Predominance of BRCA2 mutation and estrogen receptor-positive breast cancer among BRCA1/2 mutation carriers
| العنوان: | Predominance of BRCA2 mutation and estrogen receptor-positive breast cancer among BRCA1/2 mutation carriers |
|---|---|
| المؤلفون: | Pascal Pujol, Kévin Yauy, Amandine Coffy, Nicolas Duforet-Frebourg, Sana Gabteni, Jean-Pierre Daurès, Frédérique Penault-Llorca, Frédéric Thomas, Kevin Hughes, Clare Turnbull, Virginie Galibert, Chloé Rideau, Laetitia Collet, Benoit You, David Geneviève, Nicolas Philippe |
| المصدر: | Journal of Clinical Oncology. 40:551-551 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Oncology |
| الوصف: | 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. Objective: 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.Design: 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. Overall, 58% of breast tumors occurring in women carrying a gBRCA1/2 were ER+ (n=86,870).Conclusion: 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. |
| تدمد: | 1527-7755 0732-183X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::717527490d66e879bf61ee820bb837bd https://doi.org/10.1200/jco.2022.40.16_suppl.551 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....717527490d66e879bf61ee820bb837bd |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
|---|