Harvard Model Identifies Women at High-Risk For Endometrial Cancer

Endometrial cancer is the most common form of uterine cancer and the fourth most frequent cancer diagnosis in women throughout the United States. A new study shines a light on recognizing high-risk individuals.

Key takeaways:

A team of Harvard researchers identified those at increased risk of endometrial cancer through their new prediction model.

Screening guidelines do not recommend evaluating those with Lynch syndrome for endometrial cancer, according to the CDC. Lynch syndrome is responsible for 4,200 colorectal and 1,800 uterine (endometrial) cancers per year.

What is endometrial cancer?

The specific cause of endometrial cancer is unknown, but it occurs after mutations to DNA cells in the uterus lining. The mutations make healthy cells abnormal cells that grow and multiply uncontrolled and die simultaneously, which is the opposite of normal cells. A growing number of abnormal cells creates a tumor.

The American Cancer Society says the average age of patients with endometrial cancer is 60 years old, with cases under 45 to be rare.

To reduce the chances of endometrial cancer, the CDC highlights birth control pills, maintaining a healthy lifestyle, and progesterone to those consuming estrogen as possible prevention steps. However, there is no definitive measure to prevent the onset of the disease.

Risks factors for endometrial cancer:

  • Never becoming pregnant
  • Starting menstruation at a younger age
  • Older age
  • Unhealthy weight or obese
  • Hormone therapy during breast cancer
  • Inherited colon cancer syndrome such as Lynch syndrome

Harvard findings

The Harvard model is the most extensive, heterogeneous international study that has been completed. Two past risk-model probes were conducted on selective study populations and failed to produce a history of diabetes, education, hypertension, or use of hormonal therapy.

Harvard researchers believe their model will serve as the framework for the development of a risk prediction tool for clinical public health practice, and assess genetic factors for higher risk of endometrial cancer.

The investigation featured 19 case-control studies in the Epidemiology of Endometrial Cancer Consortium. Participants varied worldwide, including the United States, Canada, Europe, China, and Australia. The research was limited to postmenopausal white women aged 45 to 85 years.

Researchers successfully predicted the individuals at higher risk for endometrial cancer using a statistical tool called LASSO. Following this step, the Harvard team translated those risks into an absolute risk prediction to discover the likelihood of an individual developing the disease in the next decade.

Their findings were confirmed by data from 121,700 female registered nurses aged 30 to 55 years in the Nurses’ Health Study, 116,430 female registered nurses aged 25 to 42 years from the Nurses’ Health Study II, and 78,232 women aged 55 to 74 years from the Prostate, Lung, Colorectal and Ovarian Screening Trial.

Individuals involved in those three cohorts were followed for 10 years, with questionnaires, death records, and medical records used to confirm a diagnosis of endometrial cancer by pathologists and physicians.

Senior author and professor of Medicine at Harvard Medical School, Immaculata De Vivo, M.P.H., Ph.D., highlights the importance of the three data sets on their findings in a university news release.

"NHS, NHSII, and PLCO are cohorts with uniquely rich datasets, with data on tens of thousands of participants over decades of follow-up," De Vivo said. "There is also genetic data available for many of these study participants, which allowed us to investigate the potential contributions of genetic factors in predicting endometrial cancer risk."

Their results found the average cumulative risk of endometrial cancer for women between 45 and 85 to be 5.4%. Women with few genetic factors leading to endometrial cancer had a risk of less than 2% of developing the disease. Meanwhile, women with more epidemiologic risk factors had the highest chance of developing endometrial cancer at 13.7% to 15.01%.

When their risk model was used on a more relative sample of U.S., white women, those in the 97th percentile of risk had a greater than 20% chance of developing endometrial cancer. That is similar to the percentage of risk for individuals with Lynch syndrome.

Although the study is a massive step forward, more research is needed to see how successful the model is with different races. While white women make up 72% of endometrial cancer cases in the U.S., the American Cancer Society says Black women are more likely to attain and die from the disease.


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