis of early endometrial cancer. A biomarker is a molecule found in blood or other tissues that is a sign of a condition or disease.
In the DETECT Study, for example, researchers from NCI’s Division of Cancer Epidemiology and Genetics (DCEG) are studying ways to detect endometrial cancer in samples of uterine tissue collected using tampons. By comparing uterine tissue from women who are having a hysterectomy for endometrial cancer, with tissue from women having a hysterectomy for an unrelated benign condition, scientists hope to find biomarkers that may eventually lead to noninvasive early detection approaches. This study is also designed to reach a racially diverse group of women.
Researchers funded by NCI’s Early Detection Research Network (EDRN), a network of institutions developing biomarkers to detect cancer in its early stages, designed a test called PapSEEK that analyzes cells from the lining of the uterus. In a research study, the test identified cancer-related DNA alterations in most women with known endometrial cancer, but also in a few women without the disease.
Next, researchers will see whether the test detects endometrial cancer in women who have not already been diagnosed with the disease. More studies of PapSEEK are needed before the test will be ready for use in patient care.
Familial genetic risk: Lynch syndrome is an inherited DNA repair disorder in which people have a higher-than-normal risk of developing certain cancers, including endometrial cancer, colon cancer, and, less frequently, ovarian cancer. About 3% of endometrial cancers are caused by Lynch syndrome. The Society for Gynecological Oncology recommends that all women diagnosed with endometrial cancer be tested for this disorder. This will aid in treatment decisions and also help with prevention and screening of other cancers in the patient and their blood relatives.
Advances in Endometrial Cancer Treatment
Surgery is the standard treatment for early-stage endometrial cancer. Additional treatment, depending on the stage of disease, may include radiation with or without chemotherapy, hormone therapy, immunotherapy, and some targeted therapies. Several new treatments for advanced disease have become available.
One area that is changing practice is determining the molecular subtypes of cancers and deciding treatment according to type. Researchers have found that there are different molecular subtypes of endometrial cancer. These subtypes differ in how likely it is that the cancer will come back after treatment.
Doctors are now using these subtypes to help choose the best treatments for certain patients with endometrial cancer. For some patients, getting a genetic analysis might be recommended. Going forward, use of molecular analysis of endometrial cancers will be used to guide treatment decisions. This includes intensifying treatment where needed, or reducing the intensity of treatment if it's shown to be safe and equally effective.
Immunotherapy treatments help the immune system to better fight cancer. One type, called an immune checkpoint inhibitor, has shown promise in treating subsets of advanced endometrial cancer. For example, some people have defects in a specific DNA repair process called mismatch repair. Mismatch repair deficiency (dMMR) can cause cells to develop high microsatellite instability (MSI-H), in which many mutations arise.
dMMR and MSI-H are seen in Lynch syndrome–associated endometrial cancers, as well as in up to 35% of endometrial cancers that are not associated with Lynch syndrome.
An NCI study is testing whether combining the drugs nivolumab and ipilimumab is better than nivolumab alone in shrinking tumors in patients with deficient mismatch repair system (dMMR) recurrent endometrial carcinoma who have already had a prior immune checkpoint inhibitor and had their disease progress. The combination of these two drugs has shown they can shrink or stabilize cancers with deficient mismatch repair system, although this has not been studied in endometrial cancer until now.
Other advances include:
- The immune checkpoint inhibitor pembrolizumab (Keytruda) has been approved for treating patients with advanced endometrial cancer that is dMMR or MSI-H, cannot be removed surgically, and has gotten worse after other treatments.
Pembrolizumab has also been approved to be used together with the targeted therapy lenvatinib (Lenvima) for some patients with advanced endometrial cancer that is not MSI-H or dMMR and has gotten worse after other treatments. A 2022 clinical trial showed that combining the two drugs led to longer progression-free survival and overall survival among patients than using chemotherapy.
- One NCI-sponsored trial is studying using chemotherapy with or without pembrolizumab for women with newly diagnosed advanced endometrial cancer.
In a different trial, researchers are examining the role of adding pembrolizumab to standard radiation therapy for early-stage endometrial cancer that is MSI-H or dMMR.
Targeted therapies are drugs or other substances that interfere with specific molecules, or targets, to block the growth and spread of cancer with less harm to normal cells.Several targeted therapies are being studied for treating advanced endometrial cancer. Some examples include:
- One NCI-sponsored trial is studying how well the drugs olaparib (Lynparza) and cediranib maleate (Recentin) work in treating patients with endometrial cancer that has come back, does not respond to treatment, or has spread elsewhere in the body. These drugs may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase 2 clinical trial is now testing three additional combinations of targeted therapies.
- A new trial will test the combination of olaparib with the chemotherapy drug temozolomide in people with a type of uterine sarcoma called leiomyosarcoma. The hope is that using both drugs together will work better to treat the disease than giving either drug alone.
