Evidence map›Paper›PMID 21991949›Full record

Trial reportThe New England journal of medicine2011

Adjuvant trastuzumab in HER2-positive breast cancer.

Dennis Slamon, Wolfgang Eiermann, Nicholas Robert, Tadeusz Pienkowski, Miguel Martin, Michael Press, John Mackey, John Glaspy, Arlene Chan, Marek Pawlicki and 14 more

5 registry-linked trialsOpen access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in The New England journal of medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 5 registered trials, which are not on this map. Cited by 1,249 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,249citing papers in PubMed, 5 pooled it
78.3field-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.

NCT00021255 phase3completednot on this map

Multicenter Phase III Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed By Docetaxel (AC-T) With Doxorubicin and Cyclophosphamide Followed By Docetaxel and Trastuzumab (Herceptin)(AC-TH) and With Docetaxel, Carboplatin and Trastuzumab (TCH) In The Adjuvant Treatment Of Node Positive and High Risk Node Negative Patients With Operable Breast Cancer Containing The HER2 Alteration

TypeinterventionalSponsorSanofiRan2001 to 2014Enrolled3,222ConditionsBreast NeoplasmsArmsDoxorubicin, Cyclophosphamide, Docetaxel, Herceptin, Carboplatin
NCT02365831 unknown statusnot on this mapstarted 2015, after this paper: background citation

Evaluation of Medical Treatments in MBC HER2 Negative Patients in Italy - Observational Study

TypeobservationalSponsorConsorzio OncotechRan2015 to 2017Enrolled1,500ConditionsMetastatic Breast CancerArmsObservation of treatment management
NCT03429296 nacompletednot on this mapstarted 2018, after this paper: background citation

Prospective, Randomized Study Aiming to Assess the Benefit of Autohypnosis Learning in the Care of Patients Treated by Adjuvant Chemotherapy for Colorectal or Breast Cancer.

TypeinterventionalSponsorGroupe Hospitalier Mutualiste de GrenobleRan2018 to 2022Enrolled120ConditionsColorectal Cancer, Breast CancerArmsAutohypnosis learning
NCT03571633 phase2active not recruitingnot on this mapstarted 2018, after this paper: background citation

A Multicenter, Randomized, Open-label, Phase II Trial Aiming to Evaluate the Impact of Pegfilgrastim on Trastuzumab Anti-tumor Effect and ADCC in Operable HER2 Positive Breast Cancer Patients

TypeinterventionalSponsorCentre Leon BerardRan2018 to 2027Enrolled90ConditionsHER2-positive Breast Cancer, Operable Breast CancerArmsTrastuzumab + Paclitaxel, Pegfilgrastim
NCT07220135 phase2recruitingnot on this mapstarted 2025, after this paper: background citation

A Randomized Trial of Neoadjuvant THP vs TCHP for HER2-amplified/Positive Breast Cancer (NeoTHERa)

TypeinterventionalSponsorUniversity of Kansas Medical CenterRan2025 to 2031Enrolled100ConditionsBreast CancerArmsCarboplatin, Docetaxel, Trastuzumab (or biosimilar), Pertuzumab (or biosimilar)
3 · Its place in the literature

Who cites it

1,249 citing papers in PubMed, 5 syntheses or guidelines pooled it, 2,750 citations in OpenAlex.

  1. Guideline
  2. SEOM-GEICAM-SOLTI clinical guidelines for early-stage breast cancer (UPDATE 2025).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Guideline
  3. Pooled it
  4. Safety profile of trastuzumab originator vs biosimilars: a systematic review and meta-analysis of randomized clinical trials.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025
    Pooled it
  5. Guideline
  6. Trial
  7. Trial
  8. Trial
  9. Trial
  10. Trial
  11. Trial
  12. Trial
  13. Trial
  14. Trial
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Prognostic value of post-neoadjuvant pathological response and residual disease in early breast cancer: a real-world cohort study.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article

1,189 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 17 institutions in 12 countries.

Dennis SlamonJonsson Comprehensive Cancer Center, University of California–Los Angeles, Los Angeles, CA 90095-1678, USA. dslamon@mednet.ucla.edu
Wolfgang Eiermann
Nicholas Robert
Tadeusz Pienkowski
Miguel Martin
Michael Press
John Mackey
John Glaspy
Arlene Chan
Marek Pawlicki
Tamas Pinter
Vicente Valero
Mei-Ching Liu
Guido Sauter
Gunter von Minckwitz
Frances Visco
Valerie Bee
Marc Buyse
Belguendouz Bendahmane
Isabelle Tabah-Fisch
Mary-Ann Lindsay
Alessandro Riva
John Crown
Breast Cancer International Research Group
International Breast Cancer Study Group · CHSanofi (Mexico) · MXUniversity of Southern California · USBreast Cancer Alliance · USCancer Trials Ireland · IEHospital Clínico San Carlos · ESInternational Drug Development Institute (Belgium) · BEKlinik für Frauenheilkunde · DEKoo Foundation Sun Yat-Sen Cancer Center · TWKrankenhaus vom Roten Kreuz · DEMount Medical Centre · AUThe Maria Sklodowska-Curie National Research Institute of Oncology · PLThe University of Texas MD Anderson Cancer Center · USUCLA Jonsson Comprehensive Cancer CenterUniversität Hamburg · DEUniversity of Alberta · CAUniversity of California, Los Angeles · US

Funding

PATHOBIOLOGY OF BREAST CANCER AND HORMONE RECEPTORSR01CA048780 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI PRESS, MICHAEL F · 1988 to 2003
$1.1M
NCI NIH HHS CA 48780NCI NIH HHS R01 CA048780
6 · The paper itself

Abstract

backgroundTrastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity. We wanted to evaluate the efficacy and safety of a new nonanthracycline regimen with trastuzumab.

methodsWe randomly assigned 3222 women with HER2-positive early-stage breast cancer to receive doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T), the same regimen plus 52 weeks of trastuzumab (AC-T plus trastuzumab), or docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH). The primary study end point was disease-free survival. Secondary end points were overall survival and safety.

resultsAt a median follow-up of 65 months, 656 events triggered this protocol-specified analysis. The estimated disease-free survival rates at 5 years were 75% among patients receiving AC-T, 84% among those receiving AC-T plus trastuzumab, and 81% among those receiving TCH. Estimated rates of overall survival were 87%, 92%, and 91%, respectively. No significant differences in efficacy (disease-free or overall survival) were found between the two trastuzumab regimens, whereas both were superior to AC-T. The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group (P<0.001). Eight cases of acute leukemia were reported: seven in the groups receiving the anthracycline-based regimens and one in the TCH group subsequent to receiving an anthracycline outside the study.

conclusionsThe addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer. The risk-benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia. (Funded by Sanofi-Aventis and Genentech; BCIRG-006 ClinicalTrials.gov number, NCT00021255.).

Indexed as

Erb-b2 Receptor Tyrosine KinasesAnthracyclinesAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalFemaleHeart FailureHumansIntention to Treat AnalysisLeukemiaMiddle AgedStroke VolumeSurvival RateAnthracyclinesAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedErb-b2 Receptor Tyrosine KinasesTrastuzumab

Identifiers

PMID21991949
PMCPMC3268553
OpenAlexW2098775844

What OpenQuestion holds

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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.