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Advances in Endometrial Cancer Research

Researchers are testing certain targeted therapies for some types of endometrial cancer.

Credit: iStock

NCI-funded researchers are working to advance our understanding of how to prevent, detect, and treat uterine cancer, which includes endometrial cancer and uterine sarcoma. Endometrial cancer is the fourth most common cancer in women in the United States, and incidence has been rising in recent years, particularly among non-Hispanic black women. Uterine sarcoma is much less common and often more aggressive and harder to treat.

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.

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.

Immunotherapy

Immunotherapy treatments help the immune system to better fight cancer. Immune checkpoint inhibitors have shown promise in treating advanced endometrial cancer, especially tumors that 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 syndromeassociated endometrial cancers, as well as in up to 35% of endometrial cancers that are not associated with Lynch syndrome.

Other advances include:

Radiation Therapy

Adjuvant radiation: Researchers are looking at whether women with dMMR would benefit from adjuvant radiation. As more is learned from studies, the goal is to make it easier to predict which patients will benefit from receiving radiation after their primary treatment.

Targeted Therapy

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. The targeted therapy lenvatinib is used with pembrolizumab to treat some women with advanced endometrial cancer. A definitive NCI phase 3 study is comparing the combination of pembrolizumab and lenvatinib with chemotherapy in patients with stage III, IV, or recurrent endometrial carcinoma.

Several more 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 will be reopening soon to test three additional combinations of targeted therapies.

  • The NCI-MATCH Trial explores how well treatment directed by tumor genetic testing works in patients with certain cancers, including endometrial, that has progressed after at least one line of standard treatment or for which no standard treatment approach exists. The goal is to determine whether treating cancer based on these genetic changes is effective, regardless of cancer type.

Treatment Combinations

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.

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.

NCI-Supported Research Programs

See a full list of uterine cancer research projects that NCI funded in FY 2018.

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.

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:

View the full list of Uterine Cancer Research Results and Study Updates.

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