Hereditary breast cancer: new genetic developments, new therapeutic avenues.
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.
Campeau
Philippe M
PM
Department of Medical Genetics, McGill University Health Centre, McGill University, Montreal, QC, Canada. philippe.campeau@mail.mcgill.ca
Foulkes
William D
WD
Tischkowitz
Marc D
MD
D000091162:AMP-Activated Protein Kinase Kinases; D017766:Acid Anhydride Hydrolases; D000818:Animals; D015703:Antigens, CD; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000235:genetics* / Q000628:therapy*; D015820:Cadherins / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D064447:Checkpoint Kinase 2; D045643:DNA Repair Enzymes / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D000076164:Fanconi Anemia Complementation Group N Protein; D051856:Fanconi Anemia Complementation Group Proteins; D019398:Genes, BRCA1 / Q000502:physiology; D024522:Genes, BRCA2 / Q000502:physiology; D016158:Genes, p53 / Q000502:physiology; D005826:Genetics, Medical / Q000639:trends; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000502:physiology; D019683:Penetrance; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D020365:RNA Helicases / Q000235:genetics / Q000502:physiology; D013812:Therapeutics / Q000639:trends; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D000076164:Fanconi Anemia Complementation Group N Protein; D051856:Fanconi Anemia Complementation Group Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins; D064447:Checkpoint Kinase 2; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; C000618935:BRIP1 protein, human; D020365:RNA Helicases; D045643:DNA Repair Enzymes