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Genetic predisposition to breast cancer: a surgical perspective
1Department of Surgery, 251 Hellenic Air Force Hospital, Messogion and Katehaki, Athens 115 25, Greece.
Background:
Molecular alterations in proto-oncogenes, tumour suppressor genes, and genes that function in DNA damage recognition and repair are considered to be hallmarks of a carcinogenic process, including breast carcinogenesis.
Methods:
A computer-assisted search of the English literature (Medline database, 1990-1999) was performed, followed by a manual search of the reference list of pertinent articles retrieved.
Results:
Hereditary breast cancer accounts for 5-10 per cent of all breast cancer cases. About 90 per cent of hereditary breast cancers involve mutation of the BRCA1 and/or BRCA2 genes. Other cancer-related genes (including myc, c-erbB2, Tsg101 and Mdgi) are involved in breast carcinogenesis, but they do not give rise to familial breast cancer syndromes. Risk estimation is the most important clinical implication. Management options for the high-risk mutation carriers include cancer surveillance and preventive strategies (prophylactic surgery or chemoprevention).
Conclusion:
Despite inadequate knowledge about the genetic predisposition to breast cancer and its clinical implications, the demand for genetic testing is likely to expand rapidly. In addition to risk estimation, cancer surveillance and preventive strategies, gene therapy offers a new and theoretically attractive approach to breast cancer management.