Breast cancer is involved in two other hereditary syndromes, for which causative genes have been identified. The Li-Fraumeni syndrome is characterized by childhood sarcoma and early-onset breast cancer, brain tumors, and a variety of other cancers. Most families with Li-Fraumeni syndrome appear to be due to germline mutations in the TP53 gene. TP53 mutations confer a very high risk of breast cancer (approaching 100% by age 50) but are much rarer than BRCA1 or BRCA2 mutations (45,46). Cowden's syndrome is a rare syndrome characterized by hamartomas, multiple hamartomas, thyroid cancer, and mucocutaneous lesions and is due to germline mutations in PTEN (61). The risk of breast cancer associated with Cowden's syndrome has not been well estimated, but it is of the order of 30% to 50% lifetime (47).
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