Li-Fraumeni Syndrome

February 12, 2026

This page was reviewed under our medical and editorial policy by Heather Hampel, M.S., C.G.C., professor; and Bita Nehoray, M.S., C.G.C., manager, genetic counseling, Department of Medical Oncology & Therapeutics Research, City of Hope^® Cancer Center Duarte.

Li-Fraumeni syndrome (LFS) is a rare cancer susceptibility condition that runs in families. It is caused by a harmful gene change (mutation) that is passed down from one family member to another. LFS increases the risk for several cancer types.

Li-Fraumeni syndrome is generally considered to affect 1 in 3,000 to 1 in 10,000 individuals. A high prevalence of a specific tumor protein 53 (TP53) gene variant exists in Southern and Southeastern Brazil, increasing the local frequency.

What Is Li-Fraumeni Syndrome?

Li-Fraumeni syndrome is a genetic disorder that increases the risk for a broad spectrum of cancer types throughout an individual's lifetime, with the most common (core cancers) being sarcoma, breast cancer, brain cancer, leukemia and adrenocortical gland cancers. It is most often caused by an inherited mutation in the TP53 gene, a gene responsible for suppressing tumors. Normally, the TP53 gene produces a protein that helps stop abnormal cells from growing, but when a change occurs in the TP53 gene, abnormal cells may divide uncontrollably and become tumors.

Because LFS is an inherited syndrome, it may be passed down in families. LFS is typically diagnosed when a person suspected of having it undergoes genetic testing to determine whether he or she has an inherited TP53 gene mutation.

Developing certain cancers at an early age is the most common sign of Li-Fraumeni syndrome. LFS is more likely in people who develop the core cancers under the age of 50, particularly for those individuals who also have a close family member diagnosed with cancer at an early age. Given the higher likelihood, health care providers often recommend genetic counseling and genetic testing for this population.

Li-Fraumeni Syndrome Cancers

Li-Fraumeni syndrome significantly increases the risk that a patient and his or her family members will develop cancer. LFS patients have about a 50% chance of developing cancer by the time they turn 40, and that risk rises to 90% by the time they turn 60. Females with LFS have a very high risk for developing breast cancer.

Some people with LFS develop two or more cancers through the course of their lifetime. Cancers most closely associated with LFS, known as core cancers, include:

• Soft tissue sarcoma
• Osteosarcoma
• Breast cancer
• Brain and central nervous system tumors
• Adrenocortical carcinoma
• Acute leukemia

Other cancers associated with LFS, but which occur less often than the core cancers, include:

• Lung adenocarcinoma
• Melanoma
• Gastrointestinal cancers (such as colon, stomach and pancreatic cancer)
• Prostate cancer
• Thyroid cancer
• Kidney cancer
• Gonadal germ cells (such as ovarian and testicular cancer)

Genetic Testing

Early detection of Li-Fraumeni syndrome may be life-saving, allowing affected families to take appropriate next steps, including genetic counseling, genetic testing, cancer screening and/or opportunities for cancer prevention.

While not everyone with a TP53 gene mutation will develop cancer, the risk is significantly higher compared to the general population. If someone has a TP53 mutation, there’s a chance some of his or her blood-related family members have it too. That’s why talking to these relatives (parents, siblings and children) about getting tested for LFS is critical.

When it comes to genetic testing, it’s important to have conversations with the health care team, a genetic counselor and family. Together, the decision will be made about whether a person should be tested for a TP53 gene mutation.

Cancer Screening

Consistent cancer screenings play a key role in managing LFS’s impact on a person’s life and his or her family’s lives.

There are different cancer screening recommendations for children and adults with LFS. For children, screenings focus more on surveillance for adrenocortical carcinomas, brain tumors, leukemias, soft tissue cancers and bone cancers. For adults, they focus more on looking for brain, breast, soft tissue, bone, skin and gastrointestinal cancers.

Some experts recommend that people with LFS get screened according to the following guidelines:

• A comprehensive physical examination, including a neurologic examination, every six to 12 months
• Whole body monitoring, including a magnetic resonance imaging (MRI) scan of the whole body, once a year
  • An annual brain MRI may be performed as part of the whole body MRI or as a separate exam
  • An annual skin examination by dermatology is recommended
• Complete blood count with differential every three to six months
• Breast cancer monitoring, including monthly self-exams, clinical breast exams twice a year and annual breast MRI with and without contrast starting at age 20 and annual mammography starting at age 30. In addition, some women choose to undergo a risk-reducing bilateral mastectomy
• Colonoscopy or upper endoscopy every two to five years, starting at age 25, or five years prior to the earliest known colorectal or gastric cancer occurring in the patient’s family
• Annual prostate-specific antigen (PSA) starting at age 40 for prostate cancer early detection
• Pancreatic cancer surveillance with annual endoscopic ultrasound and MRCP starting at age 50 if the patient has a close family history of pancreatic cancer

It’s important to know that LFS patients have a higher risk of getting cancer from radiation exposure, and doctors often advise them to avoid radiation-related treatments if possible. Speak with the care team to evaluate whether any particular cancer screenings are recommended, as well as the suggested frequency of those tests.