Sporadic breast cancer in young women: prevalence of loss of heterozygosity at p53, BRCA1 and BRCA2.

Abstract

Previous studies have shown that breast cancers have more aggressive pathologic features in young women. In order to examine genetic alterations associated with early-onset breast cancer, 31 patients with no known family history, aged 26-35 years at diagnosis, were examined for loss of heterozygosity (LOH) at 3 key chromosomal intervals: 17p (p53), 17q 21 (BRCA1) and 13q12-13 (BRCA2) using polymerase chain reaction analysis of polymorphic microsatellite markers. These were compared with 31 patients aged 55-72 years that were matched for size, type and grade. All young breast cancer cases exhibited LOH for at least 1 marker and 20 cases (64.5%) exhibited LOH at 1 or more markers from each interval. The frequency of LOH detected for each of the markers was as follows 17p: p534N (33.3%), D17S796 (36.7%), D17S799 (63.3%) and D17S513 (59.3%); 17q: D17S855 (64.5%), THRA1 (46.7%) and D17S579 (33.3%); and 13q: D13S260 (74.2%), D13S171 (47.6%) and D13S267 (40.0%). These frequencies are higher than those observed at the 3 markers studied in the matched postmenopausal patients: D17S799 (41.4%), D17S855 (35.5%), D13S260 (30.0%). These differences in frequency of LOH were statistically significant for the D17S855 and D13S260 markers (p < 0.025 and p < 0.001 respectively). Although there were more grade III carcinomas (21 of 31 cases), there was no correlation between number of alterations and high grade in younger cases. These data suggest that LOH at these regions could be related to early-onset sporadic breast cancer.