In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 1029-1029
Kurzfassung:
1029 Background: Approximately 5-10% of breast cancer are hereditary. Variant allele frequency (VAF) of hereditary breast cancer predisposition genes in circulating tumor DNA (ctDNA) may be useful for detecting presumed germline pathogenic variants. Methods: One hundred and sixty-eight patients with advanced breast cancer (ABC) who underwent ctDNA and tumor tissue sequencing analyses in the SCRUM-Japan MONSTAR-SCREEN, a cancer genome screening project in Japan, from December 2019 to November 2021 were included. The patients were tested and monitored for their genomic alterations by FoundationOne Liquid assay or FoundationOne Liquid CDx assay. The pathogenic variants (PV) of hereditary breast cancer predisposition genes with VAF of 30% or higher in ctDNA were defined as PGPV. The VAF of BRCA1/2 on ctDNA analyses in BRCA1/2 germline pathogenic variant (GPV) carriers and the prevalence of PGPV in five hereditary breast cancer predisposition genes, including ATM, BRCA1, BRCA2, CHEK2, and PALB2, were investigated. Results: From 168 patients with ABC, including 115 Luminal, 32 HER2-positive, and 21 triple negative breast cancer, with a median age of 58 years, 39 PVs in 5 genes were identified with a median VAF of 0.62% (range: 0.1-84.77). ctDNA identified GPV of known BRCA1/2 GPV carriers (1 with BRCA1 and 6 with BRCA2) , with a median VAF of 51.4% (range: 48.2-77.5). The VAF of GPV on ctDNA were higher than 30% in subsequent consecutive samples. Among 161 patients with ABC, excluding 7 known BRCA1/2 GPV carriers, 6 PGPV (1 with BRCA1, 3 with BRCA2, and 2 with PALB2) were detected, with a median VAF of 65.5% (range: 51.2-84.8). Subsequent confirmatory tests were performed for two PGPV, and the variants were confirmed to be of germline origin. Conclusions: VAF on ctDNA analysis can help to easily detect PGPV of hereditary breast cancer predisposition genes. The PGPV detected in ctDNA analysis should be validated by established germline tests, and the results could provide opportunities for targeted therapies, as well as cancer risk assessment of patients and their relatives.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2022.40.16_suppl.1029
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2022
ZDB Id:
2005181-5
