Understanding dMMR Endometrial Cancer

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

What is dMMR endometrial cancer?

Endometrial cancer, sometimes called uterine cancer, starts in the lining of the uterus, called the endometrium. Some of these uterine 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 doesn't work properly, it's called deficient mismatch repair, or dMMR. dMMR cancers tend to have many DNA errors, which can make tumors grow and spread more quickly.^1,3

What increases your risk of developing 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. People with Lynch syndrome have up to a 70 percent chance of developing endometrial cancer in their lifetime.^1,4

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

Treatment options for dMMR endometrial cancer

For decades, surgery, hormone therapy, chemotherapy, and radiation have been the standard treatments for endometrial cancer. Today, that landscape is changing. 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

How immunotherapy works

Immunotherapy drugs help the immune system recognize and attack cancer cells. Recent studies show that dMMR tumors produce abnormal proteins that attract immune cells. Because of this, immunotherapy is a promising treatment option for dMMR endometrial cancer.^1,3

What's new in dMMR endometrial cancer treatment

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

Treatment combinations for dMMR endometrial cancer

For those with dMMR endometrial cancer, one potential option is combining chemotherapy with an immunotherapy drug. Some people may also be treated with immunotherapy alone. More research is needed to understand:^1,2

• How long a person should stay on certain treatments
• What maintenance therapy may be required in specific situations

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 your tumor. Talk to your doctor about the right treatment for you.