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A breast cancer blood test that tracked hundreds of each patient's tumour mutations found leftover disease that predicted relapse, but most patients' tumours had far fewer mutations to track, and that set how sensitive the test could be.
The authors tracked hundreds of patient-specific mutations in cell-free DNA with an error rate 1,000-fold lower than conventional sequencing, after whole-exome sequencing of each tumour. In a dilution series the approach was 100-fold more sensitive than digital droplet PCR when tracking 488 mutations, but most patients had fewer identifiable tumour mutations to track (median 57, range 2 to 346). Clinical sensitivity was 81 per cent (13 of 16) in newly diagnosed metastatic breast cancer, 23 per cent (7 of 30) after surgery and 19 per cent (6 of 32) at one year in early-stage disease, highest in patients with the most mutations to track. Residual disease at one year was associated with distant recurrence (hazard ratio 20.8, 95% CI 7.3 to 58.9), with a median lead time of 18.9 months.
In breast cancer, how sensitive a personalised blood test can be is limited by how many mutations the tumour has to track, and breast tumours have relatively few. That same shortage is what stops a test saying which part of the tumour is left.
Shares Tumour-informed versus tumour-naive ctDNA assays, Minimal / molecular residual disease (MRD), Circulating tumour DNA (ctDNA), MRD / molecular residual disease testing.
Shares Naming which clone or phenotype is left after treatment, ctDNA MRD positivity (molecular residual disease after curative treatment), Tumour-informed versus tumour-naive ctDNA assays, Minimal / molecular residual disease (MRD).
Shares Naming which clone or phenotype is left after treatment, Tumour-informed versus tumour-naive ctDNA assays, Minimal / molecular residual disease (MRD), Circulating tumour DNA (ctDNA).
Shares Naming which clone or phenotype is left after treatment, ctDNA MRD positivity (molecular residual disease after curative treatment), Tumour-informed versus tumour-naive ctDNA assays, Minimal / molecular residual disease (MRD).
Shares Tumour-informed versus tumour-naive ctDNA assays, Minimal / molecular residual disease (MRD), Circulating tumour DNA (ctDNA), MRD / molecular residual disease testing.
Shares ctDNA MRD positivity (molecular residual disease after curative treatment), Clinical Cancer Research, Minimal / molecular residual disease (MRD), Circulating tumour DNA (ctDNA).
Shares ctDNA MRD positivity (molecular residual disease after curative treatment), Clinical Cancer Research, Minimal / molecular residual disease (MRD), Circulating tumour DNA (ctDNA).
Shares ctDNA MRD positivity (molecular residual disease after curative treatment), Tumour-informed versus tumour-naive ctDNA assays, Minimal / molecular residual disease (MRD), Circulating tumour DNA (ctDNA).
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