Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2015
Genomic analysis reveals that immune function genes are strongly linked to clinical outcome in the North Central Cancer Treatment Group n9831 Adjuvant Trastuzumab Trial.
Abstract readRandomized Controlled TrialValidation Study
In one paragraph
Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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112citing papers in PubMed
–field-weighted citation impact
What it found
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The trial behind it
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Who cites it
112 citing papers in PubMed.
- Computationally Derived Spatial Immune Signature Identifies Trastuzumab Responders in HER2+ Breast Cancer: NSABP B-41 Clinical Trial Validation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Impact of RNA Signatures on pCR and Survival after 12-Week Neoadjuvant Pertuzumab plus Trastuzumab with or without Paclitaxel in the WSG-ADAPT HER2+/HR- Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- Tumor biomarkers and efficacy in patients treated with trastuzumab emtansine + pertuzumab versus standard of care in HER2-positive early breast cancer: an open-label, phase III study (KRISTINE).Breast cancer research : BCR · 2023Trial
- Beta-2 Adrenergic Receptor Gene Expression in HER2-Positive Early-Stage Breast Cancer Patients: A Post-hoc Analysis of the NCCTG-N9831 (Alliance) Trial.Clinical breast cancer · 2022Trial
- Genomic signatures define three subtypes of EGFR-mutant stage II-III non-small-cell lung cancer with distinct adjuvant therapy outcomes.Nature communications · 2021Trial
- Pathologic and molecular responses to neoadjuvant trastuzumab and/or lapatinib from a phase II randomized trial in HER2-positive breast cancer (TRIO-US B07).Nature communications · 2020Trial
- Evaluation of the Predictive Role of Tumor Immune Infiltrate in Patients with HER2-Positive Breast Cancer Treated with Neoadjuvant Anti-HER2 Therapy without Chemotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- Transcriptomic profiles conducive to immune-mediated tumor rejection in human breast cancer skin metastases treated with Imiquimod.Scientific reports · 2019Trial
- Tumor-Infiltrating Lymphocytes in Patients Receiving Trastuzumab/Pertuzumab-Based Chemotherapy: A TRYPHAENA Substudy.Journal of the National Cancer Institute · 2019Trial
- Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer.Breast cancer research : BCR · 2018Trial
- Robust estimation of the expected survival probabilities from high-dimensional Cox models with biomarker-by-treatment interactions in randomized clinical trials.BMC medical research methodology · 2017Trial
- Pathway level alterations rather than mutations in single genes predict response to HER2-targeted therapies in the neo-ALTTO trial.Annals of oncology : official journal of the European Society for Medical Oncology · 2017Trial
- A phase II study of clinical activity of SCH 717454 (robatumumab) in patients with relapsed osteosarcoma and Ewing sarcoma.Pediatric blood & cancer · 2016Trial
- Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to PreoperativeTrastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016Trial
- Association of Stromal Tumor-Infiltrating Lymphocytes With Recurrence-Free Survival in the N9831 Adjuvant Trial in Patients With Early-Stage HER2-Positive Breast Cancer.JAMA oncology · 2016Trial
- Identification of Gene Regulatory Networks Associated with Breast Cancer Patient Survival Using an Interpretable Deep Neural Network Model.Expert systems with applications · 2025Article
- Histamine N-methyltransferase (HNMT) as a potential auxiliary biomarker for predicting adaptability to anti-HER2 drug treatment in breast cancer patients.Biomarker research · 2025Article
- Biparatopic HER2-targeted nanobody binder synergizes with trastuzumab in resistant tumor cells.Frontiers in immunology · 2025Article
- DLL4-targeted CAR-T therapy sensitizes neoadjuvant chemotherapy via eliminating cancer stem cells and reshaping immune microenvironment in HER2Journal for immunotherapy of cancer · 2024Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors.
Edith A PerezEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA. perez.edith@mayo.edu.
