BRCA1‐related breast cancer in Austrian breast and ovarian cancer families: Specific BRCA1 mutations and pathological characteristics

We identified 17 BRCA1mutations in 86 Austrian breast and ovarian cancer families (20%) that were screened for mutations by denaturing high‐performance liquid chromatography (DHPLC) and the protein truncation test (PTT). Eleven distinct mutations were detected, 4 of them (962del4, 2795del4, 3135del4 and L3376stop) not previously reported in families of non‐Austrian origin. In addition, 6 rare missense mutations (allele frequency < 1%) with unknown biological effects were identified. Four mutations occurred more than once in the Austrian population: 2795del4 (3 times), Cys61Gly (3 times) 5382insC (2 times) and Q1806stop (2 times). Haplotype analysis of the 4 recurrent mutations suggested a common ancestor for each of these. Thirty‐four breast cancer cases from 17 families with BRCA1 mutations were further analyzed. We observed a low median age of onset (39.5 years). Sixty‐eight percent of all BRCA1 breast cancer cases had negative axillary lymph nodes. This group showed a significant prevalence of a negative estrogen and progesterone receptor status and stage I tumors compared with an age‐related, node‐negative control group. The prevalence of grade III tumors was marginally significant . Survival analysis either with a control group matched for age (within 5 years), grade, histologic subtype and estrogen receptor status, or with an age‐related, node‐negative comparison group, showed no statistical difference. Int. J. Cancer 77:354–360, 1998. © 1998 Wiley‐Liss, Inc.