Evidence map›Paper›PMID 31037288›Full record

ArticleJournal of the National Cancer Institute2020

HER2-Enriched Subtype and ERBB2 Expression in HER2-Positive Breast Cancer Treated with Dual HER2 Blockade.

Aleix Prat, Tomás Pascual, Carmine De Angelis, Carolina Gutierrez, Antonio Llombart-Cussac, Tao Wang, Javier Cortés, Brent Rexer, Laia Paré, Andres Forero and 25 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of the National Cancer Institute, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 4 pooled it
8.6field-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

93 citing papers in PubMed, 4 syntheses or guidelines pooled it, 164 citations in OpenAlex.

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  11. NSABP B-41, a Randomized Neoadjuvant Trial: Genes and Signatures Associated with Pathologic Complete Response.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
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33 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

35 authors at 16 institutions in 4 countries.

Aleix PratDepartment of Medical Oncology, Hospital Clínic de Barcelona, Spain.
Tomás PascualDepartment of Medical Oncology, Hospital Clínic de Barcelona, Spain.
Carmine De AngelisDan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX.
Carolina GutierrezDan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX.
Antonio Llombart-CussacDepartment of Medical Oncology, Hospital Arnau de Vilanova, Valencia, Spain.
Tao WangDan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX.
Javier CortésIOB Institute of Oncology, Quironsalud Group, Madrid & Barcelona, Spain.
Brent RexerDepartment of Medicine, Vanderbilt University, Nashville, TN.
Laia ParéDepartment of Medical Oncology, Hospital Clínic de Barcelona, Spain.
Andres ForeroDepartment of Medicine, University of Alabama-Birmingham, Birmingham, AL.
Antonio C WolffJohns Hopkins University, Baltimore, MD.
Serafín MoralesDepartment of Medical Oncology, Hospital Universitari Arnau Vilanova, Lleida, Spain.
Barbara AdamoDepartment of Medical Oncology, Hospital Clínic de Barcelona, Spain.
Fara Brasó-MaristanyDepartment of Medical Oncology, Hospital Clínic de Barcelona, Spain.
Maria VidalDepartment of Medical Oncology, Hospital Clínic de Barcelona, Spain.
Jamunarani VeeraraghavanDan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX.
Ian KropDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA.
Patricia GalvánDepartment of Medical Oncology, Hospital Clínic de Barcelona, Spain.
Anne C PavlickDan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX.
Begoña BermejoDepartment of Medical Oncology, Hospital Clínico de Valencia, Valencia, Spain.
Miguel IzquierdoNovartis Oncology, Basel, Switzerland.
Vanessa Rodrik-OutmezguineNovartis Oncology, Basel, Switzerland.
Jorge S Reis-FilhoDepartment of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
Susan G HilsenbeckDan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX.
Mafalda OliveiraBreast Cancer Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Maria Vittoria DieciDepartment of Genetics, University of North Carolina, Chapel Hill, NC.
Gaia GriguoloDepartment of Genetics, University of North Carolina, Chapel Hill, NC.
Roberta FasaniBreast Cancer Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Paolo NuciforoBreast Cancer Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Joel S ParkerDepartment of Genetics, University of North Carolina, Chapel Hill, NC.
PierFranco ConteDepartment of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
Rachel SchiffDan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX.
Valentina GuarneriDepartment of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
C Kent OsborneDan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX.
Mothaffar F RimawiDan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX.
Baylor College of Medicine · USHospital Clínic de Barcelona · ESUniversity of North Carolina at Chapel Hill · USNovartis (Switzerland) · CHUniversity of Padua · ITVall d'Hebron Institute of Oncology · ESDana-Farber Cancer Institute · USHospital Arnau de Vilanova · ESHospital Clínico Universitario de Valencia · ESHospital Quirónsalud Barcelona · ESHospital Universitari Arnau de Vilanova · ESJohns Hopkins University · USMemorial Sloan Kettering Cancer Center · USUniversity of Alabama at Birmingham · USVall d'Hebron Hospital Universitari · ESVanderbilt University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Michael M Ittmann · 2007 to 2026
$73.9M
TUMOR SUPPRESSOR GENES IN BREAST CANCER DEVELOPMENTP50CA058183 · NCI · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI GUTIERREZ, CAROLLINA · 1992 to 2012
$30.9M
Translational Research in Breast Cancer (SPORE)P50CA186784 · NCI · BAYLOR COLLEGE OF MEDICINE · PI MATTHEW J ELLIS · 2014 to 2026
$24.5M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA125123NCI NIH HHS P50 CA058183NCI NIH HHS P50 CA186784
6 · The paper itself

Abstract

backgroundIdentification of HER2-positive breast cancers with high anti-HER2 sensitivity could help de-escalate chemotherapy. Here, we tested a clinically applicable RNA-based assay that combines ERBB2 and the HER2-enriched (HER2-E) intrinsic subtype in HER2-positive disease treated with dual HER2-blockade without chemotherapy.

methodsA research-based PAM50 assay was applied in 422 HER2-positive tumors from five II-III clinical trials (SOLTI-PAMELA, TBCRC023, TBCRC006, PER-ELISA, EGF104090). In SOLTI-PAMELA, TBCRC023, TBCRC006, and PER-ELISA, all patients had early disease and were treated with neoadjuvant lapatinib or pertuzumab plus trastuzumab for 12-24 weeks. Primary outcome was pathological complete response (pCR). In EGF104900, 296 women with advanced disease were randomized to receive either lapatinib alone or lapatinib plus trastuzumab. Progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) were evaluated.

resultsA total of 305 patients with early and 117 patients with advanced HER2-positive disease were analyzed. In early disease, HER2-E represented 83.8% and 44.7% of ERBB2-high and ERBB2-low tumors, respectively. Following lapatinib and trastuzumab, the HER2-E and ERBB2 (HER2-E/ERBB2)-high group showed a higher pCR rate compared to the rest (44.5%, 95% confidence interval [CI] = 35.4% to 53.9% vs 11.6%, 95% CI = 6.9% to 18.0%; adjusted odds ratio [OR] = 6.05, 95% CI = 3.10 to 11.80, P < .001). Similar findings were observed with neoadjuvant trastuzumab and pertuzumab (pCR rate of 66.7% in HER2-E/ERBB2-high, 95% CI = 22.3% to 95.7% vs 14.7% in others, 95% CI = 4.9% to 31.1%; adjusted OR = 11.60, 95% CI = 1.66 to 81.10, P = .01). In the advanced setting, the HER2-E/ERBB2-high group was independently associated with longer PFS (hazard ratio [HR] = 0.52, 95% CI = 0.35 to 0.79, P < .001); higher ORR (16.3%, 95% CI = 8.9% to 26.2% vs 3.7%, 95% CI = 0.8% to 10.3%, P = .02); and longer OS (HR = 0.66, 95% CI = 0.44 to 0.97, P = .01).

conclusionsCombining HER2-E subtype and ERBB2 mRNA into a single assay identifies tumors with high responsiveness to HER2-targeted therapy. This biomarker could help de-escalate chemotherapy in approximately 40% of patients with HER2-positive breast cancer.

Indexed as

Biomarkers, TumorGene ExpressionAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicErb-b2 Receptor Tyrosine KinasesFemaleHumansLapatinibMiddle AgedMolecular Targeted TherapyAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesLapatinibpertuzumab

Identifiers

PMID31037288
PMCPMC7850037
OpenAlexW2942862617

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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.