# Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy With Disease Recurrence in Patients With Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial

Source: https://onco.cc/key-papers/paper-radovich-ctdna-ctc-bre12-158-jama-oncol-2020/  
OnCo record `paper-radovich-ctdna-ctc-bre12-158-jama-oncol-2020` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

In 196 women with triple-negative breast cancer left with residual tumour after pre-surgery chemotherapy, finding tumour DNA in the blood after surgery tripled the risk of distant relapse and quadrupled the risk of death; at two years 56 percent versus 81 percent were free of distant disease.

## Summary

Radovich, Jiang, Hancock, Chitambar and colleagues report a preplanned secondary analysis of BRE12-158, a phase 2 trial that randomised patients with early-stage triple-negative breast cancer and residual disease after neoadjuvant chemotherapy to genomically directed therapy or physician's choice; 196 patients had blood drawn at treatment assignment, with ctDNA (FoundationACT or FoundationOne Liquid) analysed for survival in 142 and circulating tumour cells in 123, median follow-up 17.2 months. ctDNA detection was associated with inferior distant disease-free survival (median 32.5 months versus not reached; hazard ratio 2.99, 95 percent confidence interval 1.38 to 6.48, p=0.006; two-year probability 56 versus 81 percent), disease-free survival (2.67) and overall survival (4.16, 1.66 to 10.42, p=0.002). Patients positive for both ctDNA and circulating tumour cells had a distant disease-free survival hazard ratio of 5.29 versus double-negative patients (two-year probability 52 versus 89 percent) and overall survival hazard ratio 8.60.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: tnbc-evidence
- Journal: JAMA Oncology
- Year: 2020
- DOI: 10.1001/jamaoncol.2020.2295
- Authors: Radovich M, Jiang G, Hancock BA, et al.
- Findings: ctDNA detection after neoadjuvant chemotherapy: distant disease-free survival hazard ratio 2.99 (95 percent CI 1.38 to 6.48), p=0.006; two-year probability 56 vs 81 percent.; Overall survival hazard ratio 4.16 (1.66 to 10.42), p=0.002.; ctDNA and circulating tumour cell double positivity: distant disease-free survival hazard ratio 5.29; two-year probability 52 vs 89 percent.
- What it means: The proof that a blood test can split residual-disease patients into those likely to relapse and those likely cured, the premise of the ctDNA-guided adjuvant idea; no completed trial has yet acted on the result.
- Caveats: Short follow-up (17.2 months) and a tumour-agnostic assay less sensitive than tumour-informed tests.; Secondary analysis of a trial whose primary comparison was negative.

## Sources

- JAMA Oncol 2020: https://doi.org/10.1001/jamaoncol.2020.2295
- PubMed: https://pubmed.ncbi.nlm.nih.gov/32644110/
- ClinicalTrials.gov NCT02101385: https://clinicaltrials.gov/study/NCT02101385

## Connected records

- roadmaps: [ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment](https://onco.cc/roadmaps/ctdna-tests/), [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- key papers: [Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer](https://onco.cc/key-papers/paper-turner-c-trak-tn-ctdna-pembrolizumab-ann-oncol-2023/)
- biomarkers: [ctDNA MRD positivity (molecular residual disease after curative treatment)](https://onco.cc/biomarkers/ctdna-mrd-positive/)
- cancers: [Early triple-negative breast cancer](https://onco.cc/cancers/tnbc-early/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- drugs: [FoundationOne CDx / Liquid CDx](https://onco.cc/drugs/foundationone-cdx/)
- companies: [Foundation Medicine (Roche)](https://onco.cc/companies/foundation-medicine/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Hazard ratio (HR)](https://onco.cc/terms/hazard-ratio/), [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Residual cancer burden (RCB)](https://onco.cc/terms/rcb/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/)
- journals: [JAMA Oncology](https://onco.cc/journals/jama-oncology/)
- ideas: [ctDNA-guided adjuvant decisions after residual disease: escalate the positive, spare the negative](https://onco.cc/ideas/idea-tnbc-ctdna-guided-adjuvant-decisions/)

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