Large Genomic Study Identifies Endometrial Cancer Subtypes, Treatment Opportunities

Endometrial tumors can be reclassified into distinct subtypes based partly on their genomic makeup and may respond to targeted drugs already being tested in clinical trials, according to a large-scale genomic analysis led by researchers at Memorial Sloan-Kettering Cancer Center and other centers within The Cancer Genome Atlas (TCGA) Research Network.

Published in the May 2 issue of the journal Nature, the findings may help doctors more accurately diagnose endometrial cancer and choose treatments that will target genomic mutations in women with endometrioid and uterine serous adenocarcinomas, the two most common types of endometrial cancer. The findings could also guide clinical trials and the development of new drugs.

“These findings have an immediate therapeutic application, as patients with endometrial cancer can be tested routinely to see whether they qualify for a targeted therapy clinical trial,” said Memorial Sloan-Kettering gynecologic oncologist Douglas A. Levine, MD, corresponding author on the study, principal investigator of Memorial Sloan-Kettering’s TCGA Tissue Source Site, and Co-Chair of TCGA’s Endometrial Working Group. “The current landscape of treatment for endometrial cancer is quite chaotic, and this research may provide order to that landscape, especially for more-aggressive endometrial cancers.”

Endometrial cancer, which forms in the tissues lining the uterus, is the fourth leading type of cancer among women and the eighth leading cause of cancer death. Endometrioid tumors are usually less aggressive, while uterine serous tumors are more aggressive.

There has been little agreement among doctors over the best treatment approach following surgery for patients with a high risk of recurrence, with decisions relying largely on a tumor’s pathology. However, it is difficult for pathologists to reliably differentiate high-grade endometrioid tumors from uterine serous tumors.

According to Dr. Levine, incorporating new genomic information into treatment planning could be a great leap forward, helping to make certain that additional therapies are used effectively and only when necessary.

This year, an estimated 49,560 women in the United States will be diagnosed with uterine endometrial cancer. It is estimated that 8,190 deaths from this disease will occur this year. Uterine cancer is the fourth most common cancer and the eighth most common cause of cancer death for women in the United States. Although uterine cancer rates are higher among white women than black women, black women are more likely to die from uterine cancer than white women.

The one-year relative survival rate (percentage of people who survive at least one year after the cancer is detected, excluding those who die from other diseases) for uterine cancer is 92%. The five-year survival rate for a woman with a local (without spread) uterine cancer at diagnosis is about 95%. If the cancer is diagnosed with regional spread, the five-year survival rate is about 67%, and if diagnosed after the cancer has spread more distantly, it is 16%.

Cancer survival statistics should be interpreted with caution. These estimates are based on data from thousands of people with this type of cancer in the United States each year, but the actual risk for a particular individual may differ. It is not possible to tell a woman how long she will live with uterine cancer. Because the survival statistics are measured in multi-year intervals, they may not represent advances made in the treatment or diagnosis of this cancer. Learn more about understanding statistics.

Statistics adapted from the American Cancer Society’s publication, Cancer Facts & Figures 2013.

The analysis of 373 endometrial tumors showed that approximately a quarter of high-grade endometrioid tumors have certain types of genomic alterations also found in uterine serous tumors. This suggests that a significant portion of endometrioid tumors should be treated more aggressively after surgery.

Many of the tumors analyzed had mutations in important cancer-related genes and pathways for which targeted therapies are already being tested in clinical trials for other cancers. For example, 84 percent of the tumors have some alteration in the PI3 kinase pathway, which is implicated in many cancers. Additionally, genomic alterations in uterine serous tumors share many features with ovarian serous and triple-negative breast cancers, suggesting opportunity for shared treatments.

Endometrial cancer: Incidence

Endometrial cancer is the fourth most common cancer in women in the UK. In 2009, 7,837 women were diagnosed with cancer of the endometrium, or womb lining.

This type of cancer does not affect men, as they do not have an endometrium.

Endometrial cancer: Mortality

Endometrial cancer is the ninth most common cause of cancer death in women in the UK. In 2010, 1,920 women died of endometrial cancer.

Investigators at Memorial Sloan-Kettering are now translating these findings into clinically useful tests that may be applied to ongoing and planned clinical trials.

A project jointly funded by the National Cancer Institute and the National Human Genome Research Institute, TCGA is one of the most comprehensive national efforts to collect and analyze the largest set of tumor samples to date using state-of-the-art genomic and molecular techniques. Memorial Sloan-Kettering currently houses one of TCGA’s Genome Data Analysis Centers, led by computational biologist Chris Sander, PhD, biocomputing manager Nikolaus Schultz, PhD, and molecular pathologist Marc Ladanyi, MD. For the endometrial cancer study, Memorial Sloan-Kettering contributed more than 10 percent of all tissue samples analyzed.

This research was supported by the National Cancer Institute of the National Institutes of Health (NIH) under awards 5U24CA143840-04.

Uterine Cancer Statistics
Uterine cancer is a disease effecting the female reproductive system. Like many other diseases, cancer statistics shows that the best chance of survival comes with early detection. Uterine cancer cases dealing with advanced stages have a dramatically decreased survival rate. In 2009, cancer statistics reveal that 41,200 women will be diagnosed with uterine cancer. About 7,350 women die in an average year from uterine cancer in the United States. The average age of women diagnosed with uterine cancer is 63 years old. Patients who are diagnosed while the cancer is still localized in the uterus have a 96.1% five year survival rate. Patients diagnosed after the cancer has reached the lymph nodes have a 66.3% chance of surviving five years beyond diagnosis. Patients suffering from stage 4 cancer (meaning the uterine cancer has reached distant sites in the body) have about a 25% chance of living past the five year survival rate. These cancer statistics are based on nationwide averages, however, circumstances will be different for all cancer patients. Cancer statistics are meant to aid in peoples’ understanding about the disease and its survival rate. 


Memorial Sloan-Kettering Cancer Center

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