943P - Location of mutation in BRCA2 gene and survival in patients with ovarian cancer

Date 09 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Ovarian Cancer
Gynaecologic Malignancies
Pathology/Molecular Biology
Presenter S.Intidhar Labidi-Galy
Citation Annals of Oncology (2017) 28 (suppl_5): v330-v354. 10.1093/annonc/mdx372
Authors S.I. Labidi-Galy1, T. Olivier1, M. Rodrigues2, D. Ferraioli3, O. Derbel4, A. Bodmer1, P. Petignat5, N. Chopin3, O. Tredan6, P. Heudel6, V. Viassolo1, A. Ayme7, P.O. Chappuis1, M. Stern8, C. Houdayer8, D. Stoppa-Lyonnet8, A. Buisson9, L. Golmard8, V. Bonadona10, I. Ray-Coquard6
  • 1Department Of Oncology, Hôpitaux Universitaires de Genève - HUG, 1211 - Geneva/CH
  • 2Department Of Medical Oncology, Institut Curie, Paris/FR
  • 3Department Of Surgery, Centre Léon Bérard, 69008 - Lyon/FR
  • 4Department Of Oncology, Hôpital prive Jean mermoz, 69008 - Lyon/FR
  • 5Department Of Gynecology, Hôpitaux Universitaires de Genève - HUG, 1211 - Geneva/CH
  • 6Département D'oncologie Médicale Adulte, Centre Léon Bérard, 69008 - Lyon/FR
  • 7Department Of Genetic And Laboratory Medicine, Hôpitaux Universitaires de Genève - HUG, 1211 - Geneva/CH
  • 8Inserm U830, Psl Research University, Institut Curie, Paris/FR
  • 9Division Of Molecular Genetics, Hospices Civiles de Lyon, Lyon/FR
  • 1013unit Of Prevention And Genetic Epidemiology, Umr Cnrs 5558, Centre Léon Bérard, 69008 - Lyon/FR

Abstract

Background

BRCA2 plays a central role in homologous recombination through loading RAD51 on DNA double strand breaks. Among ovarian cancer (OC) patients, carriers of BRCA2 mutations have better survival than BRCA1 carriers and non-carriers. The objective of this study is to determine whether location of mutations in BRCA2 gene impacts survival of OC patients.

Methods

A study cohort of 340 women with OC, who underwent genetic germline testing for BRCA1 and BRCA2 genes and received platinum-based chemotherapy, were identified in four hospitals in Switzerland and France. Duration of follow-up was 4.14 years. The Cancer Genome Atlas (TCGA) cohort of high-grade serous ovarian carcinomas (n = 316) was used as a validation cohort. Progression-free survival (PFS) and overall survival (OS) were analyzed.

Results

In the study cohort, 74 and 78 patients were carriers of germline mutations of BRCA1 and BRCA2, respectively. After adjustment for FIGO stage and macroscopic residual disease, BRCA2 carriers having truncating mutations in the RAD51-binding domain (RAD51-BD; exon 11) have significantly prolonged 5-years PFS (58%; adjusted Hazard ratio [HR], 0.36; 95% CI, 0.20-.64; p=0.001) compared to non-carriers. BRCA2 carriers with mutations located in other domains of the gene have not prolonged 5-years PFS (28%, adjusted HR, 0.67; 95% CI, 0.42-1.07; p=0.094). In the TCGA cohort, after adjustment for FIGO stage and macroscopic residual disease, only BRCA2 carriers harboring germline or somatic mutations in the RAD51-BD had prolonged 5-years PFS (46%; adjusted HR, 0.30; 95% CI, 0.13-0.68; p=0.004) and 5-years OS (78%; adjusted HR, 0.09; 95% CI, 0.02-0.38; p=0.001), compared to non-carriers.

Conclusions

Among patients with ovarian cancer, BRCA2 carriers having mutations located in RAD51-BD (exon 11) have prolonged progression-free survival and overall survival.

Clinical trial identification

Legal entity responsible for the study

S. Intidhar Labidi-Galy

Funding

None

Disclosure

All authors have declared no conflicts of interest.