Prevalence of BRCA1 and BRCA2 pathogenic variants in a large, unselected breast cancer cohort.
BRCA1
BRCA2
breast cancer
clinical testing
next-generation sequencing
prediction
screening criteria
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 03 2019
01 03 2019
Historique:
received:
03
05
2018
revised:
30
07
2018
accepted:
09
08
2018
pubmed:
4
9
2018
medline:
6
5
2019
entrez:
4
9
2018
Statut:
ppublish
Résumé
Breast cancer patients with BRCA1/2-driven tumors may benefit from targeted therapy. It is not clear whether current BRCA screening guidelines are effective at identifying these patients. The purpose of our study was to evaluate the prevalence of inherited BRCA1/2 pathogenic variants in a large, clinically representative breast cancer cohort and to estimate the proportion of BRCA1/2 carriers not detected by selectively screening individuals with the highest probability of being carriers according to current clinical guidelines. The study included 5,122 unselected Swedish breast cancer patients diagnosed from 2001 to 2008. Target sequence enrichment (48.48 Fluidigm Access Arrays) and sequencing were performed (Illumina Hi-Seq 2,500 instrument, v4 chemistry). Differences in patient and tumor characteristics of BRCA1/2 carriers who were already identified as part of clinical BRCA1/2 testing routines and additional BRCA1/2 carriers found by sequencing the entire study population were compared using logistic regression models. Ninety-two of 5,099 patients with valid variant calls were identified as BRCA1/2 carriers by screening all study participants (1.8%). Only 416 study participants (8.2%) were screened as part of clinical practice, but this identified 35 out of 92 carriers (38.0%). Clinically identified carriers were younger, less likely postmenopausal and more likely to be associated with familiar ovarian cancer compared to the additional carriers identified by screening all patients. More BRCA2 (34/42, 81.0%) than BRCA1 carriers (23/50, 46%) were missed by clinical screening. In conclusion, BRCA1/2 mutation prevalence in unselected breast cancer patients was 1.8%. Six in ten BRCA carriers were not detected by selective clinical screening of individuals.
Identifiants
pubmed: 30175445
doi: 10.1002/ijc.31841
pmc: PMC6320715
mid: NIHMS993078
doi:
Substances chimiques
BRCA1 Protein
0
BRCA1 protein, human
0
BRCA2 Protein
0
BRCA2 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1195-1204Subventions
Organisme : Wellcome Trust
ID : 203477/Z/16/Z
Pays : United Kingdom
Organisme : Intramural NIH HHS
ID : Z99 HG999999
Pays : United States
Organisme : Cancer Research UK
ID : C1287/A16563
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C8197/A16565
Pays : United Kingdom
Informations de copyright
© 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
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