Evidence map›Paper›PMID 29298688›Full record

ArticleBMC cancer2018

Enhanced response rate to pegylated liposomal doxorubicin in high grade serous ovarian carcinomas harbouring BRCA1 and BRCA2 aberrations.

Robert L Hollis, Alison M Meynert, Michael Churchman, Tzyvia Rye, Melanie Mackean, Fiona Nussey, Mark J Arends, Andrew H Sims, Colin A Semple, C Simon Herrington and 1 more

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
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

6 citing papers in PubMed, 17 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Predicting Response to Anthracyclines in Ovarian Cancer.International journal of environmental research and public health · 2022
    Review
  5. Article
  6. 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

11 authors at 3 institutions in 1 country.

Robert L HollisNicola Murray Centre for Ovarian Cancer Research, Edinburgh Cancer Research UK Centre, MRC IGMM, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
Alison M MeynertMRC Human Genetics Unit, MRC IGMM, University of Edinburgh, Edinburgh, UK.
Michael ChurchmanNicola Murray Centre for Ovarian Cancer Research, Edinburgh Cancer Research UK Centre, MRC IGMM, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
Tzyvia RyeNicola Murray Centre for Ovarian Cancer Research, Edinburgh Cancer Research UK Centre, MRC IGMM, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
Melanie MackeanEdinburgh Cancer Centre, Western General Hospital, Edinburgh, UK.
Fiona NusseyEdinburgh Cancer Centre, Western General Hospital, Edinburgh, UK.
Mark J ArendsDivision of Pathology, Centre for Comparative Pathology, Edinburgh Cancer Research Centre, MRC IGMM, University of Edinburgh, Edinburgh, UK.
Andrew H SimsNicola Murray Centre for Ovarian Cancer Research, Edinburgh Cancer Research UK Centre, MRC IGMM, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
Colin A SempleMRC Human Genetics Unit, MRC IGMM, University of Edinburgh, Edinburgh, UK.
C Simon HerringtonNicola Murray Centre for Ovarian Cancer Research, Edinburgh Cancer Research UK Centre, MRC IGMM, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
Charlie GourleyNicola Murray Centre for Ovarian Cancer Research, Edinburgh Cancer Research UK Centre, MRC IGMM, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK. charlie.gourley@ed.ac.uk.ORCID 0000-0002-2377-7221
Western General Hospital · GBInstitute of Genetics and Cancer · GBEdinburgh Cancer Research · GB

Funding

Medical Research Council MC_UU_00007/16Medical Research Council MC_UU_12008/2Wellcome Trust
6 · The paper itself

Abstract

backgroundApproximately 10-15% of ovarian carcinomas (OC) are attributed to inherited susceptibility, the majority of which are due to mutations in BRCA1 or BRCA2 (BRCA1/2). These patients display superior clinical outcome, including enhanced sensitivity to platinum-based chemotherapy. Here, we seek to investigate whether BRCA1/2 status influences the response rate to single-agent pegylated liposomal doxorubicin (PLD) in high grade serous (HGS) OC.

methodsOne hundred and forty-eight patients treated with single-agent PLD were identified retrospectively from the Edinburgh Ovarian Cancer Database. DNA was extracted from formalin-fixed paraffin-embedded (FFPE) archival tumour material and sequenced using the Ion Ampliseq BRCA1 and BRCA2 panel. A minimum variant allele frequency threshold was applied to correct for sequencing artefacts associated with formalin fixation.

resultsA superior response rate to PLD was observed in patients with HGS OC who harboured variants likely to affect BRCA1 or BRCA2 function compared to the BRCA1/2 wild-type population (36%, 9 of 25 patients versus 12.1%, 7 of 58 patients; p = 0.016). An enhanced response rate was also seen in patients harbouring only the BRCA1 SNP rs1799950, predicted to be detrimental to BRCA1 function (50%, 3 of 6 patients versus 12.1%, 7 of 58 patients; p = 0.044).

conclusionsThese data demonstrate that HGS OC patients with BRCA1/2 variants predicted damaging to protein function experience superior sensitivity to PLD, consistent with impaired DNA repair. Further characterisation of rs1799950 is now warranted in relation to chemosensitivity and susceptibility to developing ovarian carcinoma.

Indexed as

MutationAdultAgedAged, 80 and overAntibiotics, AntineoplasticBiomarkers, TumorBRCA1 ProteinBRCA2 ProteinCystadenocarcinoma, SerousDoxorubicinFemaleFollow-Up StudiesGenetic Predisposition to DiseaseHumansMiddle AgedNeoplasm GradingAntibiotics, AntineoplasticBiomarkers, TumorBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, humanDoxorubicinliposomal doxorubicinPolyethylene GlycolsBRCA1BRCA2Ovarian cancerPLDH

Identifiers

PMID29298688
PMCPMC5753521
OpenAlexW2781981483

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.