Download Li-Fraumeni Syndrome (LFS)

Li‐Fraumeni Syndrome (LFS) Li‐Fraumeni syndrome (LFS) is a rare genetic condition that can be passed on throughout a family. Individuals with LFS are at higher risk to develop various types of cancer during their lifetime, including in childhood, adolescence, or adulthood. Cancer Risks Individuals with LFS may develop rare tumors or more common tumors at unusually young ages. Cancers associated with LFS include: • Breast cancer • Sarcomas (tumors of muscle, fat, bone) • Brain tumors • Acute leukemia and lymphomas • Adrenal Cortical tumors There also may be an increased risk for melanoma, colon cancer, stomach cancer, esophagus cancer, pancreatic cancer, lung cancer, prostate cancer and germ cell tumors. Other tumors and cancers have been reported. It is not possible to predict the age at which cancer might occur or which type of cancer might develop. Keep in mind that some individuals with LFS never develop cancer. LFS is responsible for less than 1% of all breast cancer cases. However, a woman diagnosed with breast cancer prior to age 30 has a 2‐7% chance of having LFS. This chance may increase if there are other LFS cancers in the patient or in any of her family members. Genetic Basis Mutations (alterations) in the p53 gene cause LFS. Genetic testing is available for the PTEN gene. More than 70% of people who appear to have LFS have a detectable mutation the p53 gene. This means that 30% of the time, the person is believed to have LFS but the genetic testing does not find a mutation. A mutation may, in fact, be there but the current testing technology cannot identify it. Genetic testing requires a blood or saliva sample. Many insurance companies will cover testing when appropriate. Inheritance If someone has LFS, their children, siblings, and parents are each at 50% risk to also have LFS. If genetic testing identifies a mutation in the p53 gene, then relatives can be tested to determine 1
whether they also have the same gene mutation. More distant relatives (aunts/uncles, grandparents, cousins, etc…) are also at‐risk to have LFS. It is important to share genetic test results with family members. If someone does not inherit a p53 gene mutation, then they cannot pass LFS onto their children. Diagnosis There are two ways to diagnose LFS. Patients may fall into one or both categories. 1. Clinical diagnosis ‐ The patient’s signs and symptoms are compared to definite clinical criteria. If a patient meets the clinical criteria, he/she has a diagnosis of LFS. 2. Genetic testing ‐ The patient’s DNA is examined for mutations in the p53 gene. If a mutation in the p53 gene is identified, the patient has a diagnosis of LFS. Cancer Risk Reduction and Prevention Cancer is the primary health risk for patients with LFS. Thus, it is important to screen these individuals carefully for specific cancers. This will help to ensure that cancers are detected at their earliest, most treatable stages. The National Comprehensive Cancer Network (www.nccn.org) recommends the following for individuals with LFS: Type of How often? Age to begin Surveillance Physical Annual Childhood examination with careful skin and neurologic examination Breast Self Monthly 18 Examination Clinical Breast Twice a year 20‐25 (or 5‐10 years prior to earliest case of breast cancer in the family, whichever comes first) Examination Mammography Annual Age 20‐25 (or 5‐10 years prior to earliest case of breast cancer in family, whichever comes first) and/or breast MRI screening Colonoscopy Every 2‐5 No later than age 25 years Other Considerations: 1. Education regarding signs and symptoms of cancer. 2. Risk‐reducing mastectomy on case‐by‐case basis. 3. Therapeutic radiation therapy for breast cancer should be used with caution. 4. Pediatricians should be apprised of the risk of childhood cancers in affected families. 5. Participation in clinical trials to determine effectiveness of screening modalities, such as PET scan, abdominal ultrasound, and brain MRI. 6. Target surveillance based on individual family histories. 2