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%.