Hereditary breast cancer: from molecular pathology to tailored therapies

J Clin Pathol. 2008 Oct;61(10):1073-82. doi: 10.1136/jcp.2008.057950. Epub 2008 Aug 4.

Abstract

Hereditary breast cancer accounts for up to 5-10% of all breast carcinomas. Recent studies have demonstrated that mutations in two high-penetrance genes, namely BRCA1 and BRCA2, are responsible for about 16% of the familial risk of breast cancer. Even though subsequent studies have failed to find another high-penetrance breast cancer susceptibility gene, several genes that confer a moderate to low risk of breast cancer development have been identified; moreover, hereditary breast cancer can be part of multiple cancer syndromes. In this review we will focus on the hereditary breast carcinomas caused by mutations in BRCA1, BRCA2, Fanconi anaemia (FANC) genes, CHK2 and ATM tumour suppressor genes. We describe the hallmark histological features of these carcinomas compared with non-hereditary breast cancers and show how an accurate histopathological diagnosis may help improve the identification of patients to be screened for mutations. Finally, novel therapeutic approaches to treat patients with BRCA1 and BRCA2 germ line mutations, including cross-linking agents and PARP inhibitors, are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Cycle Proteins / genetics
  • Checkpoint Kinase 2
  • DNA Repair / genetics
  • DNA-Binding Proteins / genetics
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Humans
  • Protein Serine-Threonine Kinases / genetics
  • Tumor Suppressor Proteins / genetics

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • Checkpoint Kinase 2
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • CHEK2 protein, human
  • Protein Serine-Threonine Kinases