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

Authors

PASCAL PUJOL

Pascal Pujol

CREEC, UMR IRD 224-CNRS 5290 Université Montpellier, Montpellier, France

Pascal Pujol , Kévin Yauy , Amandine Coffy , Nicolas Duforet-Frebourg , Sana Gabteni , Jean-Pierre Daurès , Frederique Madeleine Penault-Llorca , Laetitia Collet , Frédéric Thomas , Clare Turnbull , Virginie Galibert , Chloé Rideau , Benoit You , David Geneviève , Kevin S. Hughes , Nicolas Philippe

Organizations

CREEC, UMR IRD 224-CNRS 5290 Université Montpellier, Montpellier, France, SeqOne Genomics, Montpellier, France, LMNT-AESIO Santé, Montpellier, France, CHU Montpellier, Montpellier, France, Centre Jean Perrin, Clermont-Ferrand, France, Centre Léon Bérard, Lyon, France, The Institute of Cancer Research, London, United Kingdom, Centre Hospitalier Universitaire Montpellier, Montpellier, France, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), Lyon, France, INSERM U1183, Montpellier, France, Massachusetts General Hospital, Boston, MA

Research Funding

No funding received

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.

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Breast Cancer—Local/Regional/Adjuvant

Track

Breast Cancer

Sub Track

Biologic Correlates

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr 551)

DOI

10.1200/JCO.2022.40.16_suppl.551

Abstract #

551

Poster Bd #

323

Abstract Disclosures