Cowden Syndrome

The risk for breast cancer is increased with Cowden syndrome. This is a rare inherited disorder that is also associated with certain noncancerous features. Cowden syndrome is associated with the following characteristics:

• Multiple hamartomatous growths (benign [noncancerous] tumors of normal tissue) of the skin and other organs, usually present in women by their late 20s
• Macrocephaly (increased head size)
• Increased risk of breast cancer, with an average age of onset ranging from 38 to 46 years old
• Increased risk of thyroid cancer
• Increased risk of endometrial cancer
  
  

Other features can include noncancerous thyroid growths, intestinal polyps, lipomas (benign fatty tumors), fibromas, uterine fibroids, and fibrocystic disease of the breast.

What causes Cowden syndrome?

Cowden syndrome is caused by mutations in a gene on chromosome 10 known as PTEN. About 80 percent of people whose symptoms meet the criteria for a diagnosis of Cowden syndrome have a PTEN mutation. People with a PTEN mutation have a 25 percent to 50 percent lifetime risk of breast cancer. They also have about a 10 percent risk of thyroid cancer and perhaps up to a 10 percent risk of uterine cancer, although this risk is still being studied.

The PTEN gene is a type of tumor suppressor gene. It usually controls cell growth and cell death. Both copies of a tumor suppressor gene must be altered (mutated) before a person will develop cancer. With Cowden syndrome, the first mutation is inherited from either the mother or the father. It is therefore present in all cells of the body. This is called a germline mutation.

Whether a person who has a germline mutation gets cancer and where the cancer develops depends on where (which cell type) the second mutation occurs. For example, if the second mutation is in the thyroid, then thyroid cancer may develop. If it is in the breast, breast cancer may develop. But other mutations are needed too to lead to cancer. Mutation of both copies of PTEN is just the first step in the process. What causes these additional mutations is unknown. Possible causes include chemical, physical, or biologic agents in the environment or chance errors that happen when cells reproduce.

Some people who have inherited one PTEN mutation never develop cancer because they never get the second mutation. This can make the cancer appear to skip generations in a family, when in reality the mutation is present. People with a mutation, regardless of whether they develop cancer, have a 50-50 chance of passing the mutation on to their children.

The PTEN gene is not located on the sex chromosomes. This means that mutations can be inherited from the mother's or the father's side of the family.

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