# Assessment of molecular relapse detection in early-stage breast cancer

Source: https://onco.cc/key-papers/paper-garcia-murillas-molecular-relapse-detection-jama-oncol-2019/  
OnCo record `paper-garcia-murillas-molecular-relapse-detection-jama-oncol-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In 101 women followed with blood tests every few months after treatment for early breast cancer, ctDNA appeared a median of 10.7 months before relapse showed on scans and caught 22 of 23 distant relapses outside the brain but only one of six brain-only relapses.

## Summary

Prospective multicentre validation study at five UK centres (2011 to 2016) of women with early breast cancer of any subtype receiving neoadjuvant or adjuvant chemotherapy; 170 recruited, 101 with mutations identified formed the main cohort, and 144 the combined cohort. Personalised digital PCR assays tracked primary tumour mutations in plasma every three months for a year and six-monthly thereafter. ctDNA detection during follow-up was associated with relapse (HR 25.2; P less than .001), as was detection at diagnosis (HR 5.8). Median lead time was 10.7 months; distant extracranial relapse was detected by ctDNA in 22 of 23 (96%) but brain-only metastasis in 1 of 6 (17%).

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: JAMA Oncology
- Year: 2019
- DOI: 10.1001/jamaoncol.2019.1838
- Authors: Garcia-Murillas I, Chopra N, Comino-Mendez I, et al.
- Findings: ctDNA during follow-up: relapse HR 25.2; at diagnosis HR 5.8.; Median lead time 10.7 months; extracranial relapse detected in 96%, brain-only in 17%.
- What it means: For TNBC, where brain metastases are common, the blind spot matters: a negative ctDNA test does not exclude intracranial relapse.
- Caveats: All subtypes; TNBC-specific numbers are not in the abstract.; Digital PCR assays of a few variants.

## Sources

- Garcia-Murillas et al., JAMA Oncol 2019: molecular relapse detection in 101 early breast cancer patients: https://doi.org/10.1001/jamaoncol.2019.1838
- PubMed: https://pubmed.ncbi.nlm.nih.gov/31369045/

## Connected records

- biomarkers: [ctDNA MRD positivity (molecular residual disease after curative treatment)](https://onco.cc/biomarkers/ctdna-mrd-positive/)
- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- institutions: [The Institute of Cancer Research](https://onco.cc/institutions/icr-london/), [The Royal Marsden](https://onco.cc/institutions/royal-marsden/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/)
- people: [Nicholas Turner](https://onco.cc/people/nicholas-turner/)
- journals: [JAMA Oncology](https://onco.cc/journals/jama-oncology/)

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