Enabling 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 state-of-the-art approaches, eSENSES demonstrated enhanced performance. eSENSES provides a reliable, powerful and cost-effective tool for monitoring disease progression and guiding therapeutic decisions in breast cancer patients.
Authors
- Marta Pestrin
- Matteo Benelli (ORCID: https://orcid.org/0000-0003-1227-356X)
- Maria Inés Genovese (ORCID: https://orcid.org/0000-0002-1322-3129)
- Marta Paoli (ORCID: https://orcid.org/0000-0001-5047-5571)
- Alessandro Romanel (ORCID: https://orcid.org/0000-0003-4855-8620)
- Dario Romagnoli (ORCID: https://orcid.org/0000-0002-2465-2463)
- Laura Biganzoli (ORCID: https://orcid.org/0000-0001-7989-8658)
- Agostina Nardone (ORCID: https://orcid.org/0000-0003-3277-1101)
- Francesca Galardi
- Chiara Biagioni (ORCID: https://orcid.org/0000-0002-7908-4854)
- Nicola Casiraghi (ORCID: https://orcid.org/0000-0002-5390-544X)
- Riccardo Scandino (ORCID: https://orcid.org/0000-0002-1640-5307)
- Erica Moretti (ORCID: https://orcid.org/0000-0002-8114-4668)
- Luca Malorni (ORCID: https://orcid.org/0000-0002-4297-2997)
- Ilenia Migliaccio (ORCID: https://orcid.org/0000-0001-9055-4522)
- Andrea Tonina
Institutions
- University of Trento (IT)
- Hospital of Prato (IT)
- University of Florence (IT)
Publication Details
- Journal
- npj Breast Cancer
- Published
- 2025-03-08
- DOI
- https://doi.org/10.1038/s41523-025-00739-6
- Citations
- 5
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 4.68
Funders
- Ministero della Salute