Tumor suppressor genes and breast cancer

The genetic determinants for most breast cancer cases remain elusive. Howev er, a mutation in a tumor suppressor gene, such as p53, BRCA1, BRCA2, or AT M, has been determined to be one mechanism of breast carcinogenesis. It has been established that inherited mutations in p53, BRCA1, and BRCA2 signifi cantly contribute to breast cancer risk, although the importance of an inhe rited ATM mutation is controversial. Sporadic mutations in p53 are also com mon in breast cancer cells. The precise deficiencies that result from these genetic mutations have yet to be fully described. Although the functions o f these genes are different, they are all involved in the maintenance of ge nomic stability after DNA damage. Mutations that impair the function of the se four genes may adversely affect the manner in which DNA damage is proces sed. It is Likely that the risk of breast cancer development is increased t hrough this mechanism. In this article, we review the relevancy of p53, BRC A1, BRCA2, and ATM mutations to breast cancer development, and review the i n vitro, in vivo, and clinical data exploring the mechanisms by which these mutations affect genomic integrity and DNA damage repair. (C) 1999 Wiley-L iss,Inc.