E Aubrey ThompsonEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Karla V BallmanEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
S Keith AndersonEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Yan W AsmannEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Krishna R KalariEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Jeanette E Eckel-PassowEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Amylou C DueckEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Kathleen S TennerEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Jin JenEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Jian-Bing FanEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Xochiquetzal J GeigerEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Ann E McCulloughEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Beiyun ChenEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Robert B JenkinsEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
George W SledgeEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Eric P WinerEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Julie R GralowEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Monica M ReinholzEdith A. Perez, E. Aubrey Thompson, Yan W. Asmann, and Xochiquetzal J. Geiger, Mayo Clinic, Jacksonville, FL; Karla V. Ballman, S. Keith Anderson, Krishna R. Kalari, Jeanette E. Eckel-Passow, Kathleen S. Tenner, Jin Jen, Beiyun Chen, Robert B. Jenkins, and Monica M. Reinholz, Mayo Clinic, Rochester, MN; Amylou C. Dueck, and Ann E. McCullough, Mayo Clinic, Scottsdale, AZ; Jian-Bing Fan, Illumina, San Diego, CA; George W. Sledge, Stanford School of Medicine, Palo Alto, CA; Eric P. Winer, Harvard Medical School, Boston, MA; and Julie R. Gralow, Seattle Cancer Care Alliance, Seattle, WA.
Funding
Member Site CoreU10CA180821 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI Evanthia Galanis, Olwen Hahn · 2014 to 2026
$177.3MSWOG Network Group Operations Center of the NCTNU10CA180888 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI PRIMO N. LARA · 2014 to 2026
$152.1MWomen's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3MTHE ALLIANCE NCTN BIOREPOSITORY AND BIOSPECIMEN RESOURCEU24CA196171 · NCI · WASHINGTON UNIVERSITY · PI Mine Cicek, Wendy Frankel · 2015 to 2026
$35.0MNorth Central Cancer Treatment Group (NCCTG) Biospecimen ResourceU24CA114740 · NCI · MAYO CLINIC ROCHESTER · PI BUCKNER, JAN C · 2005 to 2014
$8.6MPredictive Biomarkers of Adjuvant Trastuzumab in the HER2+N9831 Intergroup TrialR01CA129949 · NCI · MAYO CLINIC JACKSONVILLE · PI PEREZ, EDITH A. · 2008 to 2011
$1.3MNCI NIH HHS CA114740NCI NIH HHS CA129949NCI NIH HHS CA25225NCI NIH HHS N01 CA015083NCI NIH HHS P30 CA015083NCI NIH HHS R01 CA129949NCI NIH HHS U10 CA180821NCI NIH HHS U10 CA180888NCI NIH HHS U24 CA114740NCI NIH HHS U24 CA196171
Abstract
purposeTo develop a genomic signature that predicts benefit from trastuzumab in human epidermal growth factor receptor 2-positive breast cancer. PATIENTS AND
methodsDASL technology was used to quantify mRNA in samples from 1,282 patients enrolled onto the Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer (North Central Cancer Treatment Group N9831 [NCCTG-N9831]) adjuvant trastuzumab trial. Cox proportional hazard ratios (HRs), adjusted for significant clinicopathologic risk factors, were used to determine the association of each gene with relapse-free survival (RFS) for 433 patients who received chemotherapy alone (arm A) and 849 patients who received chemotherapy plus trastuzumab (arms B and C). Network and pathway analyses were used to identify key biologic processes linked to RFS. The signature was built by using a voting scheme.
resultsNetwork and functional ontology analyses suggested that increased RFS was linked to a subset of immune function genes. A voting scheme model was used to define immune gene enrichment based on the expression of any nine or more of 14 immune function genes at or above the 0.40 quantile for the population. This model was used to identify immune gene-enriched tumors in arm A and arms B and C. Immune gene enrichment was linked to increased RFS in arms B and C (HR, 0.35; 95% CI, 0.22 to 0.55; P < .001), whereas arm B and C patients who did not exhibit immune gene enrichment did not benefit from trastuzumab (HR, 0.89; 95% CI, 0.62 to 1.28; P = .53). Enriched immune function gene expression as defined by our predictive signature was not associated with increased RFS in arm A (HR, 0.90; 95% CI, 0.60 to 1.37; P = .64).
conclusionIncreased expression of a subset of immune function genes may provide a means of predicting benefit from adjuvant trastuzumab.
Indexed as
Molecular Targeted TherapyAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalDNA, NeoplasmErb-b2 Receptor Tyrosine KinasesFemaleGene Expression Regulation, NeoplasticGenomicsHumansKaplan-Meier EstimateAntibodies, Monoclonal, HumanizedBiomarkers, TumorDNA, NeoplasmERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesTrastuzumab
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