What Is dMMR Endometrial Cancer and Who Is at Risk?

Endometrial cancer is the most common type of gynecological cancer in the United States, accounting for about 66,000 new cases each year. And it is the sixth most common cancer worldwide. About 20 to 30 percent of endometrial cancer is caused by a deficiency in the MMR pathway (dMMR).¹

What is dMMR endometrial cancer?

Endometrial cancer starts in the lining of the uterus, called the endometrium. Some of these cancers have a feature known as deficient mismatch repair (dMMR).^1,2

Mismatch repair is a system within our cells that fixes DNA damage. When this system does not work properly, it is called deficient mismatch repair, or dMMR. Cancers with dMMR tend to have many DNA errors, which can make tumors grow and spread more quickly.^1,3

Who is at risk of endometrial cancer?

Several factors can increase the risk of developing endometrial cancer, including:^1,4

• Genetic conditions – Lynch syndrome and Cowden’s syndrome are 2 hereditary disorders that raise the risk of endometrial cancer.
• Family history – A family history of endometrial or colorectal cancer can potentially suggest a higher risk, possibly due to inherited genetic mutations.
• Previous cancers – Having had breast or ovarian cancers in the past can increase the risk for endometrial cancer.
• Other risk factors – Obesity, type 2 diabetes, things that affect hormone levels, and never having been pregnant are also linked to a higher risk of endometrial cancer.

Can the dMMR mutation be passed down to family members?

Yes, mutations in mismatch repair genes can be inherited. Lynch syndrome, for example, is passed down in families through mutations in genes like MLH1, MSH2, MSH6, and PMS2. For those with Lynch syndrome, there is up to a 70 percent chance of developing endometrial cancer during their lifetime.^1,4

If a parent carries a mutation in one of these genes, there is a chance it will be passed to their children. Genetic counseling and testing can help determine if someone has inherited these mutations.

Treatment options for dMMR endometrial cancer

For decades, surgery, hormone therapy, chemotherapy, and radiation have been the standard treatment for endometrial cancer. Today, precision-based therapies like immunotherapy can target the specific molecular subtypes of a person’s tumor. This has resulted in improved outcomes and survival rates.^1,3

Immunotherapy drugs help the immune system recognize and attack cancer cells. According to recent studies, because dMMR tumors produce abnormal proteins that attract immune cells, immunotherapy is a promising treatment option.^1,3

There is a lot of hope in the treatment space for endometrial cancer. Emerging therapies and new drugs have been approved by the US Food and Drug Administration (FDA) for use in people with advanced or recurrent endometrial cancer.^1,2

For those with dMMR endometrial cancer, one potential treatment option is a combination of chemotherapy with an immunotherapy drug. Some people may also be treated with immunotherapy alone. More research is needed to understand how long a person should stay on certain treatments and what maintenance therapy may be required in specific situations.^1,2

Questions to ask your doctor about dMMR endometrial cancer

If you are diagnosed with dMMR endometrial cancer, consider asking your doctor:

• What does my dMMR status mean for my treatment options?
• Should I undergo genetic testing for Lynch syndrome?
• What are the potential side effects of the recommended treatments?
• How will treatment affect my daily life and fertility?
• How long will I have to stay on the recommended treatment?
• Are there any clinical trials available that I should consider?
• What is my prognosis, and how does dMMR status influence it?

Understanding dMMR endometrial cancer can help you make informed decisions about your health. The choice of treatment depends on factors like the cancer's stage, overall health, and specific characteristics of the tumor. Talk to your doctor about the right treatment for you.