Li-Fraumeni Syndrome

Li-Fraumeni syndrome (LFS) is a rare hereditary condition that increases your risk of developing multiple cancers, often at an early age. It is caused by a change or mutation in a gene that can be passed down in families.

People with LFS have a 50% chance of passing the syndrome to their children. Cancers most often associated with LFS include adrenal gland, brain, breast, gastrointestinal, leukemia, melanoma, osteosarcoma and soft tissue sarcomas.

The University of Kansas Cancer Center and Children’s Mercy Kansas City have established the Heartland's Li-Fraumeni Syndrome program to provide seamless leading-edge care and surveillance across the age continuum from children to adults. Heartland's LFS care team includes certified genetic counselors, pediatric and adult medical oncologists, geneticists and coordinated nurse navigation.

As the region’s only National Cancer Institute-designated comprehensive cancer center, we offer a multidisciplinary team approach to identify individuals who have LFS. Taking this step helps ensure that you receive appropriate cancer screening, which can improve the chances of preventing or diagnosing cancers early, when they are most treatable.

LFS is a hereditary cancer syndrome that puts children and adults at high risk for developing multiple cancers, including adrenal cortical carcinoma, brain tumors, early-onset breast cancer and sarcomas. The condition is rare, affecting 1 in 5,000 to 1 in 20,000 people worldwide.

About one-third of LFS-related cancers occur before age 18, half before age 30 and most by age 50. In the general population, cancer typically occurs in people over age 60.

The syndrome is most often caused by an inherited mutation in the TP53 gene, which is a tumor suppressor gene. A normal TP53 gene makes a protein that helps stop abnormal cells from growing. When a mutation occurs in the TP53 gene, the damaged gene is no longer able to prevent abnormal cells from dividing uncontrollably and becoming cancer.

If you are diagnosed with LFS, you have a 90% chance of developing 1 or more types of cancer in your lifetime and a 50% chance of developing cancer before age 30. Having LFS means cancers often occur at a young age, even in childhood.

People with LFS are also up to 50% more likely to develop 2 or more separate cancers. These distinct cancers may occur at the same time or years apart. Studies show people who have had radiation treatment are at higher risk of developing a second cancer.

People with LFS have an increased risk of the following types of cancer:

• Adrenal gland
• Breast
• Brain and Central Nervous System
• Gastrointestinal
• Leukemia
• Melanoma
• Osteosarcoma
• Soft tissue sarcomas

LFS is usually suspected if you are diagnosed with a sarcoma before age 45, or if you have family members diagnosed with any cancer who are under age 45. In such situations, we would likely advise genetic counseling and genetic testing.

LFS may also be considered if you have a personal or family history of cancers common among LFS carriers (see above list). In addition, certain rare cancers are characteristic of the syndrome and should alert physicians to a possible LFS diagnosis. These include adrenocortical carcinoma, choroid plexus carcinoma, anaplastic rhabdomyosarcoma, sonic hedgehog medulloblastoma, hypodiploid acute lymphoblastic leukemia, osteosarcoma or breast cancer in young women.

If you or your family has experienced multiple childhood cancers, or particularly rare cancers including early-onset cancers, you should have genetic testing to determine if you have LFS. An early diagnosis is critical and enables affected families to seek genetic counseling as well as surveillance for early detection. An early diagnosis of LFS can be lifesaving.

LFS diagnosis and screening

Talk to your doctor about your family health history and individual concerns to create a personalized cancer screening plan. At The University of Kansas Cancer Center, our cancer genetics experts can identify individuals who have LFS and ensure they receive appropriate cancer screening. This can improve the chances of preventing or diagnosing cancers early when they are most treatable.

If you have a TP53 mutation, your family members might have it, too. Talk to your parents, siblings and children about getting tested for LFS. Even if they choose not to have genetic testing, they may want to start screening for certain cancers early or take other precautions to lower their risk of cancer.

To learn if you might benefit from genetic testing, connect with one of our nurse navigators at 913-588-3671 who can assist you with scheduling an appointment with a cancer provider.

Reducing your cancer risk

• Talk to your doctor about cancer screenings you should receive, including what age to begin, types and frequency.
• There are different screening schedules for children and adults diagnosed with LFS.
• Screenings for children focus on adrenocortical carcinomas, brain, soft tissue and bone cancers.
• Screenings for adults focus on breast, brain, soft tissue, bone, skin and gastrointestinal cancers.
• People with LFS have a higher risk of developing cancer from radiation exposure, so doctors advise them not to have any imaging or treatments that include radiation.
• Talk to your doctor about steps you can take to lower your cancer risk, such as maintaining a healthy weight, being physically active and limiting alcohol.

Since people diagnosed with LFS are prone to developing multiple cancers, you should ensure you maintain a healthy lifestyle, including sun protection and avoiding tobacco products.

Early cancer detection can greatly increase overall survival. If you’ve received a diagnosis of LFS, talk to your doctor about preventive screenings you should receive, including whole-body MRI, as soon as your LFS diagnosis is established.

The University of Kansas Cancer Center and Children’s Mercy have established the Heartland's Li-Fraumeni Syndrome program to provide seamless leading-edge care and surveillance across the age continuum from children to adults. The Heartland’s LFS care team includes pediatric and adult medical oncologists, gastroenterologists, geneticists, genetic counselors and coordinated nurse navigation.

As an NCI-designated comprehensive cancer center, we are committed to making a difference for patients using the latest, most advanced cancer treatments, innovative therapeutics and chemoprevention. In addition to standard care and treatments, we perform clinical research studies to help find better ways of preventing, diagnosing and treating various types of cancer.