Evidence map›Paper›PMID 27602761›Full record

ArticleOncotarget2016

ctDNA dynamics: a novel indicator to track resistance in metastatic breast cancer treated with anti-HER2 therapy.

Fei Ma, Wenjie Zhu, Yanfang Guan, Ling Yang, Xuefeng Xia, Shanshan Chen, Qiao Li, Xiuwen Guan, Zongbi Yi, Haili Qian and 2 more

Registry-linked trialOpen access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01937689 (A Phase I Study of Pyrotinib in Patients With HER2 Positive Advanced Breast Cancer), which is not on this map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 7% 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.

NCT01937689 phase1completednot on this map

A Phase I Study of Pyrotinib in Patients With HER2 Positive Advanced Breast Cancer

TypeinterventionalSponsorJiangsu HengRui Medicine Co., Ltd.Ran2013 to 2016Enrolled40ConditionsBreast CancerArmsPyrotinib
3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Clinical impact of intratumoral HER2 heterogeneity on trastuzumab deruxtecan efficacy in patients with HER2-positive gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026
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  12. Article
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  15. The journal of liquid biopsy · 2023
    Review
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  18. Imaging in metastatic breast cancer, CT, PET/CT, MRI, WB-DWI, CCA: review and new perspectives.Cancer imaging : the official publication of the International Cancer Imaging Society · 2023
    Review
  19. Review
  20. 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

12 authors at 2 institutions in 2 countries.

Fei MaDepartment of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Wenjie ZhuDepartment of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yanfang GuanGeneplus-Beijing, Beijing, China.
Ling YangGeneplus-Beijing, Beijing, China.
Xuefeng XiaHouston Methodist Research Institute, Weill Cornell School of Medicine, Houston, TX, USA.
Shanshan ChenDepartment of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Qiao LiDepartment of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Xiuwen GuanDepartment of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Zongbi YiDepartment of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Haili QianState Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Xin YiGeneplus-Beijing, Beijing, China.
Binghe XuDepartment of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Chinese Academy of Medical Sciences & Peking Union Medical College · CNMethodist Hospital · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMost studies utilizing circulating tumor DNA (ctDNA) to monitor disease interrogated only one or a few genes and failed to develop workable criteria to inform clinical practice. We evaluated the feasibility of detecting resistance to anti-HER2 therapy by serial gene-panel ctDNA sequencing.

resultsPrimary therapeutic resistance was identified in 6 out of 14 patients with events of progressive disease. For this subset comparison of pre- and post-treatment ctDNA assay results revealed that HER2 amplification concurred with disease progression (4/6, 66.7%). Mutations in TP53 (3/6, 50.0%) and genes implicated in the PI3K/mTOR pathway (3/6, 50.0%) were also dominant markers of resistance. Together, resistance to HER2 blockade should be indicated during treatment if any of the following situations applies: 1) recurrence or persistence of HER2 amplification in the blood; 2) emergence or ≥20% increase in the fraction of mutations in any of these resistance-related genes including TP53/PIK3CA/MTOR/PTEN. Compared with CT scans, dynamic ctDNA profiling utilizing pre-defined criteria was sensitive in identifying drug resistance (sensitivity 85.7%, specificity 55.0%), with a concordance rate up to 82.1%. Besides, the ctDNA criteria had a discriminating role in the prognosis of HER2-positive metastatic breast cancer.

methods52 plasma samples were prospectively collected from 18 patients with HER2-positive metastatic breast cancer who were treated with an oral anti-HER1/HER2 tyrosine kinase inhibitor (ClinicalTrials.gov NCT01937689). ctDNA was assayed by gene-panel target-capture next-generation sequencing.

conclusionsLongitudinal gene-panel ctDNA sequencing could be exploited to determine resistance and guide the precise administration of anti-HER2 targeted therapy in the metastatic setting.

Indexed as

AcrylamidesAminoquinolinesBiomarkers, TumorBreast NeoplasmsCase-Control StudiesCirculating Tumor DNAClass I Phosphatidylinositol 3-KinasesDNA, NeoplasmDrug Resistance, NeoplasmErb-b2 Receptor Tyrosine KinasesFemaleFollow-Up StudiesHumansMutationPrognosisProspective StudiesAcrylamidesAminoquinolinesBiomarkers, TumorCirculating Tumor DNAClass I Phosphatidylinositol 3-KinasesDNA, NeoplasmERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesPIK3CA protein, humanPTEN PhosphohydrolasePTEN protein, humanpyrotinibTOR Serine-Threonine Kinasesanti-HER2 therapycirculating tumor DNAdynamicsmetastatic breast cancerprogression

Identifiers

PMID27602761
PMCPMC5323211
OpenAlexW2514009911

What OpenQuestion holds

Textmetadata
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.