biostudies-literatureScandino RMinistero della Salute (Ministry of Health, Italy)25https://www.ebi.ac.uk/biostudies/studies/S-EPMC11890748biostudies-literatureUnknown11(1)Cell-free DNA (cfDNA) extracted from peripheral blood has emerged as a crucial biomarker source in oncology research. To enhance the detection of somatic copy number alterations (SCNAs) and circulating tumor DNA (ctDNA), we developed eSENSES, a 2 Mb breast cancer-targeted NGS panel. It includes 15,000 genome-wide SNPs, 500 focal SNPs in breast cancer driver regions, and exons from 81 commonly altered genes, alongside a custom computational approach. We assessed the performance of eSENSES using both synthetic and clinical samples showing that eSENSES can detect ctDNA levels below 1%, exhibiting high sensitivity and specificity at 2-3% ctDNA levels. In patients with metastatic breast cancer, ctDNA estimations correlated with disease progression. When compared with other technologies and statNPJ breast cancerEnabling sensitive and precise detection of ctDNA through somatic copy number aberrations in breast cancer.PMC11890748GR-2018-12365195Biagioni CPestrin MCasiraghi NNardone AGalardi FMoretti ERomagnoli DTonina AMalorni LPaoli MScandino RBiganzoli LGenovese MBenelli MMigliaccio IRomanel AfalseEnabling sensitive and precise detection of ctDNA through somatic copy number aberrations in breast cancer.Cell-free DNA (cfDNA) extracted from peripheral blood has emerged as a crucial biomarker source in oncology research. To enhance the detection of somatic copy number alterations (SCNAs) and circulating tumor DNA (ctDNA), we developed eSENSES, a 2 Mb breast cancer-targeted NGS panel. It includes 15,000 genome-wide SNPs, 500 focal SNPs in breast cancer driver regions, and exons from 81 commonly altered genes, alongside a custom computational approach. We assessed the performance of eSENSES using both synthetic and clinical samples showing that eSENSES can detect ctDNA levels below 1%, exhibiting high sensitivity and specificity at 2-3% ctDNA levels. In patients with metastatic breast cancer, ctDNA estimations correlated with disease progression. When compared with other technologies and stat2025-01-01T00:00:00Z2025 Mar2025-04-04T08:23:08.344Z2025-04-04T08:23:08.344ZS-EPMC118907484005752710.1038/s41523-025-00739-6