Genomics to reshape endometrial cancer treatment

The most in-depth look yet at endometrial cancer shows that adding genomics-based testing to the standard diagnostic workup could change the recommended course of treatment for some women.

The new research, involving nearly 400 women with endometrial cancer, is published May 2 in the journal Nature. The endeavor is part of The Cancer Genome Atlas project, funded by the National Institutes of Health (NIH).

The study also indicates that some endometrial tumors are genetically similar to subtypes of ovarian cancer and deadly basal-like breast cancer. Future clinical trials should evaluate whether some endometrial cancers could be treated with drugs typically used for the other cancers, says project co-leader Elaine Mardis, PhD, co-director of The Genome Institute at Washington University School of Medicine in St. Louis. The other co-leader is Douglas A. Levine, MD, of the Memorial Sloan-Kettering Cancer Center.

A second Cancer Genome Atlas paper will be published May 1 in the New England Journal of Medicine. That research, also led by Washington University, describes finding virtually all the major mutations involved in acute myeloid leukemia.

While gynecologic oncologists have long recognized two subtypes of endometrial cancer, one more aggressive than the other, the new data reveal four novel subtypes and also suggest that the frequency of mutations in a tumor could be used to help guide treatment decisions.

"We are entering an era when tumors can be evaluated from a genomics standpoint, not just by looking at cancer cells under a microscope," Mardis says. "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."

As part of the new research, a consortium of researchers analyzed tumors from 373 women with endometrial cancer using different technologies to look for defects in DNA, RNA (a close chemical cousin of DNA) and proteins.

Their analysis indicates that about 25 percent of women with endometrial cancer who are thought to have a favorable prognosis based on pathology reports instead have a more formidable form of the disease, based on underlying genetic changes, and should be treated aggressively.

Clinically, endometrial cancers fall into two categories: endometrioid and serous. Endometrioid cancers generally are associated with excess estrogen, obesity and a favorable prognosis. In contrast, serous endometrial cancers are more common in older women and generally have poorer outcomes.

After surgery to remove endometrial cancer, women with the endometrioid subtype typically are treated with radiation therapy to kill remaining cancer cells, while those with serous tumors receive a more aggressive treatment – chemotherapy.

Doctors distinguish between the two tumor subtypes by evaluating cancer cells under a microscope. But categorizing some tumors is difficult, and pathologists don't always agree.