Evidence map›Paper›PMID 31455425›Full record

ArticleBreast cancer research : BCR2019

Addition of zoledronic acid to neoadjuvant chemotherapy is not beneficial in patients with HER2-negative stage II/III breast cancer: 5-year survival analysis of the NEOZOTAC trial (BOOG 2010-01).

Stefanie de Groot, Hanno Pijl, Ayoub Charehbili, Saskia van de Ven, Vincent T H B M Smit, Elma Meershoek-Klein Kranenbarg, Joan B Heijns, Laurence J C van Warmerdam, Lonneke W Kessels, M Wouter Dercksen and 10 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research : BCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01099436 (A Phase III Randomized Trial With NEOadjuvant Chemotherapy), which is not on this map. Cited by 5 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 2 pooled it
0.5field-weighted citation impact, top 31% 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.

NCT01099436 phase3completednot on this map

A Phase III Randomized Trial With NEOadjuvant Chemotherapy (TAC) With or Without ZOledronic Acid for Patients With HER2- Negative Large Resectable or Locally Advanced Breast Cancer(NEO-ZOTAC)

TypeinterventionalSponsorBorstkanker Onderzoek GroepRan2010 to 2013Enrolled250ConditionsBreast CancerArmscyclophosphamide, docetaxel, doxorubicin hydrochloride, zoledronic acid, neoadjuvant therapy
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 2 syntheses or guidelines pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Review
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

20 authors at 10 institutions in 1 country.

Stefanie de GrootDepartment of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, Leiden, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Hanno PijlDepartment of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
Ayoub CharehbiliDepartment of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, Leiden, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Saskia van de VenDepartment of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands.
Vincent T H B M SmitDepartment of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Elma Meershoek-Klein KranenbargDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Joan B HeijnsDepartment of Medical Oncology, Amphia hospital, Breda, The Netherlands.
Laurence J C van WarmerdamDepartment of Clinical Oncology, Catharina Ziekenhuis, Eindhoven, The Netherlands.
Lonneke W KesselsDepartment of Medical Oncology, Deventer hospital, Deventer, The Netherlands.
M Wouter DercksenDepartment of Clinical Oncology, Maxima Medisch Centrum, Veldhoven, The Netherlands.
Manon J A E PepelsDepartment of Clinical Oncology, Elkerliek Ziekenhuis, Helmond, The Netherlands.
Hanneke W M van LaarhovenDepartment of Medical Oncology, Cancer Center Amsterdam, Amsterdam Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Birgit E P J VriensDepartment of Clinical Oncology, Catharina Ziekenhuis, Eindhoven, The Netherlands.
Hein PutterDepartment of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
Marta FioccoDepartment of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
Gerrit-Jan LiefersDepartment of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Jacobus J M van der HoevenDepartment of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, Leiden, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Johan W R NortierDepartment of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, Leiden, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Judith R KroepDepartment of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, Leiden, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. j.r.kroep@lumc.nl.
Dutch Breast Cancer Research Group
Leiden University Medical Center · NLRadboud University Nijmegen · NLAmphia Ziekenhuis · NLCatharina Ziekenhuis · NLDeventer Ziekenhuis · NLElkerliek Ziekenhuis · NLMáxima Medisch Centrum · NLUniversity Medical Center Utrecht · NLUniversity of Amsterdam · NLUniversity of Applied Sciences Leiden · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAdjuvant bisphosphonates are associated with improved breast cancer survival in postmenopausal patients. Addition of zoledronic acid (ZA) to neoadjuvant chemotherapy did not improve pathological complete response in the phase III NEOZOTAC trial. Here we report the results of the secondary endpoints, disease-free survival, (DFS) and overall survival (OS). PATIENTS AND

methodsPatients with HER2-negative, stage II/III breast cancer were randomized to receive the standard 6 cycles of neoadjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy with or without 4 mg intravenous (IV) ZA administered within 24 h of chemotherapy. This was repeated every 21 days for 6 cycles. Cox regression models were used to evaluate the effect of ZA and covariates on DFS and OS. Regression models were used to examine the association between insulin, glucose, insulin growth factor-1 (IGF-1) levels, and IGF-1 receptor (IGF-1R) expression with survival outcomes.

resultsTwo hundred forty-six women were eligible for inclusion. After a median follow-up of 6.4 years, OS for all patients was significantly worse for those who received ZA (HR 0.468, 95% CI 0.226-0.967, P = 0.040). DFS was not significantly different between the treatment arms (HR 0.656, 95% CI 0.371-1.160, P = 0.147). In a subgroup analysis of postmenopausal women, no significant difference in DFS or OS was found for those who received ZA compared with the control group (HR 0.464, 95% CI 0.176-1.222, P = 0.120; HR 0.539, 95% CI 0.228-1.273, P = 0.159, respectively). The subgroup analysis of premenopausal patients was not significantly different for DFS and OS ((HR 0.798, 95% CI 0.369-1.725, P = 0.565; HR 0.456, 95% CI 0.156-1.336, P = 0.152, respectively). Baseline IGF-1R expression was not significantly associated with DFS or OS. In a predefined additional study, lower serum levels of insulin were associated with improved DFS (HR 1.025, 95% CI 1.005-1.045, P = 0.014).

conclusionsOur results suggest that ZA in combination with neoadjuvant chemotherapy was associated with a worse OS in breast cancer (both pre- and postmenopausal patients). However, in a subgroup analysis of postmenopausal patients, ZA treatment was not associated with DFS or OS. Also, DFS was not significantly different between both groups. IGF-1R expression in tumor tissue before and after neoadjuvant treatment did not predict survival.

trial registrationClinicalTrials.gov, NCT01099436 , April 2010.

Indexed as

AdultAgedAntineoplastic Combined Chemotherapy ProtocolsBone Density Conservation AgentsBreast NeoplasmsClinical Trials, Phase III as TopicErb-b2 Receptor Tyrosine KinasesFemaleHumansInsulinInsulin-Like Growth Factor IMenopauseMiddle AgedNeoadjuvant TherapyReceptor, IGF Type 1Survival AnalysisBone Density Conservation AgentsERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesIGF1 protein, humanIGF1R protein, humanInsulinInsulin-Like Growth Factor IReceptor, IGF Type 1Zoledronic AcidBreast cancerIGF-1RInsulinNeoadjuvant chemotherapySurvivalZoledronic acid

Identifiers

PMID31455425
PMCPMC6712613
OpenAlexW2970869419

What OpenQuestion holds

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LicenceCC BY
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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.