Medical guidelines for Li–Fraumeni syndrome 2019, version 1.1
Authors: Kumamoto Tadashi , Yamazaki Fumito , Nakano Yoshiko , Tamura Chieko , Tashiro Shimon , Hattori Hiroyoshi , Nakagawara Akira , Tsunematsu Yukiko 
Published: October 2021

AbstractLi–Fraumeni syndrome (LFS) is a hereditary tumor that exhibits autosomal dominant inheritance. LFS develops in individuals with a pathogenic germline variant of the cancer-suppressor gene,TP53(individuals withTP53pathogenic variant). The number of individuals withTP53pathogenic variant among the general population is said to be 1 in 500 to 20,000. Meanwhile, it is found in 1.6% (median value, range of 0–6.7%) of patients with pediatric cancer and 0.2% of adult patients with cancer. LFS is diagnosed by the presence of germlineTP53pathogenic variants. However, patients can still be diagnosed with LFS even in the absence of aTP53pathogenic variant if the familial history of cancers fit the classic LFS diagnostic criteria. It is recommended thatTP53genetic testing be promptly performed if LFS is suspected. Chompret criteria are widely used for theTP53genetic test. However, as there are a certain number of cases of LFS that do not fit the criteria, if LFS is suspected,TP53genetic testing should be performed regardless of the criteria. The probability of individuals withTP53pathogenic variant developing cancer in their lifetime (penetrance) is 75% for men and almost 100% for women. The LFS core tumors (breast cancer, osteosarcoma, soft tissue sarcoma, brain tumor, and adrenocortical cancer) constitute the majority of cases; however, various types of cancers, such as hematological malignancy, epithelial cancer, and pediatric cancers, such as neuroblastoma, can also develop. Furthermore, approximately half of the cases develop simultaneous or metachronous multiple cancers. The types ofTP53pathogenic variants and factors that modify the functions ofTP53have an impact on the clinical presentation, although there are currently no definitive findings. There is currently no cancer preventive agent for individuals withTP53pathogenic variant. Surgical treatments, such as risk-reducing bilateral mastectomy warrant further investigation. Theoretically, exposure to radiation could induce the onset of secondary cancer; therefore, imaging and treatments that use radiation should be avoided as much as possible. As a method to follow-up LFS, routine cancer surveillance comprising whole-body MRI scan, brain MRI scan, breast MRI scan, and abdominal ultrasonography (US) should be performed immediately after the diagnosis. However, the effectiveness of this surveillance is unknown, and there are problems, such as adverse events associated with a high rate of false positives, overdiagnosis, and sedation used during imaging as well as negative psychological impact. The detection rate of cancer through cancer surveillance is extremely high. Many cases are detected at an early stage, and treatments are low intensity; thus, cancer surveillance could contribute to an improvement in QOL, or at least, a reduction in complications associated with treatment. With the widespread use of genomic medicine, the diagnosis of LFS is unavoidable, and a comprehensive medical care system for LFS is necessary. Therefore, clinical trials that verify the feasibility and effectiveness of the program, comprising LFS registry, genetic counseling, and cancer surveillance, need to be prepared.