Identification and Management of Pathogenic Variants in BRCA1, BRCA2, and PALB2 in a Tumor-Only Genomic Testing Program.
Clin Cancer Res
; 28(11): 2349-2360, 2022 06 01.
Article
em En
| MEDLINE
| ID: mdl-35363308
ABSTRACT
PURPOSE:
Tumor-only genomic testing can uncover somatic and germline pathogenic variants [pathogenic/likely pathogenic (P/LP)] in cancer predisposition genes. We describe the prevalence of P/LPs in BRCA1/2 and PALB2 (B1B2P2) across malignancies and the frequency of clinical germline testing (CGT) in patients with P/LPs in B1B2P2 identified on tumor-only testing. EXPERIMENTALDESIGN:
Among 7,575 patients with cancer tested between 2016 and 2018 with the OncoPanel tumor-only sequencing assay, we characterized P/LP frequencies by tumor type, receipt of CGT prior to or within 12 months after OncoPanel, and factors associated with CGT.RESULTS:
272 (3.6%) patients had OncoPanel-detected P/LPs in B1B2P2 37.5% of P/LPs were in BRCA-related cancers; the remainder were in non-BRCA tumors. P/LPs were detected in ≥5% of breast, pancreatic, prostate, ovarian, nonmelanoma skin, endometrial, small cell lung, and colorectal cancers. 37.9% of patients with P/LPs received CGT prior to OncoPanel; an additional 10.7% underwent CGT within 12 months of OncoPanel. Among 132 with CGT, 88.6% had ≥1 clinical factor for CGT compared with 47.1% who did not undergo CGT. Patients with BRCA tumors were more likely to have CGT compared with those without (81.4% vs. 29.0%, P < 0.0001). Among patients with CGT, 70.5% (93/132) of P/LPs were germline.CONCLUSIONS:
Tumor-only genomic testing identified P/LPs in B1B2P2 in 3.6% of patients. 52.9% of patients with tumor-detected P/LPs and without CGT did not meet personal or family history criteria for CGT. In addition, some patients with tumor-detected P/LPs were not referred for CGT, especially those with non-BRCA tumors. Given implications for treatment selection and familial cancer risk, processes to reliably trigger CGT from tumor-genomic findings are needed.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteína BRCA1
/
Proteína BRCA2
/
Proteína do Grupo de Complementação N da Anemia de Fanconi
/
Neoplasias
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Clin Cancer Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2022
Tipo de documento:
Article