From the Guidelines
Li-Fraumeni syndrome is a rare hereditary disorder that requires comprehensive cancer surveillance starting in childhood, including regular physical examinations, blood tests, imaging studies (MRI, ultrasound), and colonoscopies, as recommended by the NCCN guidelines 1.
Key Points
- Individuals with Li-Fraumeni syndrome have a significantly higher lifetime risk of developing cancers including breast cancer, sarcomas, brain tumors, adrenocortical carcinomas, and leukemias.
- The syndrome is caused by mutations in the TP53 gene, which normally functions as a tumor suppressor by regulating cell growth and division.
- Management involves early detection through surveillance, which is crucial for improved outcomes.
- Genetic counseling is essential for affected individuals and their families to understand inheritance patterns (autosomal dominant) and testing options.
- Family members should be offered genetic testing since each child of an affected parent has a 50% chance of inheriting the mutation.
- Lifestyle modifications such as avoiding radiation exposure when possible, maintaining a healthy weight, limiting alcohol consumption, and avoiding tobacco can potentially reduce cancer risks in these individuals.
Surveillance Recommendations
- The NCCN guidelines recommend annual whole-body MRI for cancer screening in pediatric subjects with TP53 germline mutation 1.
- The American Association for Cancer Research recommends adoption of a modified version of the "Toronto protocol" that includes a combination of physical exams, blood tests, and imaging 1.
- The expert panel concludes that there are sufficient existing data to recommend that all patients with LFS be offered cancer surveillance as soon as the clinical or molecular LFS diagnosis is established 1.
From the Research
Definition and Causes 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, 3, 4, 5, 6.
- The TP53 gene encodes the p53 transcription factor, also known as the "guardian of the genome" 2.
- Mutations in the TP53 gene prevent it from functioning properly, leading to the development of various malignancies throughout life 5, 6.
Types of Cancer Associated with Li-Fraumeni Syndrome
- The most common types of cancer found in families with LFS include sarcomas, leukemia, breast malignancies, brain tumors, and adrenocortical cancers 2, 3, 4.
- Osteosarcoma and rhabdomyosarcoma are the most common sarcomas associated with LFS 2, 6.
- Patients with LFS are also at increased risk of developing early-onset gastric and colon cancers, as well as cancers involving the thyroid, lungs, ovaries, and skin 2.
Screening and Management Guidelines
- Whole-body MRI is the preferred modality for annual screening of patients with LFS 2, 4.
- Guidelines have been established for screening patients with LFS, and management guidelines vary depending on the individual's susceptibility to radiation-induced cancers 2, 4.
- Women with LFS and breast cancer are treated with total mastectomy instead of lumpectomy with radiation to the breast to minimize the risk of radiation-induced cancers 2.