Evidence map›Paper›PMID 26882907›Full record

Trial reportBreast cancer research : BCR2016

Computational pathology of pre-treatment biopsies identifies lymphocyte density as a predictor of response to neoadjuvant chemotherapy in breast cancer.

H Raza Ali, Aliakbar Dariush, Elena Provenzano, Helen Bardwell, Jean E Abraham, Mahesh Iddawela, Anne-Laure Vallier, Louise Hiller, Janet A Dunn, Sarah J Bowden and 9 more

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Breast cancer research : BCR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00070278 (A Phase III Randomized Neoadjuvant Study of Sequential Epirubicin/Cyclophosphamide and Paclitaxel + - Gemcitabine in Poor Risk Early Breast Cancer), which is not on this map. Cited by 50 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 2 pooled it
11.6field-weighted citation impact, top 2% 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.

NCT00070278 phase3unknown statusnot on this map

A Phase III Randomized Neoadjuvant Study of Sequential Epirubicin/Cyclophosphamide and Paclitaxel + - Gemcitabine in Poor Risk Early Breast Cancer

TypeinterventionalSponsorCambridge University Hospitals NHS Foundation TrustRan2005Enrolled800ConditionsBreast CancerArmscyclophosphamide, epirubicin hydrochloride, gemcitabine hydrochloride, paclitaxel, comparative genomic hybridization
3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 89 citations in OpenAlex.

  1. Pooled it
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  16. Spatial Biology of Breast Cancer.Cold Spring Harbor perspectives in medicine · 2024
    Review
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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

19 authors at 8 institutions in 3 countries.

H Raza AliCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK. raza.ali@cruk.cam.ac.uk.
Aliakbar DariushInstitute of Astronomy, University of Cambridge, Cambridge, UK. adariush@ast.cam.ac.uk.
Elena ProvenzanoDepartment of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. elena.provenzano@addenbrookes.nhs.uk.
Helen BardwellCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK. helen.bardwell@cruk.cam.ac.uk.
Jean E AbrahamDepartment of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. ja344@medschl.cam.ac.uk.
Mahesh IddawelaDepartment of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. mahesh.iddawela@monash.edu.
Anne-Laure VallierDepartment of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. Anne-Laure.Vallier@addenbrookes.nhs.uk.
Louise HillerWarwick Clinical Trials Unit, University of Warwick, Coventry, UK. l.hiller@warwick.ac.uk.
Janet A DunnWarwick Clinical Trials Unit, University of Warwick, Coventry, UK. J.A.Dunn@warwick.ac.uk.
Sarah J BowdenCancer Research UK Clinical Trials Unit, Institute for Cancer Studies, The University of Birmingham, Edgbaston, Birmingham, UK. s.j.bowden@bham.ac.uk.
Tamas HickishRoyal Bournemouth Hospital and Bournemouth University, Castle Lane East, Bournemouth, UK. tamas.hickish@rbch.nhs.uk.
Karen McAdamPeterborough and Stamford Hospitals NHS Foundation Trust and Cambridge University Hospital NHS Foundation Trust, Peterborough, UK. karen.mcadam@pbh-tr.nhs.uk.
Stephen HoustonRoyal Surrey County Hospital NHS Foundation Trust, Egerton Road, Guildford, UK. shouston@nhs.net.
Mike J IrwinInstitute of Astronomy, University of Cambridge, Cambridge, UK. mike@ast.cam.ac.uk.
Paul D P PharoahDepartment of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. pp10001@medschl.cam.ac.uk.
James D BrentonCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK. james.brenton@cruk.cam.ac.uk.
Nicholas A WaltonInstitute of Astronomy, University of Cambridge, Cambridge, UK. naw@ast.cam.ac.uk.
Helena M EarlDepartment of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. hme22@cam.ac.uk.
Carlos CaldasCancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK. carlos.caldas@cruk.cam.ac.uk.
University of Cambridge · GBCancer Research UK · GBUniversity of Warwick · GBCancer Research UK Cambridge Center · GBCancer Research UK Clinical Trials Unit · GBPeterborough and Stamford Hospitals NHS Foundation Trust · GBRoyal Bournemouth Hospital · GBRoyal Surrey County Hospital · GB

Funding

Cancer Research UK 10119Cancer Research UK 10124Cancer Research UK 11010Cancer Research UK 15601Cancer Research UK 16465Cancer Research UK 16561Cancer Research UK 16942Cancer Research UK 22905Medical Research Council G0300648Medical Research Council MR/M008975/1
6 · The paper itself

Abstract

backgroundThere is a need to improve prediction of response to chemotherapy in breast cancer in order to improve clinical management and this may be achieved by harnessing computational metrics of tissue pathology. We investigated the association between quantitative image metrics derived from computational analysis of digital pathology slides and response to chemotherapy in women with breast cancer who received neoadjuvant chemotherapy.

methodsWe digitised tissue sections of both diagnostic and surgical samples of breast tumours from 768 patients enrolled in the Neo-tAnGo randomized controlled trial. We subjected digital images to systematic analysis optimised for detection of single cells. Machine-learning methods were used to classify cells as cancer, stromal or lymphocyte and we computed estimates of absolute numbers, relative fractions and cell densities using these data. Pathological complete response (pCR), a histological indicator of chemotherapy response, was the primary endpoint. Fifteen image metrics were tested for their association with pCR using univariate and multivariate logistic regression.

resultsMedian lymphocyte density proved most strongly associated with pCR on univariate analysis (OR 4.46, 95 % CI 2.34-8.50, p < 0.0001; observations = 614) and on multivariate analysis (OR 2.42, 95 % CI 1.08-5.40, p = 0.03; observations = 406) after adjustment for clinical factors. Further exploratory analyses revealed that in approximately one quarter of cases there was an increase in lymphocyte density in the tumour removed at surgery compared to diagnostic biopsies. A reduction in lymphocyte density at surgery was strongly associated with pCR (OR 0.28, 95 % CI 0.17-0.47, p < 0.0001; observations = 553).

conclusionsA data-driven analysis of computational pathology reveals lymphocyte density as an independent predictor of pCR. Paradoxically an increase in lymphocyte density, following exposure to chemotherapy, is associated with a lack of pCR. Computational pathology can provide objective, quantitative and reproducible tissue metrics and represents a viable means of outcome prediction in breast cancer.

trial registrationClinicalTrials.gov NCT00070278 ; 03/10/2003.

Indexed as

AdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBiopsyBreast NeoplasmsChemotherapy, AdjuvantEpirubicinErb-b2 Receptor Tyrosine KinasesFemaleHumansLymphocytesMiddle AgedNeoadjuvant TherapyTaxoidsBiomarkers, TumorEpirubicinErb-b2 Receptor Tyrosine KinasesTaxoids

Identifiers

PMID26882907
PMCPMC4755003
OpenAlexW2279691757

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.