Evidence map›Paper›PMID 25139534›Full record

ArticleJournal of the National Cancer Institute2014

Molecular features and survival outcomes of the intrinsic subtypes within HER2-positive breast cancer.

Aleix Prat, Lisa A Carey, Barbara Adamo, Maria Vidal, Josep Tabernero, Javier Cortés, Joel S Parker, Charles M Perou, José Baselga

Registry-linked trialOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the National Cancer Institute, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03272477 (A Prospective, Randomized, Multicenter, Open-label Comparison of Pre-surgical Combination of Trastuzumab and Pertuzumab With Concurrent Taxane Chemotherapy or Endocrine Therapy Given for Twelve Weeks With a Quality of Life Assessment of Trastuzumab, Pertuzumab in Combination With Standard), which is not on this map. Cited by 127 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
127citing papers in PubMed, 3 pooled it
8.2field-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.

NCT03272477 phase2completednot on this mapstarted 2017, after this paper: background citation

A Prospective, Randomized, Multicenter, Open-label Comparison of Pre-surgical Combination of Trastuzumab and Pertuzumab With Concurrent Taxane Chemotherapy or Endocrine Therapy Given for Twelve Weeks With a Quality of Life Assessment of Trastuzumab, Pertuzumab in Combination With Standard (Neo)Adjuvant Treatment in Patients With Operable HER2+/HR+ Breast Cancer.

TypeinterventionalSponsorPalleos Healthcare GmbHRan2017 to 2024Enrolled257ConditionsBreast NeoplasmsArmsPerjeta Injectable Product, Herceptin, Tamoxifen, Paclitaxel, Epirubicin
3 · Its place in the literature

Who cites it

127 citing papers in PubMed, 3 syntheses or guidelines pooled it, 224 citations in OpenAlex.

  1. Pooled it
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  4. Adjuvant Dose-Dense Chemotherapy in Hormone Receptor-Positive Breast Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025
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  9. Correlative Biomarker Analysis of Intrinsic Subtypes and Efficacy Across the MONALEESA Phase III Studies.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021
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  14. A PAM50-Based Chemoendocrine Score for Hormone Receptor-Positive Breast Cancer with an Intermediate Risk of Relapse.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017
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67 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

9 authors at 2 institutions in 1 country.

Aleix Prat: Breast Cancer Unit (AP, BA, MV, JC), Department of Medical Oncology (AP, BA, MV, JC, JT), and Translational Genomics Group (AP, MV), Vall d'Hebron Institute of Oncology Barcelona, Spain; Lineberger Comprehensive Cancer Center (LAC, JSP, CMP), Department of Genetics (CMP), and Department of Pathology and Laboratory Medicine (CMP), University of North Carolina, Chapel Hill, NC; Memorial Sloan-Kettering Cancer Center, New York (JB). aprat@vhio.net.
Lisa A Carey: Breast Cancer Unit (AP, BA, MV, JC), Department of Medical Oncology (AP, BA, MV, JC, JT), and Translational Genomics Group (AP, MV), Vall d'Hebron Institute of Oncology Barcelona, Spain; Lineberger Comprehensive Cancer Center (LAC, JSP, CMP), Department of Genetics (CMP), and Department of Pathology and Laboratory Medicine (CMP), University of North Carolina, Chapel Hill, NC; Memorial Sloan-Kettering Cancer Center, New York (JB).
Barbara Adamo: Breast Cancer Unit (AP, BA, MV, JC), Department of Medical Oncology (AP, BA, MV, JC, JT), and Translational Genomics Group (AP, MV), Vall d'Hebron Institute of Oncology Barcelona, Spain; Lineberger Comprehensive Cancer Center (LAC, JSP, CMP), Department of Genetics (CMP), and Department of Pathology and Laboratory Medicine (CMP), University of North Carolina, Chapel Hill, NC; Memorial Sloan-Kettering Cancer Center, New York (JB).
Maria Vidal: Breast Cancer Unit (AP, BA, MV, JC), Department of Medical Oncology (AP, BA, MV, JC, JT), and Translational Genomics Group (AP, MV), Vall d'Hebron Institute of Oncology Barcelona, Spain; Lineberger Comprehensive Cancer Center (LAC, JSP, CMP), Department of Genetics (CMP), and Department of Pathology and Laboratory Medicine (CMP), University of North Carolina, Chapel Hill, NC; Memorial Sloan-Kettering Cancer Center, New York (JB).
Josep Tabernero: Breast Cancer Unit (AP, BA, MV, JC), Department of Medical Oncology (AP, BA, MV, JC, JT), and Translational Genomics Group (AP, MV), Vall d'Hebron Institute of Oncology Barcelona, Spain; Lineberger Comprehensive Cancer Center (LAC, JSP, CMP), Department of Genetics (CMP), and Department of Pathology and Laboratory Medicine (CMP), University of North Carolina, Chapel Hill, NC; Memorial Sloan-Kettering Cancer Center, New York (JB).
Javier Cortés: Breast Cancer Unit (AP, BA, MV, JC), Department of Medical Oncology (AP, BA, MV, JC, JT), and Translational Genomics Group (AP, MV), Vall d'Hebron Institute of Oncology Barcelona, Spain; Lineberger Comprehensive Cancer Center (LAC, JSP, CMP), Department of Genetics (CMP), and Department of Pathology and Laboratory Medicine (CMP), University of North Carolina, Chapel Hill, NC; Memorial Sloan-Kettering Cancer Center, New York (JB).
Joel S Parker: Breast Cancer Unit (AP, BA, MV, JC), Department of Medical Oncology (AP, BA, MV, JC, JT), and Translational Genomics Group (AP, MV), Vall d'Hebron Institute of Oncology Barcelona, Spain; Lineberger Comprehensive Cancer Center (LAC, JSP, CMP), Department of Genetics (CMP), and Department of Pathology and Laboratory Medicine (CMP), University of North Carolina, Chapel Hill, NC; Memorial Sloan-Kettering Cancer Center, New York (JB).
Charles M Perou: Breast Cancer Unit (AP, BA, MV, JC), Department of Medical Oncology (AP, BA, MV, JC, JT), and Translational Genomics Group (AP, MV), Vall d'Hebron Institute of Oncology Barcelona, Spain; Lineberger Comprehensive Cancer Center (LAC, JSP, CMP), Department of Genetics (CMP), and Department of Pathology and Laboratory Medicine (CMP), University of North Carolina, Chapel Hill, NC; Memorial Sloan-Kettering Cancer Center, New York (JB).
José Baselga: Breast Cancer Unit (AP, BA, MV, JC), Department of Medical Oncology (AP, BA, MV, JC, JT), and Translational Genomics Group (AP, MV), Vall d'Hebron Institute of Oncology Barcelona, Spain; Lineberger Comprehensive Cancer Center (LAC, JSP, CMP), Department of Genetics (CMP), and Department of Pathology and Laboratory Medicine (CMP), University of North Carolina, Chapel Hill, NC; Memorial Sloan-Kettering Cancer Center, New York (JB).
University of North Carolina at Chapel Hill · USUNC Lineberger Comprehensive Cancer Center

