Indications for BRCA1 and BRCA2 mutation testing in hereditary breast and ovarian cancer families

Abstract

9720 Background: Since characterization of BRCA1 and BRCA2 in 1994 1995 resp. genetic testing of these genes is possible. Germline mutations in these genes are the most common reason for hereditary breast and ovarian cancer. Methods: Since December 1996 testing of BRCA1 or BRCA2 mutations is implemented in twelve university hospitals all over Germany granted by the German Cancer Aid (Deutsche Krebshilfe). After detailed counseling by a gynecologist, a psycho-oncologist and a human geneticist genetic testing is offered to those family members already laid up with breast or ovarian cancer or those who are on risk for hereditary breast or ovarian cancer. Families are grouped into different risk categories: A=three or more family members suffering from breast cancer with at least two of them becoming deseased premenopausally or male breast cancer, B=families with breast and/or ovarian cancer or more family member having breast and ovarian cancer, C=two family members suffering from breast cancer with at least one of them becoming diseased premenopausally or only one woman with bilateral breast cancer first diseased in an age of ≤ 40 years, D=two and more women suffering from postmenopausal breast cancer and E=only one woman with early onset of breast cancer (≤ 35 years). By now more than 1100 persons have been tested. These are the results of an interim analysis of 2755 (hereof 1077 tested) cancer patients out of 737 families. Results: The distribution of the families in the previously described categories was A=34,5%, B=27,1%, C=27,5%, D=4,3% and E=4,0%. In 44% of all families a mutation in BRCA1 or 2 was found but 56% of all families were found BRCA1/2 negative. Looking to all detecte BRCA1-mutations the major percentage was verified in B-category (53,5%) and the A-category (37,6%) and only 6% in C, 3% E and none in D families. BRCA2-mutations are mostly find in A (57,5%) and B families (26,0%) and less in C (12,3%), D(2,7%) and E families (1,4%). On the other hand 76,8% C, 77,4% D and 82,8% E families were tested BRCA1/2 negativ. Conclusions: According to our results genetic testing is indicated in families with either breast and ovarian cancer or multiple premenopausal breast cancer. No significant financial relationships to disclose.