Evidence map›Paper›PMID 32036454›Full record

ArticleJournal of cancer research and clinical oncology2020

New HER2-negative breast cancer subtype responsive to anti-HER2 therapy identified.

Ian A MacNeil, David J Burns, Benjamin E Rich, Sajjad M Soltani, Samantha Kharbush, Nicole G Osterhaus, Brian F Sullivan, Douglas M Hawkins, Jodie R Pietruska, Lance G Laing

Open access · hybridAbstract read
In one paragraph

Article in Journal of cancer research and clinical oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 24% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

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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

10 authors at 3 institutions in 1 country.

Ian A MacNeilCelcuity Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN, 55446, USA.
David J BurnsCelcuity Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN, 55446, USA.
Benjamin E RichCelcuity Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN, 55446, USA.
Sajjad M SoltaniCelcuity Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN, 55446, USA.
Samantha KharbushCelcuity Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN, 55446, USA.
Nicole G OsterhausCelcuity Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN, 55446, USA.
Brian F SullivanCelcuity Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN, 55446, USA.
Douglas M HawkinsSchool of Statistics, University of Minnesota, Minneapolis, MN, 55455, USA.
Jodie R PietruskaDepartment of Developmental, Molecular, and Chemical Biology, Tufts University, Boston, MA, 02111, USA.
Lance G LaingCelcuity Inc., 16305 36th Ave N, Suite 100, Minneapolis, MN, 55446, USA. llaing@celcuity.com.ORCID http://orcid.org/0000-0003-4593-0685
Acuity Technologies (United States) · USTufts University · USUniversity of Minnesota · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeHER2 signaling functional activity may be important to measure in addition to HER2 protein quantification when identifying patients eligible for HER2 therapies. A HER2 Signaling Function (CELx HSF) Test for HER2-negative patients uses patient's live tumor cells on a biosensor to identify patients with abnormally high HER2-related signaling (HSFs+) likely to respond to anti-HER2 therapies.

methodsThe CELx HSF test was employed to: (1) characterize the sensitivity and specificity of the test to detect abnormal levels of HER2 signaling; (2) evaluate the inhibitory effectiveness of five different anti-HER2 therapies; (3) assess the correlation between CELx HSF test detection of abnormal HER2 signaling and response to HER2 therapy using xenograft models; and (4) confirm the prevalence of abnormal HER2 signaling amongst HER2-negative breast cancer patients (HER2-/HSFs+).

resultsHER2-/HSFs+ breast cancer patient samples were identified and showed sensitivity to five approved anti-HER2 therapies. Xenograft studies using both HER2+ and HER2- cell lines confirmed that CELx HER2 signaling status better predicts HER2 inhibitor efficacy than HER2 receptor status. In a study of 114 HER2-negative breast tumor patient samples, 27 (23.7%; 95% CI = 17-32%) had abnormal HER2 signaling (HSFs+). A ROC curve constructed with this dataset projects the CELx HSF Test would have greater than 90% sensitivity and specificity to detect the HER2-/HSFs+ patient population.

conclusionsThe CELx HSF test is a well-characterized functional biomarker assay capable of identifying dynamic HER2-driven signaling dysfunction in tumor cells from HER2-negative breast cancer patients. This test has demonstrated efficacy of various HER2 targeted therapies in live tumor cells from the HSFs+ population and correlated the test result to HER2 drug response in mouse xenograft studies. The proportion of HER2-negative breast cancer patients found to have abnormal HER2 signaling in a 114 patient sample study, 20-25%, is significant. A clinical trial to evaluate the efficacy of anti-HER2 therapies in this patient population is warranted.

Indexed as

AnimalsAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsElectric ImpedanceErb-b2 Receptor Tyrosine KinasesFemaleHumansMiceSignal TransductionXenograft Model Antitumor AssaysAntineoplastic AgentsBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesBreast cancerCell signalingHER2Targeted therapyXenograft

Identifiers

PMID32036454
PMCPMC7039866
OpenAlexW3005403004

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.