Nearly a third of women with certain abnormal uterine lesions later go on to develop endometrial cancer, while most women with other less severe lesions remain cancer free for decades, according to findings from a City of Hope researcher and colleagues nationwide.

James Lacey (Photo by Darrin S. Joy)

Results from the 20-year study, published online Jan. 11 in the Journal of Clinical Oncology, provide much-needed information that may guide important decisions faced by women and their physicians.

“Our data provide the most accurate estimates to date on how likely women with these lesions are to progress to carcinoma during the years after diagnosis,” said James V. Lacey Jr., Ph.D., associate professor in City of Hope’s Division of Cancer Etiology and the study’s lead author. “Knowing those risks can be especially helpful in weighing the pros and cons of various treatments.”

The study followed nearly 8,000 women in the Kaiser Permanente Northwest Health Plan, in Portland, Ore., who were diagnosed with endometrial hyperplasia between 1970 and 2002. Endometrial hyperplasia is an abnormal proliferation of cells in the lining of the uterus. It often is diagnosed after an endometrial biopsy procedure, which uses a thin tube to collect a sample of cells from the endometrial lining.

Pathologists group endometrial hyperplasia into three categories — simple, complex or atypical — based on how the cells appear under a microscope.

They often recommend hysterectomy for women with atypical hyperplasia because as many as half of these women actually have endometrial cancer when atypical hyperplasia is diagnosed. But direction on how to treat women with atypical hyperplasia who do not undergo hysterectomy — or the many more women with simple or complex hyperplasia — is unclear.

In the study, researchers selected 138 women with endometrial hyperplasia who developed cancer at least one year, and on average six years, after their diagnosis of endometrial hyperplasia. They then compared them over time to 241 similar women with hyperplasia who were cancer-free for the same amount of time.

Among their findings:

• About 28 percent of women with atypical hyperplasia untreated through hysterectomy developed endometrial cancer within the next 20 years — even if they were treated through hormone therapy and had follow-up biopsies done.
• Women with either simple or complex hyperplasia had only a 5 percent risk of progressing to endometrial cancer within 20 years.

“For physicians and their patients, knowing absolute risks may help decide whether to pursue definitive treatment — a hysterectomy — or decide on nonsurgical management, including progestin-based therapy and regular observation,” Lacey said.

The findings may help clear uncertainty about how to treat complex hyperplasia in particular, especially among postmenopausal women. The study suggests that hormone therapy and routine follow-up tests were enough for most women with this diagnosis, potentially allowing many women to keep their uteruses.

Lacey noted that scientists now must try to find ways to identify the 5 percent of women with simple or complex hyperplasia who go on to develop cancer. They also hope to better identify early markers of atypical hyperplasia among women with postmenopausal bleeding to catch these cases earlier.

Finally, researchers hope to develop tools or strategies pathologists can use to more quickly and accurately classify abnormal endometrial lesions, which would allow physicians and their patients to make treatment decisions based on more reliable information.

The study was funded by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute (NCI), part of the National Institutes of Health. Collaborators included investigators at the NCI, Johns Hopkins Medical Institutions, University of Maryland Medical Center, Kaiser Permanente Center for Health Research, and Keck School of Medicine of the University of Southern California.