The genetic basis of breast cancer and its clinical implications.
While it has long been recognized that a proportion of breast cancer cases are the result of an inherited familial predisposition, precise knowledge of the underlying genetic processes has been lacking. Recent advances in molecular biology, however, have shown that hereditary breast cancer may eventuate as a result of mutations on several specific gene loci including BRCA1, BRCA2, ATM gene, PTEN and p53. Several other less frequently occurring predisposition genes such as the androgen receptor gene (AR), the HNPCC genes and the oestrogen receptor gene may also be involved, but to a lesser extent. Overall, approximately 5-10% of all breast cancers are thought to involve one of these inherited predisposition genes, with BRCA1 and BRCA2 being responsible for as much as 90% of this group. Because of the complex nature of genetic testing, mutation analysis is not presently routinely available outside genetic counselling clinics. In this review the current knowledge and role of each predisposition gene is outlined and the management implications of genetic testing for members of breast cancer families for both affected and non-affected members are discussed. The need to provide comprehensive counselling for women with an inherited predisposition to breast cancer has seen the evolution of the familial cancer clinic, involving a multidisciplinary specialist team approach. Familial cancer clinics will provide individuals with information about their risk of developing breast cancer and offer advice regarding further management strategies. It is important that surgeons, who have traditionally played a key role in breast cancer treatment, remain cognizant of these advances in genetic molecular biology, and in so doing continue to remain key participants in the conduct of breast cancer management.
Bennett
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IC
Princess Alexandra Hospital, Brisbane, Australia.
Gattas
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M
Teh
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BT
D048868:Adaptor Proteins, Signal Transducing; D064007:Ataxia Telangiectasia Mutated Proteins; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics* / Q000601:surgery; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005192:Family Health; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008019:Life Style; D008408:Mastectomy; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics; D012306:Risk; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011506:Proteins; D011944:Receptors, Androgen; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000070957:MutL Protein Homolog 1