# Comparison of tumor-informed and tumor-naïve sequencing assays for ctDNA detection in breast cancer

Source: https://onco.cc/key-papers/paper-santonja-tumour-informed-vs-naive-breast-embo-mol-med-2023/  
OnCo record `paper-santonja-tumour-informed-vs-naive-breast-embo-mol-med-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In breast cancer, blood tests built from each patient's tumour mutations found the smallest amounts of tumour DNA, down to a few parts per million when thousands of mutations were tracked.

## Summary

Serial plasma from patients with breast cancer was analysed with tumour-informed and tumour-naive assays for structural variants, single-nucleotide variants and copy-number changes, by multiplex PCR, hybrid capture and whole-genome sequencing at different depths. ctDNA dynamics and allele fractions were highly concordant between assays, and tumour-informed assays were the most sensitive at low concentrations. Hybrid capture targeting 1,347 to 7,491 tumour-identified mutations detected ctDNA down to an allele fraction of 0.00024 per cent (2.4 parts per million); multiplex PCR targeting 21 to 47 structural variants detected it down to 0.00047 per cent (4.7 parts per million).

## Fields

- Kind: Key paper
- Last checked: 2026-11-04
- Journal: EMBO Molecular Medicine
- Year: 2023
- DOI: 10.15252/emmm.202216505
- Authors: Santonja A, Cooper WN, Eldridge MD, et al.
- Findings: Hybrid capture of 1,347 to 7,491 mutations: detection down to 2.4 ppm.; Multiplex PCR of 21 to 47 structural variants: detection down to 4.7 ppm.
- What it means: Parts-per-million detection in breast cancer needs thousands of tracked mutations or a smaller set of structural variants; detection still pools them all, so it does not say which clone is present.
- Caveats: Lowest detected values, not 95 per cent limits of detection.

## Sources

- Santonja et al., EMBO Mol Med 2023: https://doi.org/10.15252/emmm.202216505
- PubMed: https://pubmed.ncbi.nlm.nih.gov/37161793/

## Connected records

- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/)
- technologies: [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Tumour-informed versus tumour-naive ctDNA assays](https://onco.cc/terms/tumour-informed-assay/)

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