Hereditary breast cancer: new genetic developments, new therapeutic avenues

• Published in: Human genetics Vol. 124; no. 1; pp. 31 - 42
• Main Authors: Campeau, Philippe M., Foulkes, William D., Tischkowitz, Marc D.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.08.2008; Springer; Springer Nature B.V
• Subjects: Acid Anhydride Hydrolases; AMP-Activated Protein Kinase Kinases; Animals; Antigens, CD; Ataxia Telangiectasia Mutated Proteins; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - therapy; Cadherins - genetics; Cadherins - physiology; Cancer; Cell Cycle Proteins - genetics; Cell Cycle Proteins - physiology; Checkpoint Kinase 2; Classical genetics, quantitative genetics, hybrids; Development and progression; Disease susceptibility; DNA repair; DNA Repair Enzymes - genetics; DNA Repair Enzymes - physiology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Fanconi Anemia Complementation Group N Protein; Fanconi Anemia Complementation Group Proteins; Fundamental and applied biological sciences. Psychology; Gene Function; Genes; Genes, BRCA1 - physiology; Genes, BRCA2 - physiology; Genes, p53 - physiology; Genetic aspects; Genetic research; Genetics of eukaryotes. Biological and molecular evolution; Genetics, Medical - trends; Genomes; Genomics; Gynecology. Andrology. Obstetrics; Health aspects; Human; Human Genetics; Humans; Mammary gland diseases; Medical sciences; Metabolic Diseases; Molecular Medicine; Monosaccharides; Nuclear Proteins - genetics; Nuclear Proteins - physiology; Oncology, Experimental; Penetrance; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - physiology; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - physiology; Review Article; RNA Helicases - genetics; RNA Helicases - physiology; Sugars; Therapeutics - trends; Tumor proteins; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - physiology; Tumors; Fanconi Anemia; Breast Cancer Susceptibility; Breast Cancer; Hereditary Breast Cancer; Nijmegen Breakage Syndrome; Mammary gland diseases; Breast disease; Development; Genetics; Breast cancer; Malignant tumor; Hereditary; Cancer
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s00439-008-0529-1

Six genes confer a high risk for developing breast cancer ( BRCA1/2 , TP53 , PTEN , STK11 , CDH1 ). Both BRCA1 and BRCA2 have DNA repair functions, and BRCA1/2 deficient tumors are now being targeted by poly(ADP-ribose) polymerase inhibitors. Other genes conferring an increased risk for breast cancer include ATM , CHEK2 , PALB2, BRIP1 and genome-wide association studies have identified lower penetrance alleles including FGFR2 , a minor allele of which is associated with breast cancer. We review recent findings related to the function of some of these genes, and discuss how they can be targeted by various drugs. Gaining deeper insights in breast cancer susceptibility will improve our ability to identify those families at increased risk and permit the development of new and more specific therapeutic approaches.