Predominance of BRCA2 Mutation and Estrogen Receptor Positivity in Unselected Breast Cancer with BRCA1 or BRCA2 Mutation.

Autor: Pujol P; Department of Cancer Genetics, CHU Montpellier, Université de Montpellier, 34000 Montpellier, France.; CREEC, UMR IRD 224-CNRS 5290 Université Montpellier, 34000 Montpellier, France., Yauy K; SeqOne Genomics, 34000 Montpellier, France.; Centre de recherche UGA, Institute of Advanced Biosciences, Inserm U 1209, CNRS UMR 5309, 38000 Grenoble, France., Coffy A; Unité de Recherche Clinique LMNT-AESIO Santé, 34000 Montpellier, France., Duforet-Frebourg N; SeqOne Genomics, 34000 Montpellier, France., Gabteni S; Department of Cancer Genetics, CHU Montpellier, Université de Montpellier, 34000 Montpellier, France., Daurès JP; Unité de Recherche Clinique LMNT-AESIO Santé, 34000 Montpellier, France., Penault Llorca F; INSERM U1240, Centre Jean Perrin, Department of BioPathology, University Clermont Auvergne, 63000 Clermont-Ferrand, France., Thomas F; CREEC, UMR IRD 224-CNRS 5290 Université Montpellier, 34000 Montpellier, France., Hughes K; Division of Surgical Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA., Turnbull C; Institute of Cancer Research, 15 Cotswold Rd, London SM2 5NG, UK., Galibert V; Department of Cancer Genetics, CHU Montpellier, Université de Montpellier, 34000 Montpellier, France., Rideau C; Department of Cancer Genetics, CHU Montpellier, Université de Montpellier, 34000 Montpellier, France., Corsini C; Department of Cancer Genetics, CHU Montpellier, Université de Montpellier, 34000 Montpellier, France., Collet L; Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), Faculté de Médecine Lyon-Sud, Université Claude Bernard Lyon 1, 69002 Lyon, France., You B; Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), Faculté de Médecine Lyon-Sud, Université Claude Bernard Lyon 1, 69002 Lyon, France., Geneviève D; Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée, CHU Montpellier, Université de Montpellier, 34000 Montpellier, France.; INSERM U1183, Université de Montpellier, 34000 Montpellier, France., Philippe N; SeqOne Genomics, 34000 Montpellier, France.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2022 Jul 04; Vol. 14 (13). Date of Electronic Publication: 2022 Jul 04.
DOI: 10.3390/cancers14133266
Abstrakt: Background: Poly(ADP-ribose) polymerase 1 inhibitor (PARPi) agents can improve progression-free survival of patients with breast cancer who carry a germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant (gBRCA) in both the metastatic and adjuvant setting. Therefore, we need to reassess the frequency of gBRCA1 and gBRCA2 in order to redefine the criteria for women and tumor phenotype that should be tested.
Objective: We studied the relative distribution of gBRCA1 and gBRCA2 in unselected populations of women with breast cancer and in unaffected individuals. We also analyzed the proportion of estrogen receptor (ER)-positive (ER+) tumors in unselected breast cancer patients with gBRCA.
Design: We performed a meta-analysis of studies of unselected breast cancer that analyzed the relative contribution of gBRCA1 versus gBRCA2 among unselected breast cancer cases in gBRCA carriers. We then performed a meta-analysis of gBRCA 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 breast cancer cases in unselected patients with gBRCA (n = 108,699) and 60% of unaffected individuals (n = 238,973) as compared with 38% of the largest gBRCA family cohort (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 breast cancer patients carried gBRCA1 and gBRCA2, respectively. In a population of 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 gBRCA. 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 gBRCA were ER+ (n = 86,870).
Conclusions: This meta-analysis showed that gBRCA2 carriage is predominant in unselected breast cancer patients and unaffected individuals. ER+ tumors among women with gBRCA-related breast cancer are predominant and have been underestimated. Because PARPi agents improve progression-free survival with ER+ gBRCA breast cancer in most clinical trials, breast cancer should be considered, regardless of ER status, for BRCA1/2 screening for therapeutic purposes.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje