Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session

1884 - Location of mutation in BRCA2 gene and survival in patients with ovarian cancer

Date

09 Sep 2017

Session

Poster display session

Presenters

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

Author affiliations

  • 1 Department Of Oncology, Hôpitaux Universitaires de Genève - HUG, 1211 - Geneva/CH
  • 2 Department Of Medical Oncology, Institut Curie, Paris/FR
  • 3 Department Of Surgery, Centre Léon Bérard, 69008 - Lyon/FR
  • 4 Department Of Oncology, Hôpital prive Jean mermoz, 69008 - Lyon/FR
  • 5 Department Of Gynecology, Hôpitaux Universitaires de Genève - HUG, 1211 - Geneva/CH
  • 6 Département D'oncologie Médicale Adulte, Centre Léon Bérard, 69008 - Lyon/FR
  • 7 Department Of Genetic And Laboratory Medicine, Hôpitaux Universitaires de Genève - HUG, 1211 - Geneva/CH
  • 8 Inserm U830, Psl Research University, Institut Curie, Paris/FR
  • 9 Division Of Molecular Genetics, Hospices Civiles de Lyon, Lyon/FR
  • 10 13unit Of Prevention And Genetic Epidemiology, Umr Cnrs 5558, Centre Léon Bérard, 69008 - Lyon/FR
More

Resources

Abstract 1884

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.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.