It is important to bear in mind that not all families with a pedigree suggestive of hereditary breast cancer are linked to BRCA1 or BRCA2. Alterations in other genes, such as P53 (Li-Fraumeni syndrome) and PTEN (Cowden’s syndrome) may account for a proportion of such families (Table 11.2). These additional syndromes are quite rare. Most families with an apparent predisposition to breast cancer that cannot be attributed to either BRCA1 or BRCA2 remain unexplained.
The Li-Fraumeni syndrome (LFS) is characterized by the occurrence of multiple different tumor types within a kindred, often arising at very early ages. The syndrome is most commonly attributable to germline mutations n P53. Soft-tissue sarcoma and osteosarcoma, adrenocortical carcinoma, brain tumors and leukemias are the tumors most often associated with LFS, but early-onset breast cancer is actually one of the most common component tumors.
Cowden’s syndrome (also known as Cowden disease) is associated in at east some families with germline mutations of PTEN. The original syndrome was characterized by the presence of multiple hamartomatous lesions, papillomas of the lip and tongue and acral keratoses. An increased risk of early-onset breast cancer (and also thyroid cancer) has been reported to be associated with the syndrome.
Several other conditions have been reported to be associated with an ncreased risk of breast cancer. These include the Muir-Torre syndrome and the Peutz-Jegher syndrome, both of which are more commonly associated with gastrointestinal tumors. Rare associations have been described with a constitutional translocation of chromosomes 11 and 22, as well as with alterations in the androgen-receptor gene. Finally, there have been reports that the carrier state for ataxia telangiectasia, an autosomal recessive neuroogic disorder caused by mutations in the gene ATM, is associated with an ncreased breast cancer risk.
Mark E. Robson
Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations. J Natl Cancer Inst 2003