Abstract 578P
Background
Good prognosis has been accepted in patients with BRCA mutations associated-Epithelial Ovarian Cancer (EOC), but there are a group with primary resistance to platinum chemotherapy and bad prognosis. BRCA mutations may be a large rearrangement or punctual. In mexican population a large deletion of exons 9 to 12 in BRCA1 has a founder effect.
Methods
We included 109 women with a diagnosis of EOC between 2015 and 2019. Patients received surgery and standard chemotehrapy and the genetic testing was done by next-generation sequencing (NGS) and microarray analysis test of BRCA1/2 genes. The pathogenic variants (PVs) were divided according to their location in the susceptibility region in both genes.
Results
109 patients 77.1% BRCA - and 22.9% had a clear PV: BRCA+ cases. Fourteen different PVs were found in our population, 84% involved BRCA1 and 16% BRCA2. The Mexican founder deletion was identified in 42% of all BRCA1+ cases, the rest were punctual variants or microdeletions in BRCA 1 or 2 genes. PVs were found in Ovarian Cancer Cluster Region (OCCR) 69%, and in Breast Cancer Cluster Region (BCCR) 27%, only one case had a PV outside of both regions (case 3: c.496del in BRCA1). Hereditary Breast -Ovarian Cancer (HBOC) syndrome was diagnosed in 66% of patients with the founder deletion, in 75% of BRCA1 with other PV, 100% in the BRCA2 group and none in BRCA- patients. The BRCAness phenotype was found in 13 patients in BRCA- group. There were no differences between the presence of HBOC syndrome, clinical stage at diagnosis, histology or overall survival (OS). Progression free-survival was 32 mo (BRCA-), 13 mo (BRCA+), 12 mo (BRCA1+), 13 mo (BRCA2+), 12 mo (founder mut), 9 mo (no founder mut) P=0.003 and resistance of platinum therapy was 20%, 32% , 25%, 65 and 36% in each one group.
Conclusions
Different pathogenic variant in BRCA genes have been identified in EOC. In general, in our population ovarian cancer associated to BRCA mutation has worse prognosis than sporadic ovarian cancer (BRCA negative). In the other hand, the cases with the large deletion in exons 9-12 in BRCA1 gene has almost the double risk of primary resistance to platinum treatment versus any other pathogenic variant.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Gomez-Garcia Eva María.
Funding
BRCA test were founding by AstraZeneca Mexico, and the traduction of the complete study.
Disclosure
L. Lechuga-Becerra: Non-Financial Interests, Institutional, Leadership Role: AstraZeneca Mexico. All other authors have declared no conflicts of interest.