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Naoto SHIKAMA3), Mayumi UENO4), Mitsue SAITO1), Masami ARAI1, 5)1)Department of Breast Oncology, Juntendo University Graduate School of Medicine, Tokyo, Japan2)Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo, Japan4)Ogurihara Clinic, Masamakai Medical Corporation, Tokyo, Japan3)Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan5)Department of Clinical Genetics, Juntendo University Graduate School of Medicine, Tokyo, JapanRitsuko SASAKI1), Yoshiya HORIMOTO1, 2), Harumi SAEKI2), Shoji SATO3), Katsuhiro SANO3), Corresponding author: Masami AraiDepartment of Clinical Genetics, Juntendo University Graduate School of Medicine2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, JapanTEL: +81-3-3813-3111　E-mail: ms-arai@juntendo.ac.jp〔Received　Mar. 24, 2022〕〔Accepted　May. 31, 2022〕J-STAGE Advance published date: Aug. 2, 2022Copyright © 2022 The Juntendo Medical Society. This is an open access article distributed under the terms of Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original source is properly credited. doi: 10.14789/jmj.JMJ22-0012-CR　We herein present the case of a 33-year-old woman with no family history of metachronous bilateral breast cancer and osteosarcoma, diagnosed with Li-Fraumeni syndrome (LFS), which is a rare autosomal dominant hereditary cancer syndrome associated with a germline TP53 variant. She was diagnosed with left distal femoral osteosarcoma at the age of 16, and metachronous bilateral breast cancer at the ages of 29 and 33. When the third cancer was diagnosed, a hereditary tumor syndrome was suspected and the patient was referred to our genetic outpatient clinic. There was no family history of the ‘core’ cancers for LFS, but since the patient met Chompret’s criteria, germline TP53 genetic testing was performed with the patient’s will. A pathogenic variant, TP53:c.216dupC (p.Val73ArgfsX76) was found in exon 4 of the gene. This case is didactic because radiotherapy was performed on the first breast cancer before the diagnosis of LFS was made; radiation should be avoided if there are other options in LFS because of the inability to repair DNA damage. As a lesson learned, oncologists reaffirmed the importance of being aware of hereditary tumors from the keywords “multiple,” “young,” “familial,” and “rare,” and consulting the genetic department. In addition, surveillance using whole-body magnetic resonance imaging is recommended in LFS. However, this system is not yet provided nationwide, but we have newly settled it in our hospital.Juntendo Medical Journal2022. 68(4), 405-412Key words: Li-Fraumeni syndrome, hereditary cancer syndrome, treatment management, surveillance, whole-body MRICase ReportsLFS-Related Breast Cancer Treatment Strategy and Establishment of a Surveillance SystemIntroductionLi-Fraumeni syndrome (LFS) is a rare auto-somal dominant hereditary cancer syndrome asso-ciated with germline TP53 pathogenic or likely pathogenic variants1). The tumor suppressor gene, TP53, is located on chromosome 17, and the protein product of TP53 is localized in a cell nucleus and binds directly to DNA. It has been called the “guardian of the genome” and plays important roles in controlling the cell cycle and apoptosis2). The frequency of germline TP53 variants in the general population has been reported to be about 1.6% in pediatric cancer patients3, 4) and about 0.2% in adult cancer patients5). The penetrance of germline TP53 variants is 75% in males and almost 100% in females6). Regarding age of cancer onset, an anal-ysis of 415 individuals with TP53 pathogenic variant in 214 French families with LFS showed that the cancer penetrance for young people aged 0, 5, and 18 years were 4%, 22%, and 41%, respectively6). Furthermore, an analysis by the US National Cancer 405Lessons Learned in Practice with Li-Fraumeni Syndrome: