Predominance of BRCA2 mutation and estrogen receptor-positive breast cancer among BRCA1/2 mutation carriers. - Archive ouverte HAL Accéder directement au contenu
Poster De Conférence Année : 2022

Predominance of BRCA2 mutation and estrogen receptor-positive breast cancer among BRCA1/2 mutation carriers.

Kevin Yauy
Jean-Pierre Daurès
Clare Turnbull
  • Fonction : Auteur
  • PersonId : 1099983
Kevin S. Hughes
  • Fonction : Auteur
Nicolas Philippe
  • Fonction : Auteur
  • PersonId : 938668

Résumé

551 Background: PARP inhibitor (PARPi) agents can improve progression-free survival of patients with breast cancer (BC) who carry a germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant (gBRCA1/2) in both the metastatic and adjuvant setting. Therefore, we need to redefine the criteria of women and tumor phenotype that should be tested for gBRCA1/2. Methods: We studied the relative distribution of gBRCA1 and gBRCA2 in unselected populations of women with BC and in unaffected individuals. We also analyzed the proportion of estrogen receptor (ER)-positive (ER+) tumors in unselected BC patients with gBRCA1/2.We performed a meta-analysis of studies of unselected BC that analyzed the relative contribution of gBRCA1 versus gBRCA2 and ER+ tumors among gBRCA1/2 carriers. We then performed a meta-analysis of gBRCA1/2 carriage in unaffected individuals, from genome-wide population studies, the gnomAD databank, and case–control studies. Results: The BRCA2 gene was involved in 54% of BC in unselected patients with gBRCA1/2 (n=108,699) and 59% of unaffected individuals (n=238,973) as compared with 38% of gBRCA1/2 family cohorts (n=29,700). The meta-analysis showed that 1.66% (95% CI 1.08-2.54) and 1.71% (95% CI 1.33-2.2) of unselected BC patients carried a gBRCA1 and gBRCA2, respectively. In unaffected individuals, the frequency of heterozygosity for gBRCA1 and gBRCA2 was estimated at 1/434 and 1/288, respectively. Nearly 0.5% of unaffected individuals in the studied populations carried a gBRCA1/2. Carriage of a gBRCA was 2.5% for patients with ER+ tumors (95% CI 1.5-4.1) and 5.7% (95% CI 5.1-6.2) for those with ER- tumors. Overall, 58% of breast tumors occurring in women carrying a gBRCA1/2 were ER+ (n=86,870). Conclusions: This meta-analysis showed that gBRCA2 carriage is predominant in unselected BC and in unaffected individuals. ER+ tumors among women with gBRCA1/2-related BC is predominant and has been underestimated. Because PARPi agents improve progression-free survival with ER+ gBRCA1/2 BC in both the adjuvant and metastatic setting, BC should be considered regardless of ER status for BRCA1/2 screening for therapeutic purposes.

Domaines

Cancer

Dates et versions

hal-04402243 , version 1 (18-01-2024)

Identifiants

Citer

Pascal Pujol, Kevin Yauy, Amandine Coffy, Nicolas Duforet-Frebourg, Sana Gabteni, et al.. Predominance of BRCA2 mutation and estrogen receptor-positive breast cancer among BRCA1/2 mutation carriers.. ASCO Annual Meeting, Jun 2022, En ligne, United States. Journal of Clinical Oncology, 40 (16_suppl), pp.551-551, 2022, ⟨10.1200/JCO.2022.40.16_suppl.551⟩. ⟨hal-04402243⟩
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