Testing for hereditary breast and ovarian cancer in the southeastern United States

Objectives To detail characterization of mutations and uncharacterized variants in the breast cancer susceptibility genes BRCA1 and BRCA2, as observed in a popul ation of breast cancer patients from the southeastern United States, and to examine baseline characteristics of women referred for counseling and test ing and provide a preliminary look at how counseling and testing affected i ntentions toward prophylactic surgery, Background Mutations in the BRCA1 and BRCA2 genes give rise to a dramatically increase d risk of developing breast or ovarian cancer or both. There are many repor ts about special populations in which deleterious mutations are present ata high frequency. it is useful to study these genes in more heterogeneous po pulations, reflecting different geographic regions. Interest in preventive surgery for gene carriers is high in women and their surgeons. Methods Women were recruited through a prospective clinical trial of counseling and free genetic testing. BRCA1 and BRCA2 were screened for mutations using st andard techniques, and results were given to participants. Baseline questio nnaires determined interest in preventive surgery at the beginning of the s tudy. Follow-up questionnaires for those who completed testing surveyed int erest in prophylactic surgery after counseling and receiving test results, Results OC 213 women who completed counseling and testing, 44 (20.6%) had 29 separa te mutations; there were II Jewish women carrying three founder mutations. Twenty-eight women (13.1%) had uncharacterized variants in BRCA1 or BRCA2; nine were not previously reported. Women overestimated their chances of pos sessing a deleterious gene mutation compared to a statistical estimate of c arrier risk, A number of women changed their intentions toward preventive s urgery after genetic counseling and testing, Conclusions Hereditary breast cancer due to mutations in BRCA1 and BRCA2 was a heteroge neous syndrome in the southeastern United States. Most mutations were seen just once, and uncharacterized variants were common and of uncertain clinic al significance. in general, positive test results tended to reinforce inte ntions toward prophylactic surgery. in contrast, women not interested in su rgery at the time of entry tended to remain reluctant after testing and cou nseling.