Evidence map›Paper›PMID 29768301›Full record

Trial reportPharmacogenetics and genomics2018

Germline genome-wide association studies in women receiving neoadjuvant chemotherapy with or without bevacizumab.

James N Ingle, Krishna R Kalari, Donald Lawrence Wickerham, Gunter von Minckwitz, Peter A Fasching, Yoichi Furukawa, Taisei Mushiroda, Matthew P Goetz, Poulami Barman, Erin E Carlson and 9 more

Open access · greenAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Pharmacogenetics and genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 53% 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

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Trial
  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

19 authors at 10 institutions in 6 countries.

James N IngleDepartment of Oncology.
Krishna R KalariDepartment of Health Sciences Research.
Donald Lawrence WickerhamDepartment of Human Oncology, Allegheny Health Network Cancer Institute.
Gunter von MinckwitzDepartment of Gynecology and Obstetrics, University Hospital, Frankfurt.
Peter A FaschingDepartment of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, University Hospital, Erlangen, Germany.
Yoichi FurukawaRIKEN Center for Integrative Medical Science, Yokohama, Japan.
Taisei MushirodaRIKEN Center for Integrative Medical Science, Yokohama, Japan.
Matthew P GoetzDepartment of Oncology.
Poulami BarmanDepartment of Health Sciences Research.
Erin E CarlsonDepartment of Health Sciences Research.
Priya RastogiNational Surgical Adjuvant Breast and Bowel Project (NSABP) (NSABP legacy trials are now part of the NRG Oncology portfolio).
Joseph P CostantinoNational Surgical Adjuvant Breast and Bowel Project (NSABP) (NSABP legacy trials are now part of the NRG Oncology portfolio).
Junmei CairnsDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota.
Soonmyung PaikNational Surgical Adjuvant Breast and Bowel Project (NSABP) (NSABP legacy trials are now part of the NRG Oncology portfolio).
Harry D BearNational Surgical Adjuvant Breast and Bowel Project (NSABP) (NSABP legacy trials are now part of the NRG Oncology portfolio).
Michiaki KuboRIKEN Center for Integrative Medical Science, Yokohama, Japan.
Liewei WangDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota.
Norman WolmarkDepartment of Human Oncology, Allegheny Health Network Cancer Institute.
Richard M WeinshilboumDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota.
Department of Medical Sciences · BYRIKEN Center for Integrative Medical Sciences · JPWinnMed · USNRG Oncology · USCancer Institute (WIA) · INNSABP Foundation · USUniversitätsklinikum Erlangen · DEUniversity Hospital Frankfurt · DEVirginia Commonwealth University · USYonsei University · KR

Funding

NRG Oncology Network Group Operations Center - GY9 BIQSFP Reports/BudgetsU10CA180868 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI NORMAN WOLMARK · 2014 to 2026
$206.8M
Statistics CoreU10CA180822 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Mei-Yin C Polley · 2014 to 2026
$146.4M
NRG Oncology NCORP Research Base-BIQSFPUG1CA189867 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI Deborah Watkins Bruner, Lisa A. Kachnic · 2014 to 2026
$140.5M
The Role of CHFR in Tumorigenesis and Paclitaxel-Sensitivity in Breast CancerP50CA116201 · NCI · MAYO CLINIC ROCHESTER · PI PETER C LUCAS · 2005 to 2026
$49.9M
Pharmacogenetics of Phase II Drug Metabolizing EnzymesU19GM061388 · NIGMS · MAYO CLINIC ROCHESTER · PI WEINSHILBOUM, RICHARD M. · 2010 to 2014
$15.8M
NSABP Biological Specimen BanksU24CA114732 · NCI · NSABP FOUNDATION, INC. · PI WOLMARK, NORMAN · 2005 to 2014
$9.4M
NCI NIH HHS P50 CA116201NCI NIH HHS U10 CA180822NCI NIH HHS U10 CA180868NCI NIH HHS U24 CA114732NCI NIH HHS UG1 CA189867NIGMS NIH HHS U19 GM061388
6 · The paper itself

Abstract

Neoadjuvant chemotherapy (NAC) for breast cancer is widely utilized, and we performed genome-wide association studies (GWAS) to determine whether germ-line genetic variability was associated with benefit in terms of pathological complete response (pCR), disease-free survival, and overall survival in patients entered on the NSABP B-40 NAC trial, wherein patients were randomized to receive, or not, bevacizumab in addition to chemotherapy. Patient DNA samples were genotyped with the Illumina OmniExpress BeadChip. Replication was attempted with genotyping data from 1398 HER2-negative patients entered on the GeparQuinto NAC study in which patients were also randomized to receive, or not, bevacizumab in addition to chemotherapy. A total of 920 women from B-40 were analyzed, and 237 patients achieved a pCR. GWAS with three phenotypes (pCR, disease-free survival, overall survival) revealed no single nucleotide polymorphisms (SNPs) that were genome-wide significant (i.e. P≤5E-08) signals; P values for top SNPs were 2.04E-07, 5.61E-08, and 5.63E-08, respectively, and these SNPs were not significant in the GeparQuinto data. An ad-hoc GWAS was performed in the patients randomized to bevacizumab (457 patients with 128 pCR) who showed signals on chromosome 6, located within a gene, CDKAL1, that approached, but did not reach, genome-wide significance (top SNP rs7453577, P=2.97E-07). However, this finding was significant when tested in the GeparQuinto data set (P=0.04). In conclusion, we identified no SNPs significantly associated with NAC. The observation, in a hypothesis-generating GWAS, of an SNP in CDKAL1 associated with pCR in the bevacizumab arm of both B-40 and GeparQuinto requires further validation and study.

Indexed as

AdultAgedBevacizumabBreast NeoplasmsFemaleGenome-Wide Association StudyHumansMiddle AgedNeoadjuvant TherapyPolymorphism, Single NucleotideSurvival AnalysisTreatment OutcometRNA MethyltransferasesYoung AdultBevacizumabCDKAL1 protein, humantRNA Methyltransferases

Identifiers

PMID29768301
PMCPMC5965682
OpenAlexW2804914389

What OpenQuestion holds

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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.