Evidence map›Paper›PMID 27760227›Full record

ArticlePloS one2016

Reproducibility of Digital PCR Assays for Circulating Tumor DNA Analysis in Advanced Breast Cancer.

Sarah Hrebien, Ben O'Leary, Matthew Beaney, Gaia Schiavon, Charlotte Fribbens, Amarjit Bhambra, Richard Johnson, Isaac Garcia-Murillas, Nicholas Turner

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 3 pooled it
2.5field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 3 syntheses or guidelines pooled it, 36 citations in OpenAlex.

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  19. Analysis ofOncotarget · 2017
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Sarah HrebienThe Breast Cancer Now Research Centre, The Institute of Cancer Research, London, SW3 6JB, United Kingdom.
Ben O'LearyThe Breast Cancer Now Research Centre, The Institute of Cancer Research, London, SW3 6JB, United Kingdom.
Matthew BeaneyThe Breast Cancer Now Research Centre, The Institute of Cancer Research, London, SW3 6JB, United Kingdom.
Gaia SchiavonTranslational Science, Oncology iMed, AstraZeneca, Cambridge, CB4 0WG, United Kingdom.
Charlotte FribbensThe Breast Cancer Now Research Centre, The Institute of Cancer Research, London, SW3 6JB, United Kingdom.
Amarjit BhambraBreast Unit, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom.
Richard JohnsonBreast Unit, Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom.
Isaac Garcia-MurillasThe Breast Cancer Now Research Centre, The Institute of Cancer Research, London, SW3 6JB, United Kingdom.ORCID http://orcid.org/0000-0001-8183-7969
Nicholas TurnerThe Breast Cancer Now Research Centre, The Institute of Cancer Research, London, SW3 6JB, United Kingdom.
Royal Marsden NHS Foundation Trust · GBInstitute of Cancer Research · GBAstraZeneca (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Circulating tumor DNA (ctDNA) analysis has the potential to allow non-invasive analysis of tumor mutations in advanced cancer. In this study we assessed the reproducibility of digital PCR (dPCR) assays of circulating tumor DNA in a cohort of patients with advanced breast cancer and assessed delayed plasma processing using cell free DNA preservative tubes. We recruited a cohort of 96 paired samples from 71 women with advanced breast cancer who had paired blood samples processed either immediately or delayed in preservative tubes with processing 48-72 hours after collection. Plasma DNA was analysed with multiplex digital PCR (mdPCR) assays for hotspot mutations in PIK3CA, ESR1 and ERBB2, and for AKT1 E17K. There was 94.8% (91/96) agreement in mutation calling between immediate and delayed processed tubes, kappa 0.88 95% CI 0.77-0.98). Discordance in mutation calling resulted from low allele frequency and likely stochastic effects. In concordant samples there was high correlation in mutant copies per ml plasma (r2 = 0.98; p<0.0001). There was elevation of total cell free plasma DNA concentrations in 10.3% of delayed processed tubes, although overall quantification of total cell free plasma DNA had similar prognostic effects in immediate (HR 3.6) and delayed (HR 3.0) tubes. There was moderate agreement in changes in allele fraction between sequential samples in quantitative mutation tracking (r = 0.84, p = 0.0002). Delayed processing of samples using preservative tubes allows for centralized ctDNA digital PCR mutation screening in advanced breast cancer. The potential of preservative tubes in quantitative mutation tracking requires further research.

Indexed as

MutationBiomarkers, TumorBreast NeoplasmsCell Line, TumorDNA, NeoplasmElectronic Data ProcessingFemaleHumansMCF-7 CellsMiddle AgedMultiplex Polymerase Chain ReactionPrognosisReproducibility of ResultsBiomarkers, TumorDNA, Neoplasm

Identifiers

PMID27760227
PMCPMC5070760
OpenAlexW2534818791

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.