From the Guidelines
Li-Fraumeni syndrome is a rare hereditary cancer predisposition disorder characterized by an increased risk of developing multiple types of cancer at an early age, and management involves intensive cancer surveillance protocols starting in childhood, including regular physical examinations, blood tests, imaging studies (MRI, ultrasound), and prompt evaluation of any concerning symptoms, as recommended by the most recent guidelines 1.
Key Characteristics of Li-Fraumeni Syndrome
- Caused by germline mutations in the TP53 tumor suppressor gene
- Increased risk of developing multiple types of cancer, including breast cancer, soft tissue sarcomas, osteosarcomas, brain tumors, adrenocortical carcinomas, and leukemias
- Autosomal dominant inheritance pattern, meaning a person needs only one copy of the mutated gene to be affected
- Each child of an affected parent has a 50% chance of inheriting the mutation
Cancer Surveillance Protocols
- Regular physical examinations
- Blood tests
- Imaging studies (MRI, ultrasound)
- Prompt evaluation of any concerning symptoms
- Annual whole-body MRI and 6-monthly complete blood count may be considered, as recommended by recent guidelines 1
Importance of Genetic Counseling
- Essential for affected families to understand inheritance risks
- Helps with family planning decisions
- Recent studies have emphasized the importance of genetic counseling in Li-Fraumeni syndrome, highlighting the need for personalized risk assessment and management plans 1
Recent Recommendations
- The American Association for Cancer Research recommends that all patients with Li-Fraumeni syndrome be offered cancer surveillance as soon as the clinical or molecular diagnosis is established 1
- The Oncologically Relevant Findings Reporting and Data System (ONCO-RADS) recommendations promote standardization and diminish variations in the acquisition, interpretation, and reporting of whole-body MRI scans obtained for cancer screening in individuals with cancer predisposition syndromes, including Li-Fraumeni syndrome 1
From the Research
Definition and Overview of Li-Fraumeni Syndrome
- Li-Fraumeni Syndrome (LFS) is a rare autosomal dominant familial cancer syndrome caused by germline mutations of the tumor protein p53 gene (TP53) 2.
- It is characterized by a high risk of developing multiple types of cancer, including sarcomas, leukemia, breast malignancies, brain tumors, and adrenocortical cancers 2, 3.
- The lifetime risk of cancer in individuals with LFS is greater than 70% in males and greater than 90% in females 2.
Cancer Risks and Types Associated with Li-Fraumeni Syndrome
- Patients with LFS are at increased risk of developing early-onset gastric and colon cancers, as well as cancers involving the thyroid, lungs, ovaries, and skin 2.
- Osteosarcoma and rhabdomyosarcoma are the most common sarcomas associated with LFS 2.
- LFS is also associated with an increased risk of lymphoid and myeloid leukemias, myelodysplastic syndrome, and lymphoma 3.
Screening and Surveillance for Li-Fraumeni Syndrome
- Whole-body MRI is the preferred modality for annual screening of patients with LFS 4, 2, 5.
- Surveillance with whole-body MRI has been shown to be effective in detecting cancers in asymptomatic patients with LFS, with an estimated detection rate of 6% 5.
- The use of whole-body MRI for screening has been recommended due to its ability to detect cancers at an early stage, improving diagnosis and treatment outcomes 5.
Management and Treatment of Li-Fraumeni Syndrome
- Management guidelines for patients with LFS vary, and these individuals are more susceptible to developing radiation-induced cancers 2.
- Radiation therapy should be avoided in patients with LFS if possible, due to the inability to repair DNA damage 6.
- A surveillance system using whole-body MRI is recommended for patients with LFS, and genetic counseling is also important for families with a history of LFS 6.