Evidence map›Paper›PMID 26422389›Full record

ArticleMolecular oncology2016

High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti-HER2 therapy.

Paolo Nuciforo, Sheeno Thyparambil, Claudia Aura, Ana Garrido-Castro, Marta Vilaro, Vicente Peg, José Jimenez, Rocio Vicario, Fabiola Cecchi, William Hoos and 7 more

Open access · hybridAbstract read
In one paragraph

Article in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the 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
4.5field-weighted citation impact, top 4% 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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Ado-Trastuzumab Emtansine for Patients With HER2-Mutant Lung Cancers: Results From a Phase II Basket Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018
    Trial
  4. Review
  5. Observational
  6. Article
  7. Predictive Biomarkers of Antibody-Drug Conjugate Efficacy for Solid Tumors: Current Challenges and the Potential Role of Quantitative Proteomics.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Clinical Proteomics for Solid Organ Tissues.Molecular & cellular proteomics : MCP · 2023
    Article
  13. Review
  14. Review
  15. FISH Diagnostic Assessment ofInternational journal of molecular sciences · 2023
    Article
  16. Review
  17. Article
  18. Review
  19. Article
  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

17 authors at 5 institutions in 2 countries.

Paolo Nuciforo *Molecular Oncology Laboratory, Vall d'Hebron Institute of Oncology, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Sheeno Thyparambil *OncoPlex Diagnostics (Division of NantOmics, LLC), 9600 Medical Center Drive, Suite 300, Rockville, MD 20850, USA.
Claudia AuraMolecular Oncology Laboratory, Vall d'Hebron Institute of Oncology, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Ana Garrido-CastroDepartment of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Marta VilaroMolecular Oncology Laboratory, Vall d'Hebron Institute of Oncology, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Vicente PegDepartment of Pathology, Vall d'Hebron University Hospital, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
José JimenezMolecular Oncology Laboratory, Vall d'Hebron Institute of Oncology, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Rocio VicarioPreclinical Research Program, Vall d'Hebron Institute of Oncology, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Fabiola CecchiOncoPlex Diagnostics (Division of NantOmics, LLC), 9600 Medical Center Drive, Suite 300, Rockville, MD 20850, USA.
William HoosOncoPlex Diagnostics (Division of NantOmics, LLC), 9600 Medical Center Drive, Suite 300, Rockville, MD 20850, USA.
Jon BurrowsOncoPlex Diagnostics (Division of NantOmics, LLC), 9600 Medical Center Drive, Suite 300, Rockville, MD 20850, USA.
Todd HembroughOncoPlex Diagnostics (Division of NantOmics, LLC), 9600 Medical Center Drive, Suite 300, Rockville, MD 20850, USA.
Juan Carles FerreresDepartment of Pathology, Vall d'Hebron University Hospital, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
José Perez-GarciaDepartment of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Joaquin ArribasPreclinical Research Program, Vall d'Hebron Institute of Oncology, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Javier CortesDepartment of Oncology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Passeig Vall d'Hebron 119-129, 08035 Barcelona, Spain.
Maurizio ScaltritiHuman Oncology & Pathogenesis Program (HOPP), Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 20, New York, NY 10065, USA.
OncoPlex Diagnostics (United States) · USVall d'Hebron Hospital Universitari · ESVall d'Hebron Institute of OncologyMemorial Sloan Kettering Cancer Center · USVall d'Hebron Institut de Recerca · ES

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

introductionCurrent methods to determine HER2 (human epidermal growth factor receptor 2) status are affected by reproducibility issues and do not reliably predict benefit from anti-HER2 therapy. Quantitative measurement of HER2 may more accurately identify breast cancer (BC) patients who will respond to anti-HER2 treatments.

methodsUsing selected reaction monitoring mass spectrometry (SRM-MS), we quantified HER2 protein levels in formalin-fixed, paraffin-embedded (FFPE) tissue samples that had been classified as HER2 0, 1+, 2+ or 3+ by immunohistochemistry (IHC). Receiver operator curve (ROC) analysis was conducted to obtain optimal HER2 protein expression thresholds predictive of HER2 status (by standard IHC or in situ hybridization [ISH]) and of survival benefit after anti-HER2 therapy.

resultsAbsolute HER2 amol/μg levels were significantly correlated with both HER2 IHC and amplification status by ISH (p < 0.0001). A HER2 threshold of 740 amol/μg showed an agreement rate of 94% with IHC and ISH standard HER2 testing (p < 0.0001). Discordant cases (SRM-MS-negative/ISH-positive) showed a characteristic amplification pattern known as double minutes. HER2 levels >2200 amol/μg were significantly associated with longer disease-free survival (DFS) and overall survival (OS) in an adjuvant setting and with longer OS in a metastatic setting.

conclusionQuantitative HER2 measurement by SRM-MS is superior to IHC and ISH in predicting outcome after treatment with anti-HER2 therapy.

Indexed as

Antibodies, Monoclonal, HumanizedBreast NeoplasmsErb-b2 Receptor Tyrosine KinasesFemaleHumansLapatinibMass SpectrometryQuinazolinesSurvival AnalysisTrastuzumabAntibodies, Monoclonal, HumanizedERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesLapatinibpertuzumabQuinazolinesTrastuzumabBreast cancerHER2ImmunohistochemistryIn situ hybridizationMass spectrometryTrastuzumab

Identifiers

PMID26422389
PMCPMC4968773
OpenAlexW2196002378

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.