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5M
Tissue Procurement & PathologyP50CA058223 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CHARLES M PEROU · 1992 to 2026
$59.3M
NCI NIH HHS P30 CA016086NCI NIH HHS P50 CA058223NCI NIH HHS P50-CA58223
6 · The paper itself

Abstract

backgroundThe clinical impact of the biological heterogeneity within HER2-positive (HER2+) breast cancer is not fully understood. Here, we evaluated the molecular features and survival outcomes of the intrinsic subtypes within HER2+ breast cancer.

methodsWe interrogated The Cancer Genome Atlas (n = 495) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets (n = 1730) of primary breast cancers for molecular data derived from DNA, RNA and protein, and determined intrinsic subtype. Clinical HER2 status was defined according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines or DNA copy-number aberration by single nucleotide polymorphism arrays. Cox models tested the prognostic significance of each variable in patients not treated with trastuzumab (n = 1711).

resultsCompared with clinically HER2 (cHER2)-negative breast cancer, cHER2+ breast cancer had a higher frequency of the HER2-enriched (HER2E) subtype (47.0% vs 7.1%) and a lower frequency of Luminal A (10.7% vs 39.0%) and Basal-like (14.1% vs 23.4%) subtypes. The likelihood of cHER2-positivity in HER2E, Luminal B, Basal-like and Luminal A subtypes was 64.6%, 20.0%, 14.4% and 7.3%, respectively. Within each subtype, only 0.3% to 3.9% of genes were found differentially expressed between cHER2+ and cHER2-negative tumors. Within cHER2+ tumors, HER2 gene and protein expression was statistically significantly higher in the HER2E and Basal-like subtypes than either luminal subtype. Neither cHER2 status nor the new 10-subtype copy number-based classification system (IntClust) added independent prognostic value to intrinsic subtype.

conclusionsWhen the intrinsic subtypes are taken into account, cHER2-positivity does not translate into large changes in the expression of downstream signaling pathways, nor does it affect patient survival in the absence of HER2 targeting.

Indexed as

DNA Copy Number VariationsPolymorphism, Single NucleotideAdultAgedAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsConfounding Factors, EpidemiologicErb-b2 Receptor Tyrosine KinasesFemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMiddle AgedMolecular Targeted TherapySignal TransductionAntineoplastic AgentsBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine Kinases

Identifiers

PMID25139534
PMCPMC4151853
OpenAlexW2144442992

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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.