ArticleBMC medicine2015
Constitutive phosphorylated STAT3-associated gene signature is predictive for trastuzumab resistance in primary HER2-positive breast cancer.
Article in BMC medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 58 citations in OpenAlex.
- Impact of Diabetes, Insulin, and Metformin Use on the Outcome of Patients With Human Epidermal Growth Factor Receptor 2-Positive Primary Breast Cancer: Analysis From the ALTTO Phase III Randomized Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2017 · on this mapTrial
- Article
- Leptin Drives Breast Cancer Aggressiveness Acting Through the Activation of the NCOA1/STAT3 Pathway.Medical sciences (Basel, Switzerland) · 2026Article
- Metabolic hallmarks of trastuzumab resistance.Expert opinion on therapeutic targets · 2025Review
- Advances in Molecular Diagnostics and Targeted Therapeutic Approaches in HER-2 Positive Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2025Review
- Induction of SUSD2 by STAT3 Activation Is Associated with Tumor Recurrence in HER2-Positive Breast Cancer.Cells · 2024Article
- The LDHC-STAT3 Signaling Network Is a Key Regulator of Basal-like Breast Cancer Cell Survival.Cancers · 2024Article
- Omics-based molecular classifications empowering in precision oncology.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent.Nature communications · 2023Article
- Stroma-derived miR-214 coordinates tumor dissemination.Journal of experimental & clinical cancer research : CR · 2023Article
- Review
- Inhibition of CDK8/19 Mediator kinase potentiates HER2-targeting drugs and bypasses resistance to these agents in vitro and in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- MUC1 is a potential target to overcome trastuzumab resistance in breast cancer therapy.Cancer cell international · 2022Review
- Article
- Trastuzumab resistance in HER2-positive breast cancer: Mechanisms, emerging biomarkers and targeting agents.Frontiers in oncology · 2022Review
- Resistance to endocrine therapy in HR + and/or HER2 + breast cancer: the most promising predictive biomarkers.Molecular biology reports · 2022Review
- Targeted Therapy Modulates the Secretome of Cancer-Associated Fibroblasts to Induce Resistance in HER2-Positive Breast Cancer.International journal of molecular sciences · 2021Article
- Meta-Analysis of Microdissected Breast Tumors Reveals Genes Regulated in the Stroma but Hidden in Bulk Analysis.Cancers · 2021Article
- Inference of phenotype-relevant transcriptional regulatory networks elucidates cancer type-specific regulatory mechanisms in a pan-cancer study.NPJ systems biology and applications · 2021Article
- Molecular Subtyping of Triple-Negative Breast Cancers by Immunohistochemistry: Molecular Basis and Clinical Relevance.The oncologist · 2020Article
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Authors and funding
19 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe likelihood of recurrence in patients with breast cancer who have HER2-positive tumors is relatively high, although trastuzumab is a remarkably effective drug in this setting. Signal transducer and activator of transcription 3 protein (STAT3), a transcription factor that is persistently tyrosine-705 phosphorylated (pSTAT3) in response to numerous oncogenic signaling pathways, activates downstream proliferative and anti-apoptotic pathways. We hypothesized that pSTAT3 expression in HER2-positive breast cancer will confer trastuzumab resistance.
methodsWe integrated reverse phase protein array (RPPA) and gene expression data from patients with HER2-positive breast cancer treated with trastuzumab in the adjuvant setting.
resultsWe show that a pSTAT3-associated gene signature (pSTAT3-GS) is able to predict pSTAT3 status in an independent dataset (TCGA; AUC = 0.77, P = 0.02). This suggests that STAT3 induces a characteristic set of gene expression changes in HER2-positive cancers. Tumors characterized as high pSTAT3-GS were associated with trastuzumab resistance (log rank P = 0.049). These results were confirmed using data from the prospective, randomized controlled FinHer study, where the effect was especially prominent in HER2-positive estrogen receptor (ER)-negative tumors (interaction test P = 0.02). Of interest, constitutively activated pSTAT3 tumors were associated with loss of PTEN, elevated IL6, and stromal reactivation.
conclusionsThis study provides compelling evidence for a link between pSTAT3 and trastuzumab resistance in HER2-positive primary breast cancers. Our results suggest that it may be valuable to add agents targeting the STAT3 pathway to trastuzumab for treatment of HER2-positive breast cancer.
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