Evidence map›Paper›PMID 29338072›Full record

ArticleCancer2018

Targeting HER2 in colorectal cancer: The landscape of amplification and short variant mutations in ERBB2 and ERBB3.

Jeffrey S Ross, Marwan Fakih, Siraj M Ali, Julia A Elvin, Alexa B Schrock, James Suh, Jo-Anne Vergilio, Shakti Ramkissoon, Eric Severson, Sugganth Daniel and 6 more

Open access · hybridAbstract read
In one paragraph

Article in Cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
119citing papers in PubMed, 3 pooled it
7.2field-weighted citation impact, top 2% 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

119 citing papers in PubMed, 3 syntheses or guidelines pooled it, 203 citations in OpenAlex.

  1. Pooled it
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  14. Advances in Targeting HER2 across Cancer Subtypes: A Pan-Tumor Approach.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Review
  15. Review
  16. Article
  17. Article
  18. HER2-targeted therapy in colorectal cancer: a comprehensive review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Review
  19. Article
  20. Article

59 more citing papers are in PubMed but not listed here.

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

16 authors at 2 institutions in 1 country.

Jeffrey S RossFoundation Medicine Inc, Cambridge, Massachusetts.
Marwan FakihDepartment of Medical Oncology and Therapeutics Research City of Hope, Duarte, California.
Siraj M AliFoundation Medicine Inc, Cambridge, Massachusetts.
Julia A ElvinFoundation Medicine Inc, Cambridge, Massachusetts.
Alexa B SchrockFoundation Medicine Inc, Cambridge, Massachusetts.
James SuhFoundation Medicine Inc, Cambridge, Massachusetts.
Jo-Anne VergilioFoundation Medicine Inc, Cambridge, Massachusetts.
Shakti RamkissoonFoundation Medicine Inc, Cambridge, Massachusetts.
Eric SeversonFoundation Medicine Inc, Cambridge, Massachusetts.
Sugganth DanielFoundation Medicine Inc, Cambridge, Massachusetts.
David FabrizioFoundation Medicine Inc, Cambridge, Massachusetts.
Garrett FramptonFoundation Medicine Inc, Cambridge, Massachusetts.
James SunFoundation Medicine Inc, Cambridge, Massachusetts.
Vincent A MillerFoundation Medicine Inc, Cambridge, Massachusetts.
Philip J StephensFoundation Medicine Inc, Cambridge, Massachusetts.
Laurie M GayFoundation Medicine Inc, Cambridge, Massachusetts.ORCID 0000-0003-2022-6130
Foundation Medicine (United States)City of Hope · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn contrast to lung cancer, few precision treatments are available for colorectal cancer (CRC). One rapidly emerging treatment target in CRC is ERBB2 (human epidermal growth factor receptor 2 [HER2]). Oncogenic alterations in HER2, or its dimerization partner HER3, can underlie sensitivity to HER2-targeted therapies.

methodsIn this study, 8887 CRC cases were evaluated by comprehensive genomic profiling for genomic alterations in 315 cancer-related genes, tumor mutational burden, and microsatellite instability. This cohort included both colonic (7599 cases; 85.5%) and rectal (1288 cases; 14.5%) adenocarcinomas.

resultsA total of 569 mCRCs were positive for ERBB2 (429 cases; 4.8%) and/or ERBB3 (148 cases; 1.7%) and featured ERBB amplification, short variant alterations, or a combination of the 2. High tumor mutational burden (≥20 mutations/Mb) was significantly more common in ERBB-mutated samples, and ERBB3-mutated CRCs were significantly more likely to have high microsatellite instability (P<.002). Alterations affecting KRAS (27.3%) were significantly underrepresented in ERBB2-amplified samples compared with wild-type CRC samples (51.8%), and ERBB2- or ERBB3-mutated samples (49.0% and 60.8%, respectively) (P<.01). Other significant differences in mutation frequency were observed for genes in the PI3K/MTOR and mismatch repair pathways.

conclusionsAlthough observed less often than in breast or upper gastrointestinal carcinomas, indications for which anti-HER2 therapies are approved, the percentage of CRC with ERBB genomic alterations is significant. Importantly, 32% of ERBB2-positive CRCs harbor short variant alterations that are undetectable by routine immunohistochemistry or fluorescence in situ hybridization testing. The success of anti-HER2 therapies in ongoing clinical trials is a promising development for patients with CRC. Cancer 2018;124:1358-73. © 2018 Foundation Medicine, Inc. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Indexed as

Gene AmplificationMolecular Targeted TherapyMutationAdolescentAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorChildColorectal NeoplasmsErb-b2 Receptor Tyrosine KinasesFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticGenomicsBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesERBB3 protein, humanReceptor, ErbB-3colorectal adenocarcinomacomprehensive genomic profilingERBB2, ERBB3human epidermal growth factor receptor 2 (HER2)lapatinibmicrosatellite instabilitypertuzumabtrastuzumabtumor mutational burden

Identifiers

PMID29338072
PMCPMC5900732
OpenAlexW2784265898

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.