Abstract P2-12-02: Characteristics of the BRCA mutation profile of a population of patients with triple negative breast cancer
Authors: E Luporsi, M Bronner, A Lesur, D Saint-Dizier, J Sokolowska, L Mansuy, P Jonveaux
Journal: Cancer Research (2013)

Abstract Purpose: This study assessed the relation between age, family history (breast and/or ovarian cancer) and BRCA1 and BRCA2 mutations prevalence in a cohort of patients with triple-negative breast cancer (BC). Methods: We identified in our database 218 patients (pts) with triple negative (TN) breast carcinoma (defined as &amp;lt;1% estrogen and progesterone and HER-2 not over expressed). All pts gave consent for BRCA1 and BRCA2 screening (HRM/sequencing of exons and intron-exon junctions and large rearrangement analysis). In this cohort, we noted family history of breast only, ovarian only or both breast and ovarian cancer. We compared this cohort to 498 pts with a family history of breast cancer (non triple-negative tumors) and/or ovarian cancer that were also screened for BRCA1/2 mutations. Results: In the TN cohort, 146 tests were realized, 72 are still on going. We identified 31 deleterious mutations (21.2%) in BRCA1 and 3 (2.1%) in BRCA2. In 100 cases (68.5%), we found no BRCA mutations and in 13 cases, we found Variants of Unknown Signification (VUS) (8.9%) (5 (3.4%) in BRCA1 and 8 (5.5%) in BRCA2). Concerning family history, 74 pts belonged to families with a history of breast cancer only, 3 pts to families with ovarian cancer only and 10 pts to families with both breast and ovarian cancer. Fifty nine pts were screened on the basis of a TN tumor at age ≤ 50 years old with no other family history of breast or ovarian cancer. The mean age at first diagnosis for all the TN cohort tested is 45.4 ± 10.2 (min 26 - max 76). The mean age of patients for whom a mutation was identified is : 40.6 ± 8.7 for BRCA1 (min 29 - max 69), 45.7 ± 8.5 for BRCA2 (min 37 - max 54). The mean age of patients for whom no BRCA mutation was identified is 46.8 ±10.2 (min 26 - max 76). All patients studied were symptomatic. In the “control cohort”, we identified 26 deleterious mutations (5.2%) in BRCA1 and 28 (5.6%) in BRCA2. In 408 cases (81.9%), we found no BRCA mutations and in 36 cases, we found Variants of Unknown Signification (VUS) (7.2%) (8 (1.6%) in BRCA1 and 28 (5.6%) in BRCA2). We have in our region (Lorraine), a recurrent BRCA1 mutation with founder-effect (c.3481_3491del11 p.Glu1161Phe), the prevalence of which we evaluated in both cohorts. Conclusions: Among the TN cohort, mean age for BRCA1 mutation is lower than for BRCA2 (40.6 ± 8.7 vs 45.7 ± 8.5, non-significant results). By comparing BRCA mutation frequency between the 2 cohorts, we could conclude that: - BRCA mutations are more frequent in the TN cohort : 23.3% vs 10.8% (p = 0.035) - Among these, there are more BRCA1 mutations in the TN cohort : 21.2% vs 5.2% and less BRCA2 mutations : 2.1% vs 5.6% (p = 0.02) Moreover, according to our preliminary results, this particular mutation seems to be more represented among the mutations of the TN cohort (3.5 folds) but we still have to test its impact concerning TN tumors. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-12-02.