Biophenotypes and survival of BRCA1 and TP53 deleted breast cancer in young women

The aim of this study was to examine the loss of heterozygosity (LOH) of BR CA1 (17q21) and TP53 (17p13.1) in early-onset breast cancer patients; to co rrelate biopathological characteristics with molecular alterations; and to investigate the survival of LOH-related cancers.BRCA1 and TP53 LOH were eva luated in 78 early-onset breast cancers (less than or equal to 40 years, Gr oup 1) and 80 patients with age < 55 years (Group 2). Cases were characteri zed for multiple biological markers (ER, PR, proliferation index (PI), NEU and p53). LOH was carried out on microdissected paraffin embedded tissues; microsatellites D17S855 (BRCA1) and D17S786 (TP53) were amplified by fluore scent PCR and analyzed by an automated DNA sequencer. Early-onset breast ca ncers showed a higher frequency of ductal histotype (89,7% vs. 56,3% p < 0. 001), node-positive (53,8% vs. 38,7%), larger size (p = 0.017), higher mito tic rate (p = 0.025), higher nuclear and final grade (p = 0.01 and p = 0.00 1, respectively). D17S855 LOH was 32,8% in group 1 vs. 21% in group 2; D17S 786 LOH was 50,7% vs. 31.3% (p = 0.03), respectively. BRCA1 LOH was correla ted with higher PI (p = 0.032) and higher p53 expression (p < 0.001) in gro up 1 and with higher NEU expression (p = 0.028) in group 2. TP53 LOH was co rrelated with p53 overexpression (p = 0.03) in group 1. A worse clinical ou tcome in early-onset LOH related cancers emerged from follow-up data: TP53 and BRCA1 LOH were associated with a shorter relapse free interval (RFI) (p = 0.03) and a poorer overall survival (OS) (p = 0.04), respectively. This study underlines different biological profiles in the two age groups invest igated, probably reflecting different mechanisms of carcinogenesis. In acco rdance with adverse histopathological features in early-onset patients, LOH -related cancers have an unfavorable prognosis.