- Another trial will test whether adding certain targeted therapies to chemotherapy will shrink tumors in patients with one of two rare types of endometrial cancer that have excess amounts of a protein called HER2 (also called HER2 positive cancer). The treatment will target the HER2 protein and will be given in a new form, a subcutaneous shot (under the skin), rather than patients having another IV infusion.
- The NCI-MATCH Trial is one of the first major clinical trials to match people who have cancer with treatment based on genetic changes in their tumor rather than their type of cancer. This trial has shown that targeting genetic changes in a tumor may be an effective way to treat cancer. It has also shown that people with advanced cancer may benefit from genomic sequencing to help plan their treatment. Information learned from NCI-MATCH is leading to new precision medicine trials, such as ComboMATCH, which will test combinations of drugs.
Radiation therapy and cisplatin: An NCI randomized phase 2 trial is comparing the combination of radiation therapy and cisplatin with radiation therapy alone in treating patients with endometrial cancer that has come back. The trial is now closed and researchers are analyzing the results.
Surgery and chemotherapy versus surgery and chemoradiation: An NCI-funded study found that, among women with locally advanced endometrial cancer, those who received radiation in addition to chemotherapy (chemoradiation) after surgery had the same rate of cancer recurrence as those who received chemotherapy without radiation. More research is needed to determine whether specific groups of patients would benefit from radiation.
Rising Endometrial Cancer Rates and Disparities
Unlike most other cancers in the United States, endometrial cancer has increased in both incidence and death rates in recent years. These changes reflect increases in aggressive (non-endometrioid) subtypes of uterine cancer, with endometrioid subtypes having remained fairly stable.
Recent studies have shown that these increases are seen in all racial and ethnic groups. However, a 2019 study from NCI showed that Black women have the highest incidence rates and a 2022 NCI study showed that they have higher death rates and the poorest survival.
The reasons for the increases in non-endometrioid subtypes and the disparities across groups are not clear, but NCI-funded studies are seeking to understand their origin. For example:
- In addition to studying biomarkers in tampon specimens, the aforementioned DETECT study has expanded their aims to investigate possible sources of these disparities, such as differences in risk factors, in molecular markers and in care delays.
- The Carolina Endometrial Cancer Study seeks to address this gap in a clinical trial that analyzes endometrial tumors to identify genetic details and guide treatment strategies. Women from across the state of North Carolina will be recruited, with a goal of half the participants being Black.
NCI-Supported Research Programs
Many NCI-funded researchers at the NIH campus, and across the United States and the world, are seeking ways to address uterine cancer more effectively. Some research is basic, exploring questions as diverse as the biological underpinnings of cancer and the social factors that affect cancer risk. And some is more clinical, seeking to translate this basic information into improving patient outcomes.
- The Endometrial Specialized Programs of Research Excellence (SPOREs) promotes collaborative translational cancer research. This group works to improve prevention and treatment approaches, along with molecular diagnostics, in the clinical setting to help patients with endometrial cancer.
- NCI”s Division of Cancer Prevention (DCP) is addressing rising endometrial cancer rates by supporting gynecologic cancer prevention research and developing concepts for future studies.
- Approaches to Identify and Care for Individuals with Inherited Cancer Syndromes seeks the best approaches to identify those with an inherited cancer syndrome and provide appropriate follow-up care.
- The NCI-funded Colon Cancer Family Registry has established an international cohort of thousands of colorectal cancer patients, their relatives, and other individuals at increased risk of colorectal and other cancers, including endometrial cancer. More than 10,000 families from the United States, Canada, Australia, and New Zealand have been registered. The database includes more than 2,000 individuals with Lynch syndrome from 781 families.
- The Epidemiology of Endometrial Cancer Consortium (E2C2) is an NCI-supported consortium studying the causes and origins of this cancer through collaboration among investigators. The goal of E2C2 is to combine data across studies to better understand endometrial cancer.
Clinical Trials for Uterine Cancer
NCI funds and oversees both early- and late-phase clinical trials to develop new treatments and improve patient care. Trials are available for the treatment of both endometrial cancer and uterine sarcoma.
Endometrial Cancer Research Results
The following are some of our latest news articles on endometrial cancer research:
- Immunotherapy’s Role in Treating Endometrial Cancer Expected to Grow
- Trastuzumab May Improve Survival in Women with Rare Endometrial Cancer
- Women Experience More Side Effects from Pelvic Radiation than Realized
- Can Some Women Treated for Endometrial Cancer Forgo Radiation after Surgery?
- Study Shows Incidence Rates of Aggressive Subtypes of Uterine Cancer Rising
- Study Provides Closer Look at Postmenopausal Bleeding and Endometrial Cancer
View the full list of Uterine Cancer Research Results and Study Updates.