Multigene assessment of genetic risk for women for two or more breast cancers.
BRCA1
BRCA2
Breast cancer
Hereditary breast cancer
Multiple breast cancers
Second breast cancer
Journal
Breast cancer research and treatment
ISSN: 1573-7217
Titre abrégé: Breast Cancer Res Treat
Pays: Netherlands
ID NLM: 8111104
Informations de publication
Date de publication:
Aug 2021
Aug 2021
Historique:
received:
03
11
2020
accepted:
16
03
2021
pubmed:
8
4
2021
medline:
14
7
2021
entrez:
7
4
2021
Statut:
ppublish
Résumé
The prevalence, penetrance, and spectrum of pathogenic variants that predispose women to two or more breast cancers is largely unknown. We queried clinical and genetic data from women with one or more breast cancer diagnosis who received multigene panel testing between 2013 and 2018. Clinical data were obtained from provider-completed test request forms. For each gene on the panel, a multivariable logistic regression model was constructed to test for association with risk of multiple breast cancer diagnoses. Models accounted for age of diagnosis, personal and family cancer history, and ancestry. Results are reported as odds ratios (ORs) with 95% confidence intervals (CIs). This study included 98,979 patients: 88,759 (89.7%) with a single breast cancer and 10,220 (10.3%) with ≥ 2 breast cancers. Of women with two or more breast cancers, 13.2% had a pathogenic variant in a cancer predisposition gene compared to 9.4% with a single breast cancer. BRCA1, BRCA2, CDH1, CHEK2, MSH6, PALB2, PTEN, and TP53 were significantly associated with two or more breast cancers, with ORs ranging from 1.35 for CHEK2 to 3.80 for PTEN. Overall, pathogenic variants in all breast cancer risk genes combined were associated with both metachronous (OR 1.65, 95% CI 1.53-1.79, p = 7.2 × 10 This study demonstrated that several high and moderate penetrance breast cancer susceptibility genes are associated with ≥ 2 breast cancers, affirming the association of two or more breast cancers with diverse genetic etiologies.
Identifiants
pubmed: 33826040
doi: 10.1007/s10549-021-06201-y
pii: 10.1007/s10549-021-06201-y
pmc: PMC8803157
mid: NIHMS1770786
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
759-768Subventions
Organisme : NCI NIH HHS
ID : R01 CA242218
Pays : United States
Organisme : NIH HHS
ID : P30CA033572
Pays : United States
Organisme : NCI NIH HHS
ID : K08CA234394
Pays : United States
Organisme : NCI NIH HHS
ID : R01CA242218
Pays : United States
Organisme : Conquer Cancer Foundation
ID : Research Professorship in Breast Cancer Diaparities
Organisme : NCI NIH HHS
ID : K08 CA234394
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA033572
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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