been proposed—a proband who has: A tumor belonging to LFS tumor spectrum (e.g., premenopausal breast cancer, soft tissue sarcoma, osteosarcoma, CNS tumor, adrenocortical carcinoma) before age 46 years, and at least one first- or second-degree relative with LFS tumor (except breast cancer if the proband has breast cancer) before age 56 years or with multiple tumors at any age Multiple tumors (except multiple breast tumors), two of which belong to LFS spectrum with the initial cancer occurring before the age of 46 years An adrenocortical carcinoma, choroid plexus tumor, or rhabdomyosarcoma of embryonal anaplastic subtype, at any age of onset, irrespective of family history Breast cancer before age 31 Recommendations Recommendations for individuals from families affected by the syndrome include: Avoidance of radiation therapy to reduce risk of secondary radiation-induced malignancies Children and adults undergo comprehensive annual physical examination Women undergo age-specific breast cancer monitoring beginning at age 25 years All patients consult a physician promptly for evaluation of lingering symptoms and illnesses Suggestions Adults should undergo routine screening for colorectal cancer beginning no later than age 25 years. Individuals should undergo organ-targeted surveillance based on the pattern of cancer observed in their families. Prophylactic mastectomy to reduce the risk of breast cancer is an option. Epidemiology Li–Fraumeni syndrome (LFS) is rare; as of 2011, cases had been reported in more than 500 families. The syndrome was discovered using an epidemiological approach. Li and Fraumeni identified four families in which siblings or cousins of rhabdomyosarcoma patients had a childhood sarcoma, which suggested a familial cancer syndrome. Identification of TP53s the gene affected by mutation was suggested by the same approach. Over half of the cancers in LFS families had been previously associated with inactivating mutations of the p53 gene and in one primary research study, DNA sequencing in samples taken from five Li–Fraumeni syndrome families showed autosomal dominant inheritance of a mutated TP53 gene. See also OSLAM syndrome References Further reading Li–Fraumeni Syndrome by Katherine Schneider, MPH, Kristin Zelley, MS, Kim E Nichols, MD and Judy Garber, MD, MPH, in GeneReviews, a section of GeneTests, published online by the University of Washington with funds from the National Institutes of Health Li–Fraumeni syndrome, in the National Library of Medicine Li–Fraumeni syndrome; LFS1, entry in Online Mendelian Inheritance in Man (OMIM), published by Johns Hopkins University and the National Institutes of Health Cancer DNA replication and repair-deficiency disorders Hereditary cancers Rare diseases