ID-ing Lynch Syndrome in Women with Endometrial Cancer Saves Lives and is Cost-Effective

45,000 women were diagnosed with endometrial cancer in the United States in 2010 — and for nearly 900, cancer was due to Lynch syndrome.

Women who have Lynch syndrome have an increased risk of getting endometrial cancer during their lifetime that is as high as 60 percent. Often endometrial cancer (cancer of the lining of the uterus) is the first Lynch-related cancer diagnosed, earlier than colon or rectal cancer.

Identifying a mutation in these women can prevent future colorectal cancers and discover ovarian, gastric, and other Lynch cancers early when they can be treated successfully.

And not only does this help the woman with endometrial cancer, it helps her family as well if they are tested for the inherited mutation and take steps to reduce their risk of future cancers.

Now, a research team has found the most cost-effective way to identify those women with endometrial cancer with Lynch syndrome is to screen their tumors for missing Lynch proteins only if they also have a first-degree relative with a Lynch-related cancer.

Researchers from the University of British Columbia and MD Anderson Cancer Center in Texas built a computer model to study ways to find women with Lynch syndrome among all women diagnosed with endometrial cancer.  Their goal was to decide on the best strategy to identify both:

  • The most women with Lynch syndrome at risk for future colorectal cancer.
  • The most cost-effective way of finding those women.

The six strategies they considered were:

  • Direct referral for genetic testing for women with Amsterdam II family histories.
  • Direct referral to genetic testing for women diagnosed under age 50 with at least one first-degree relative with a Lynch-related cancer.
  • Immunohistochemical triage (IHC) of tumors in women under age 50 with genetic testing for those positive.
  • IHC triage for women under age 60, followed by genetic testing for positive results.
  • IHC triage for women diagnosed at any age with one first-degree relative with a Lynch cancer, followed by genetic testing.
  • IHC triage for all women with endometrial cancer, with follow-up of positive results with genetic testing.

While using immunohistochemical testing for all women with diagnosed at any age with endometrial cancer would find 100 percent of Lynch syndrome, it is extremely expensive with an incremental cost-effectiveness ratio (ICER) of $648,494 for each life-year gained.

A better strategy was to use IHC triage for all women diagnosed at any age, but limit the tests to those who had a first-degree relative (parent, child, sibling) with a Lynch-related cancer.  The ICER for this plan was $9,126 — well within the range of cost-effective public health benefits.  It would also find more than 91 percent of women with Lynch syndrome

  • Using the Amsterdam family history criteria would miss about a third of women (35%) who have Lynch syndrome.
  • Direct genetic testing without IHC triage for women under 50 with a first-degree relative with a Lynch cancer would also miss 36% of potential Lynch mutations.
  • IHC triage of women under 50 and under 60 would miss 38% and 34% of women with Lynch syndrome respectively.

Colonoscopy screening saves lives

Both women with Lynch syndrome and women with sporadic endometrial cancer benefit from colonoscopy screeningto reduce their subsequent risk for colorectal cancer and death from colorectal cancer:

  • Lynch syndrome women who have annual colonoscopies have a 15% risk of getting colorectal cancer and a 6% risk of dying from it.
  • LS women who don’t get the critical annual colonoscopy surveillance have a 40% risk of getting colorectal cancer and a 47% chance of dying.
  • Women with sporadic endometrial cancer who have at least one colonoscopy every 10 years cut their risk of colorectal cancer from 5% to 3% compared to women who don’t get a colonoscopy.  Their chances of dying of colorectal cancer are cut down from 37% to 15%.

Janice S. Kwon, MD, MPH, FRCSC and her colleagues concluded,

Immunohistochemical (IHC) triage of women with endometrial cancer at any age having at least 1 first-degree relative (FDR) with a Lynch-associated cancer is a cost-effective strategy for detecting Lynch syndrome. IHC triage of women with endometrial cancer at any age having at least 1 FDR with a Lynch-associated cancer is a cost-effective strategy for detecting Lynch syndrome.


Kwon et al., Journal of Clinical Oncology, Volume 29, Number 16, June 1, 2011.

What This Means for Patients

If you have been diagnosed with endometrial cancer — cancer of the uterine lining — at any age and also have a parent, sister or brother, or child who has been diagnosed with a Lynch-syndrome related cancer, you should ask to have your tumor tested first by immunohistochemistry to see if you might have Lynch syndrome.

If that initial test is positive, you should follow-through with genetic testing to see if you have an inherited mutation for Lynch syndrome.

This is a better strategy than depending on family history alone or being diagnosed under age 50.

Lynch syndrome related cancers include colon, rectal, ovarian, endometrial, gastric, small bowel, and brain cancer as well as some kidney and skin cancers.  Newer evidence points to breast cancer as also related to Lynch syndrome.

Everyone needs to be aware of of how important including anyone with endometrial cancer when family histories are taken





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