BRCA-ASSOCIATED BREAST-CANCER - ABSENCE OF A CHARACTERISTIC IMMUNOPHENOTYPE

To characterize the biological features of breast cancer associated wi th germ-line mutations in BRCA1 and BRCA2, invasive tumors were studie d from 58 Jewish women ascertained through studies of early-onset brea st cancer. All women were tested for the BRCA1 founder mutations 187de lAG (commonly known as 185delAG) and 5385insC (commonly known as 5382i nsC) and the BRCA2 founder mutation 6174delT. Mutations were detected in 17 of 58 (29.3q) women. Comparing BRCA-associated breast cancers (B ABCs) to cases arising in women without founder mutations, no differen ces were noted in tumor size, tumor stage, or frequency of axillary no dal involvement. Infiltrating ductal carcinoma was the predominant his tological type in both groups, BABCs were significantly more likely to be of histological grade III (100 versus 63%; P = 0.04), estrogen rec eptor negative (75 versus 35%; P = 0.004), and HER2/neu negative (87 v ersus 58%; p = 0.04). An associated intraductal component was present in 59% of BABCs and 76% of cancers not associated with mutations (P = not significant). A high Ki-67 labeling index was more commonly observ ed in BABCs than in cases without mutations (83 versus 48%; P = 0.09). There were no differences between the two groups in the frequency of expression of epidermal growth factor receptor, cathepsin D, bcl-2, p2 7, p53, or cyclin D. There were no significant differences in relapse- free or overall survival. These observations suggest that breast cance rs arising in Jewish women with germ-line BRCA founder mutations have a greater proliferative potential than cancers in women without such m utations. Additional studies of BABC are required to determine the nat ure and implications of additional genetic abnormalities occurring in these tumors.