Evidence map›Paper›PMID 23035882›Full record

ArticleBMC medical genomics2012

PAM50 breast cancer subtyping by RT-qPCR and concordance with standard clinical molecular markers.

Roy R L Bastien, Álvaro Rodríguez-Lescure, Mark T W Ebbert, Aleix Prat, Blanca Munárriz, Leslie Rowe, Patricia Miller, Manuel Ruiz-Borrego, Daniel Anderson, Bradley Lyons and 22 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in BMC medical genomics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00129922 (Phase III Study to Compare 6 Courses of FEC), which is not on this map. Cited by 181 papers.

0numbers the graph read from it
0cells of the map it votes in
181citing papers in PubMed
13.2field-weighted citation impact, top 1% 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.

NCT00129922 phase3completednot on this map

Phase III Study to Compare 6 Courses of FEC (Fluorouracil, Epirubicin and Cyclophosphamide) vs. 4 Courses of FEC Followed by 8 Weekly Paclitaxel Administrations, as Adjuvant Treatment for Node Positive Operable BC Patients

TypeinterventionalSponsorSpanish Breast Cancer Research GroupRan1999 to 2007Enrolled1,289ConditionsBreast CancerArmspaclitaxel, Fluorouracil, Epirubicin, Cyclophosphamide
3 · Its place in the literature

Who cites it

181 citing papers in PubMed, 340 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Bioinformatic Approach to Identify Positive PrognosticInternational journal of molecular sciences · 2025
    Article
  12. Article
  13. Article
  14. Article
  15. Assessment ofHealth science reports · 2025
    Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

121 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

32 authors at 17 institutions in 3 countries.

Roy R L BastienThe ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, USA.
Álvaro Rodríguez-Lescure
Mark T W Ebbert
Aleix Prat
Blanca Munárriz
Leslie Rowe
Patricia Miller
Manuel Ruiz-Borrego
Daniel Anderson
Bradley Lyons
Isabel Álvarez
Tracy Dowell
David Wall
Miguel Ángel Seguí
Lee Barley
Kenneth M Boucher
Emilio Alba
Lisa Pappas
Carole A Davis
Ignacio Aranda
Christiane Fauron
Inge J Stijleman
José Palacios
Antonio Antón
Eva Carrasco
Rosalía Caballero
Matthew J Ellis
Torsten O Nielsen
Charles M Perou
Mark Astill
Philip S Bernard
Miguel Martín
ARUP Laboratories (United States) · USARUP Institute for Clinical and Experimental PathologyHuntsman Cancer Institute · USGEICAM – Spanish Breast Cancer Group · ESHospital Universitario Virgen del Rocío · ESUniversity of North Carolina at Chapel Hill · USBiogipuzkoa Health Research Institute · ESCorporació Sanitària Parc Taulí · ESHospital Clínico Universitario Virgen de la Victoria · ESHospital General Universitario de Alicante Doctor Balmis · ESHospital General Universitario de Elche · ESHospital General Universitario Gregorio Marañón · ESHospital Universitari i Politècnic La Fe · ESHospital Universitario Miguel Servet · ESUniversity of British Columbia · CAUniversity of Utah · USWashington University in St. Louis · US

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI CORNELIA M ULRICH · 1986 to 2026
$72.6M
Biological Breast Cancer Classification by qRT-PCRU01CA114722 · NCI · WASHINGTON UNIVERSITY · PI ELLIS, MATTHEW J · 2005 to 2009
$8.7M
NCI NIH HHS P30 CA42014-19NCI NIH HHS U01 CA114722NCI NIH HHS U01 CA114722-01
6 · The paper itself

Abstract

backgroundMany methodologies have been used in research to identify the "intrinsic" subtypes of breast cancer commonly known as Luminal A, Luminal B, HER2-Enriched (HER2-E) and Basal-like. The PAM50 gene set is often used for gene expression-based subtyping; however, surrogate subtyping using panels of immunohistochemical (IHC) markers are still widely used clinically. Discrepancies between these methods may lead to different treatment decisions.

methodsWe used the PAM50 RT-qPCR assay to expression profile 814 tumors from the GEICAM/9906 phase III clinical trial that enrolled women with locally advanced primary invasive breast cancer. All samples were scored at a single site by IHC for estrogen receptor (ER), progesterone receptor (PR), and Her2/neu (HER2) protein expression. Equivocal HER2 cases were confirmed by chromogenic in situ hybridization (CISH). Single gene scores by IHC/CISH were compared with RT-qPCR continuous gene expression values and "intrinsic" subtype assignment by the PAM50. High, medium, and low expression for ESR1, PGR, ERBB2, and proliferation were selected using quartile cut-points from the continuous RT-qPCR data across the PAM50 subtype assignments.

resultsESR1, PGR, and ERBB2 gene expression had high agreement with established binary IHC cut-points (area under the curve (AUC) ≥ 0.9). Estrogen receptor positivity by IHC was strongly associated with Luminal (A and B) subtypes (92%), but only 75% of ER negative tumors were classified into the HER2-E and Basal-like subtypes. Luminal A tumors more frequently expressed PR than Luminal B (94% vs 74%) and Luminal A tumors were less likely to have high proliferation (11% vs 77%). Seventy-seven percent (30/39) of ER-/HER2+ tumors by IHC were classified as the HER2-E subtype. Triple negative tumors were mainly comprised of Basal-like (57%) and HER2-E (30%) subtypes. Single gene scoring for ESR1, PGR, and ERBB2 was more prognostic than the corresponding IHC markers as shown in a multivariate analysis.

conclusionsThe standard immunohistochemical panel for breast cancer (ER, PR, and HER2) does not adequately identify the PAM50 gene expression subtypes. Although there is high agreement between biomarker scoring by protein immunohistochemistry and gene expression, the gene expression determinations for ESR1 and ERBB2 status was more prognostic.

Indexed as

Biomarkers, TumorBreastBreast NeoplasmsCell Line, TumorCell ProliferationClinical Trials as TopicCluster AnalysisErb-b2 Receptor Tyrosine KinasesEstrogen Receptor alphaFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryKaplan-Meier EstimateLimit of DetectionMultivariate AnalysisBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesESR1 protein, humanEstrogen Receptor alphaRNA, Messenger

Identifiers

PMID23035882
PMCPMC3487945
OpenAlexW2119434445

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.