Different expression of BRCA1 status and clinical variables in a sample of Italian women with early onset breast cancer (EOBC)

Abstract

9670 Background: to estimate the spectrum of genetic alteration, family history (FH) and clinical variables in a EOBC population, diagnosed before 41 yrs, consecutively seen at the Genetic Oncology Service of the Parma Hospital from 1999 to 2003, and to investigate the contribution of BRCA1/2 germline mutation to the phenotype of these tumors. Methods: we analyzed clinical and pathological characteristics of 60 EOBC pts. All women underwent full genetic counseling. Of these, 52 (86%) were tested for BRCA1 and BRCA2 mutation analysis while 8 (14%) pts refused it. Exon 11 was screened for BRCA1 mutations using Protein Truncation test (PTT); mutations detected by PTT were confirmed by Direct Sequencing (DS). All the other exons were analyzed by DS. BRCA2 gene was screened using Denaturing High Performance Liquid Chromatography (DHPLC) for all coding exons. Samples showing a heterozygous DHPLC elution profile were subsequently analyzed by DS. Results: 33 (55%) and 10 (16%) out of the 60 pts had breast and ovarian cancer FH, respectively. Median age of BC diagnosis was 34 yrs (range: 23–41); 7 pts (13%) had Bilateral Breast Cancer (BBC). Two pts had similar history of sarcoma at 11–12 years and EOBC at 31–32 years and one patient had EOBC + Ovarian cancer + Malignant Melanoma. Of the 19 pts with completed mutation analysis, 14 (74%) had wild-type BRCA1(WT) (including 3 pts with EOBC+other tumors), 3 (16%) had variants of unclear significance, 2 (10%) had deleterious mutations in BRCA1. Breast FH was similarly distributed in the 5 mutation carriers (MC) and in the 14 WT (60% vs 78%), while ovarian FH was more frequent in MC (60% vs 21%). One of 5 MC had BBC (age 28 and 42) and 1 had no FH. Stage II-III (80% vs 36%), grade 3 (75 % vs 33%), lack of estrogen (50% vs 20%) and progesterone receptor (67% vs 20%), and high proliferation rate (75% vs 43%) were more common in MC than in WT. BRCA2 analysis is still ongoing. Until now, a deleterious mutation in BRCA2 gene was detected in two pts. Conclusion: our data confirm that in EOBC adverse histopathologic features and ovarian FH are more predictive of being MC than good histopathologic features and breast FH. No significant financial relationships to disclose.