CLINICAL AND RESEARCH ISSUES IN BREAST-CANCER GENETICS

Breast cancer is the most common form of cancer in women in the U.S. T he risk factors for developing breast cancer include increasing age, a family history of breast cancer, and the lack of a child by age 30. A substantial fraction of breast cancer, however, occurs in women who h ave no identifiable risk factors. The diagnosis, pathology, treatment, and presymptomatic testing of cancer susceptibility genes are reviewe d. Syndromes with an associated risk of breast cancer are described, s uch as hereditary breast-ovarian cancer syndrome, Li-Fraumeni syndrome , ataxia telangiectasia, and Cowden's disease. With the localization o f the BRCA1 gene to chromosome 17q21 and the BRCA2 gene to chromosome 13q12, issues surrounding breast cancer susceptibility genetic testing are assuming an ever greater measure of importance. The sensitivity a nd specificity for molecular testing of cancer susceptibility genes, h owever, have not been well defined. The progress in presymptomatic gen etic testing is further hampered by various factors such as the techni cal difficulty in distinguishing mutations from polymorphisms, the num ber of different mutations identified thus far and the possibility of false positive and false negative results. Laboratory quality assuranc e/duality control issues are of paramount importance to avoid misleadi ng interpretations. Many issues surrounding genetic screening and test ing, such as insurance and employment discrimination, privacy, and inf ormed consent, are under active debate, and guidelines and standards a re under active development. It is therefore important to proceed with caution, so that irreversible harm resulting from data misinterpretat ion can be avoided.