Evidence map›Paper›PMID 29898752›Full record

Trial reportBreast cancer research : BCR2018

Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer.

Nadine Norton, Nicholas Fox, Christie-Ann McCarl, Kathleen S Tenner, Karla Ballman, Courtney L Erskine, Brian M Necela, Donald Northfelt, Winston W Tan, Carmen Calfa and 5 more

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Breast cancer research : BCR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00005970 (Phase III Trial of Doxorubicin and Cyclophosphamide), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 21% 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.

NCT00005970 phase3completednot on this map

Phase III Trial of Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Paclitaxel With or Without Trastuzumab as Adjuvant Treatment for Women With HER-2 Over-Expressing or Amplified Node Positive or High-Risk Node Negative Breast Cancer

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2000 to 2010Enrolled3,436ConditionsBreast Adenocarcinoma, HER2 Positive Breast Carcinoma, Stage IA Breast Cancer AJCC v7, Stage IB Breast Cancer AJCC v7ArmsAromatase Inhibition Therapy, Cyclophosphamide, Doxorubicin Hydrochloride, Laboratory Biomarker Analysis, Paclitaxel
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 15 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Role of Fcγ receptors in HER2-targeted breast cancer therapy.Journal for immunotherapy of cancer · 2022
    Review
  5. Review
  6. Rapid Generation of Sustainable HER2-specific T-cell Immunity in Patients with HER2 Breast Cancer using a Degenerate HLA Class II Epitope Vaccine.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Article
  7. Article
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

15 authors at 7 institutions in 1 country.

Nadine NortonDepartment of Cancer Biology, Mayo Clinic, Jacksonville, FL, 32224, USA.
Nicholas FoxDepartment of Pathology, Medicine and Dermatology, Columbia University Medical Center, New York, NY, 10032, USA.
Christie-Ann McCarlDepartment of Pathology, Medicine and Dermatology, Columbia University Medical Center, New York, NY, 10032, USA.
Kathleen S TennerDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN, 55905, USA.
Karla BallmanDepartment of Healthcare Policy and Research, Weill Cornell Medicine, New York, NY, USA.
Courtney L ErskineDepartment of Immunology, Mayo Clinic, Rochester, MN, 55905, USA.
Brian M NecelaDepartment of Cancer Biology, Mayo Clinic, Jacksonville, FL, 32224, USA.
Donald NorthfeltDepartment of Hematology and Oncology, Mayo Clinic, Scottsdale, AZ, 85259, USA.
Winston W TanDepartment of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, 32224, USA.
Carmen CalfaSylvester Cancer Center, University of Miami, Miami, FL, 33136, USA.
Mark PegramDepartment of Medicine, Stanford University, Stanford, CA, 94305, USA.
Gerardo Colon-OteroDepartment of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, 32224, USA.
Edith A PerezDepartment of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, 32224, USA. perez.edith@mayo.edu.
Raphael ClynesDepartment of Pathology, Medicine and Dermatology, Columbia University Medical Center, New York, NY, 10032, USA. rclynes@xencor.com.
Keith L KnutsonDepartment of Immunology, Mayo Clinic, Jacksonville, FL, 32224, USA. knutson.keith@mayo.edu.
Mayo Clinic in Florida · USColumbia University Irving Medical Center · USCornell University · USMayo Clinic in Arizona · USStanford University · USSylvester Comprehensive Cancer Center · USWinnMed · US

Funding

Role of Immunity in Efficacy of Chemotherapy Plus TrastuzumabR01CA152045 · NCI · MAYO CLINIC JACKSONVILLE · PI KNUTSON, KEITH L., PEREZ, EDITH A. · 2011 to 2015
$2.7M
NCI NIH HHS R01 CA152045
6 · The paper itself

Abstract

backgroundResected HER2 breast cancer patients treated with adjuvant trastuzumab and chemotherapy have superior survival compared to patients treated with chemotherapy alone. We previously showed that trastuzumab and chemotherapy induce HER2-specific antibodies which correlate with improved survival in HER2 metastatic breast cancer patients. It remains unclear whether the generation of immunity required trastuzumab and whether endogenous antibody immunity is associated with improved disease-free survival in the adjuvant setting. In this study, we addressed this question by analyzing serum anti-HER2 antibodies from a subset of patients enrolled in the NCCTG trial N9831, which includes an arm (Arm A) in which trastuzumab was not used. Arms B and C received trastuzumab sequentially or concurrently to chemotherapy, respectively.

methodsPre-and post-treatment initiation sera were obtained from 50 women enrolled in N9831. Lambda IgG antibodies (to avoid detection of trastuzumab) to HER2 were measured and compared between arms and with disease-free survival.

resultsPrior to therapy, across all three arms, N9831 patients had similar mean anti-HER2 IgG levels. Following treatment, the mean levels of antibodies increased in the trastuzumab arms but not the chemotherapy-only arm. The proportion of patients who demonstrated antibodies increased by 4% in Arm A and by 43% in the Arms B and C combined (p = 0.003). Cox modeling demonstrated that larger increases in antibodies were associated with improved disease-free survival in all patients (HR = 0.23; p = 0.04).

conclusionsThese results show that the increased endogenous antibody immunity observed in adjuvant patients treated with combination trastuzumab and chemotherapy is clinically significant, in view of its correlation with improved disease-free survival. The findings may have important implications for predicting treatment outcomes in patients treated with trastuzumab in the adjuvant setting.

trial registrationClinicalTrials.gov, NCT00005970 . Registered on July 5, 2000.

Indexed as

AdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantCombined Modality TherapyDisease-Free SurvivalErb-b2 Receptor Tyrosine KinasesFemaleHumansKaplan-Meier EstimateMiddle AgedNeoplasm MetastasisNeoplasm Recurrence, LocalAntibodies, Monoclonal, HumanizedBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesTrastuzumabAdaptive immune responseDisease-free survivalHER2 +Trastuzumab

Identifiers

PMID29898752
PMCPMC6000975
OpenAlexW2808624400

What OpenQuestion holds

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LicenceCC BY
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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.