Evidence map›Paper›PMID 35948919›Full record

ArticleGenome medicine2022

Clonal evolution in primary breast cancers under sequential epirubicin and docetaxel monotherapy.

Andreas Venizelos, Christina Engebrethsen, Wei Deng, Jürgen Geisler, Stephanie Geisler, Gjertrud T Iversen, Turid Aas, Hildegunn S Aase, Manouchehr Seyedzadeh, Eli Sihn Steinskog and 8 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00496795 (Molecular Markers Predictive Response to Dose Dense Chemotherapy With Epirubicin and Docetaxel in Sequences for Locally Advanced Breast Cancer.), which is not on this map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.4field-weighted citation impact, top 18% 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.

NCT00496795 phase2unknown statusnot on this map

Molecular Markers Predictive Response to Dose Dense Chemotherapy With Epirubicin and Docetaxel in Sequences for Locally Advanced Breast Cancer.

TypeinterventionalSponsorUniversity of BergenRan2007 to 2026Enrolled100ConditionsStage III Breast Cancer AJCC V7Armsepirubicin/docetaxel sequential
3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 15 citations in OpenAlex.

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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

18 authors at 3 institutions in 1 country.

Andreas VenizelosK.G.Jebsen Center for Genome Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway.ORCID 0000-0003-4121-338X
Christina EngebrethsenK.G.Jebsen Center for Genome Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway.
Wei DengK.G.Jebsen Center for Genome Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway.
Jürgen GeislerDepartment of Oncology, Haukeland University Hospital, Bergen, Norway.
Stephanie GeislerDepartment of Oncology, Haukeland University Hospital, Bergen, Norway.
Gjertrud T IversenK.G.Jebsen Center for Genome Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway.
Turid AasDepartment of Surgery, Haukeland University Hospital, Bergen, Norway.
Hildegunn S AaseDepartment of Radiology, Haukeland University Hospital, Bergen, Norway.
Manouchehr SeyedzadehDepartment of Radiology, Haukeland University Hospital, Bergen, Norway.
Eli Sihn SteinskogDepartment of Oncology, Haukeland University Hospital, Bergen, Norway.
Ola MyklebostDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Sigve NakkenDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Daniel VodakDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Eivind HovigDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Leonardo A Meza-ZepedaDepartment of Tumor Biology, Institute of Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Per E LønningK.G.Jebsen Center for Genome Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway.
Stian Knappskog *K.G.Jebsen Center for Genome Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway. stian.knappskog@uib.no.ORCID 0000-0002-4153-1655
Hans P Eikesdal *K.G.Jebsen Center for Genome Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway. hans.eikesdal@uib.no.ORCID 0000-0003-4086-0147
Haukeland University Hospital · NOOslo University Hospital · NOAkershus University Hospital · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSubclonal evolution during primary breast cancer treatment is largely unexplored. We aimed to assess the dynamic changes in subclonal composition of treatment-naïve breast cancers during neoadjuvant chemotherapy.

methodsWe performed whole exome sequencing of tumor biopsies collected before, at therapy switch, and after treatment with sequential epirubicin and docetaxel monotherapy in 51 out of 109 patients with primary breast cancer, who were included in a prospectively registered, neoadjuvant single-arm phase II trial.

resultsThere was a profound and differential redistribution of subclones during epirubicin and docetaxel treatment, regardless of therapy response. While truncal mutations and main subclones persisted, smaller subclones frequently appeared or disappeared. Reassessment of raw data, beyond formal mutation calling, indicated that the majority of subclones seemingly appearing during treatment were in fact present in pretreatment breast cancers, below conventional detection limits. Likewise, subclones which seemingly disappeared were still present, below detection limits, in most cases where tumor tissue remained. Tumor mutational burden (TMB) dropped during neoadjuvant therapy, and copy number analysis demonstrated specific genomic regions to be systematically lost or gained for each of the two chemotherapeutics.

conclusionsSequential epirubicin and docetaxel monotherapy caused profound redistribution of smaller subclones in primary breast cancer, while early truncal mutations and major subclones generally persisted through treatment.

trial registrationClinicalTrials.gov, NCT00496795 , registered on July 4, 2007.

Indexed as

Breast NeoplasmsAntineoplastic Combined Chemotherapy ProtocolsClonal EvolutionCyclophosphamideDocetaxelEpirubicinFemaleHumansNeoadjuvant TherapyTaxoidsCyclophosphamideDocetaxelEpirubicinTaxoidsBreast cancerChemoresistanceClonal evolutionNeoadjuvant chemotherapy

Identifiers

PMID35948919
PMCPMC9367103
OpenAlexW4290985749

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Registered trials

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.