Genomics Help Improve Endometrial Cancer Treatment
May 2, 2013

New Endometrial Cancer Subtypes, Treatment Opportunities Identified

redOrbit Staff & Wire Reports - Your Universe Online

Adding genomics-based testing to standard patient evaluation process could drastically alter the recommended treatment program for women with endometrial cancer, as well as the classification of that form of cancerous tumor, claims research published Thursday in the journal Nature.

As part of the study, investigators from The Cancer Genome Atlas (TCGA) Research Network analyzed endometrial cancer tumor samples from 373 patients using array- and sequencing-based technologies. They discovered that two subtypes of the tumor, uterine serous tumors and high-grade endometrioid tumors, had several genetic mutations in common with each other.

They discovered that approximately one-fourth of tumors that were classified as high-grade endometrioid actually had genetic features similar to uterine serous carcinoma tumors. Among those similarities were extensive copy number alterations and frequent mutations in the TP53 gene, which encodes a tumor-suppressing protein known as p53.

Furthermore, uterine serous carcinomas were found to share genomic features with ovarian serous and basal-like breast carcinomas, the authors said. In the future, they suggest that clinical trials should evaluate whether some endometrial cancers types could be effectively treated using drugs regularly prescribed for the other cancers.

Typically, early stage endometrioid tumors are treated with adjuvant radiotherapy, while chemotherapy is used for similarly staged serious tumors, the researchers said. However, based on the newly discovered genetic similarities, they argue that doctors should consider using chemotherapy rather than adjuvant radiotherapy to treat copy number-altered endometrioid patients — and they suggest clinical trials to formally test their hypotheses.

"Some of the results reported in this paper can change the way endometrial cancers are classified and provide opportunities to test new treatment protocols for patients with this cancer," Raju S. Kucherlapati, a professor of genetics and medicine at Brigham and Women's Hospital and Harvard Medical school, said in a statement.

“We are entering an era when tumors can be evaluated from a genomics standpoint, not just by looking at cancer cells under a microscope,” added project co-leader Elaine Mardis, the co-director of The Genome Institute at Washington University School of Medicine in St. Louis. “This more comprehensive approach provides a clearer picture of the way particular endometrial cancers will behave and will be important to gynecological oncologists who treat this disease.”

According to the TCGA research team, endometrial cancer is the fourth most commonly diagnosed cancer among American women. Roughly 50,000 cases will be diagnosed this year, they said, and an estimated 8,000 women will die as a result of the disease.

Furthermore, for patients who are newly diagnosed with aggressive high-grade tumors which have spread, the five-year survival rate is approximately 16 percent. However, chemotherapy has been linked with improvements in survival, and the medical community is currently testing for new targeted treatment agents, they said.

“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 corresponding author Douglas A. Levine, a gynecologic oncologist at the Memorial Sloan-Kettering Cancer Center and the 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.”

The research was funded by the National Institutes of Health (NIH).