ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Alpha-smooth Muscle Actin Expression in the Stroma Predicts Resistance to Trastuzumab in Patients with Early-stage HER2-positive Breast Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Postpartum breast cancer: evidence for a distinct phenotype.Journal of the National Cancer Institute · 2026Article
- Spatial proteomics for investigating solid tumor resistance mechanisms.Cancer metastasis reviews · 2025Review
- Tumor microenvironment response to neoadjuvant therapy in breast cancer: insights from single-cell and spatial omics.Medical oncology (Northwood, London, England) · 2025Review
- Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets.MedComm · 2025Review
- High α-SMA expression in the tumor stroma is associated with adverse clinical parameters in mismatch repair-proficient colorectal cancers only.American journal of clinical pathology · 2025Article
- Tumor and α-SMA-expressing stromal cells in pancreatic neuroendocrine tumors have a distinct RNA profile depending on tumor grade.Molecular oncology · 2025Article
- Cold and hot tumors: from molecular mechanisms to targeted therapy.Signal transduction and targeted therapy · 2024Review
- FGFR‑related phenotypic and functional profile of CAFs in prognostication of breast cancer (Review).International journal of oncology · 2024Review
- Rational Design of HER2-Targeted Combination Therapies to Reverse Drug Resistance in Fibroblast-Protected HER2+ Breast Cancer Cells.Cellular and molecular bioengineering · 2024Article
- Spatial proteomics: unveiling the multidimensional landscape of protein localization in human diseases.Proteome science · 2024Review
- Depicting Biomarkers for HER2-Inhibitor Resistance: Implication for Therapy in HER2-Positive Breast Cancer.Cancers · 2024Review
- Cancer-associated fibroblasts (CAFs) gene signatures predict outcomes in breast and prostate tumor patients.Journal of translational medicine · 2024Article
- The obese inflammatory microenvironment may promote breast DCIS progression.Frontiers in immunology · 2024Article
- Delving into the Role of α-Smooth Muscle Actin as a Predictive Biomarker of Early Recurrence in Invasive Ductal Adenocarcinoma of Breast.Iranian journal of pathology · 2024Article
- Radiogenomic analysis of cellular tumor-stroma heterogeneity as a prognostic predictor in breast cancer.Journal of translational medicine · 2023Article
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- Intertumoral Differences Dictate the Outcome of TGF-β Blockade on the Efficacy of Viro-Immunotherapy.Cancer research communications · 2023Article
- Cancer-educated mammary adipose tissue-derived stromal/stem cells in obesity and breast cancer: spatial regulation and function.Journal of experimental & clinical cancer research : CR · 2023Article
- Assessment of Cognitive Function with Sleep Spindle Characteristics in Adults with Epilepsy.Neural plasticity · 2023Article
Corrections and comments
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Authors and funding
23 authors at 13 institutions in 10 countries.
Funding
Abstract
purposeThe companion diagnostic test for trastuzumab has not changed much in the last 25 years. We used high-plex digital spatial profiling to identify biomarkers besides HER2 that can help predict response to trastuzumab in HER2-positive breast cancer. EXPERIMENTAL
designFifty-eight protein targets were measured in three different molecularly defined compartments by the NanoString GeoMx Digital Spatial Profiler (DSP) in a tissue microarray containing 151 patients with breast cancer that received adjuvant trastuzumab as part of the Hellenic Cooperative Oncology Group 10/05 clinical trial. Promising candidate biomarkers were orthogonally validated with quantitative immunofluorescence (QIF). RNA-sequencing data from the Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation Study (NeoALTTO) were accessed to provide independent cohort validation. Disease-free survival (DFS) was the main outcome assessed. Statistical analyses were performed using a two-sided test (α = 0.05) and multiple testing correction (Benjamini-Hochberg method, FDR < 0.1).
resultsBy DSP, high expression of alpha-smooth muscle actin (α-SMA), both in the leukocyte and stromal compartments, was associated with shorter DFS in univariate analysis (
conclusionsThis work identifies α-SMA as a novel, easy-to-implement biomarker of resistance to trastuzumab that may be valuable in settings where trastuzumab is combined with other therapies.
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