Evidence map›Paper›PMID 34480095›Full record

ArticleBritish journal of cancer2021

Patterns of genomic change in residual disease after neoadjuvant chemotherapy for estrogen receptor-positive and HER2-negative breast cancer.

Aikaterini Chatzipli, Hervé Bonnefoi, Gaetan MacGrogan, Julie Sentis, David Cameron, Coralie Poncet, EORTC 10994/BIG 1-00 Consortium, Richard Iggo

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00017095 (First Prospective Intergroup Translational Research Trial Assessing the Potential Predictive Value of p53 Using a Functional Assay in Yeast in Patients With Locally Advanced/Inflammatory or Large Operable Breast Cancer Prospectively Randomised to a Taxane Versus a Non Taxane Regimen), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 37% 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.

NCT00017095 phase3completednot on this map

First Prospective Intergroup Translational Research Trial Assessing the Potential Predictive Value of p53 Using a Functional Assay in Yeast in Patients With Locally Advanced/Inflammatory or Large Operable Breast Cancer Prospectively Randomised to a Taxane Versus a Non Taxane Regimen

TypeinterventionalSponsorEuropean Organisation for Research and Treatment of Cancer - EORTCRan2001Enrolled1,856ConditionsBreast CancerArmsfilgrastim, cyclophosphamide, docetaxel, epirubicin hydrochloride, fluorouracil
3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
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

8 authors at 13 institutions in 6 countries.

Aikaterini Chatzipli *Wellcome Sanger Institute, Cambridge, UK.
Hervé Bonnefoi *Institut Bergonié, INSERM U1218, University of Bordeaux, Bordeaux, France.ORCID http://orcid.org/0000-0003-4293-9748
Gaetan MacGroganInstitut Bergonié, INSERM U1218, University of Bordeaux, Bordeaux, France.
Julie SentisInstitut Bergonié, INSERM U1218, University of Bordeaux, Bordeaux, France.
David CameronUniversity of Edinburgh, Edinburgh, UK.
Coralie PoncetEORTC Data Centre, Brussels, Belgium.
EORTC 10994/BIG 1-00 Consortium
Richard IggoInstitut Bergonié, INSERM U1218, University of Bordeaux, Bordeaux, France. Richard.Iggo@u-bordeaux.fr.ORCID http://orcid.org/0000-0002-8822-9111
Université de Bordeaux · FRInstitut de Cancérologie de l'Ouest · FRCentre Henri BecquerelEuropean Organisation for Research and Treatment of Cancer · BEGdańsk Medical University · PLHôpital Beau-Séjour · CHHôpital René Huguenin · FRInstitute of Oncology Ljubljana · SIRoche (France) · FRUniversité Libre de Bruxelles · BEUniversity Hospital of Lausanne · CHUniversity of Edinburgh · GBWellcome Sanger Institute · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTreatment of patients with residual disease after neoadjuvant chemotherapy for breast cancer is an unmet clinical need. We hypothesised that tumour subclones showing expansion in residual disease after chemotherapy would contain mutations conferring drug resistance.

methodsWe studied oestrogen receptor and/or progesterone receptor-positive, HER2-negative tumours from 42 patients in the EORTC 10994/BIG 00-01 trial who failed to achieve a pathological complete response. Genes commonly mutated in breast cancer were sequenced in pre and post-treatment samples.

resultsOncogenic driver mutations were commonest in PIK3CA (38% of tumours), GATA3 (29%), CDH1 (17%), TP53 (17%) and CBFB (12%); and amplification was commonest for CCND1 (26% of tumours) and FGFR1 (26%). The variant allele fraction frequently changed after treatment, indicating that subclones had expanded and contracted, but there were changes in both directions for all of the commonly mutated genes.

conclusionsWe found no evidence that expansion of clones containing recurrent oncogenic driver mutations is responsible for resistance to neoadjuvant chemotherapy. The persistence of classic oncogenic mutations in pathways for which targeted therapies are now available highlights their importance as drug targets in patients who have failed chemotherapy but provides no support for a direct role of driver oncogenes in resistance to chemotherapy. CLINICALTRIALS.GOV: EORTC 10994/BIG 1-00 Trial registration number NCT00017095.

Indexed as

Gene AmplificationMutationAntineoplastic AgentsBreast NeoplasmsErb-b2 Receptor Tyrosine KinasesFemaleGene FrequencyGene Regulatory NetworksHumansNeoadjuvant TherapyNeoplasm, ResidualReceptors, EstrogenSequence Analysis, DNATreatment OutcomeAntineoplastic AgentsERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesReceptors, Estrogen

Identifiers

PMID34480095
PMCPMC8575785
OpenAlexW3197274728

What OpenQuestion holds

Textmetadata
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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.