ArticlePloS one2012
Low ERK phosphorylation in cancer-associated fibroblasts is associated with tamoxifen resistance in pre-menopausal breast cancer.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Pooled it
- Trial
- Review
- FGFR‑related phenotypic and functional profile of CAFs in prognostication of breast cancer (Review).International journal of oncology · 2024Review
- Review
- FGFs/FGFRs-dependent signalling in regulation of steroid hormone receptors - implications for therapy of luminal breast cancer.Journal of experimental & clinical cancer research : CR · 2019Review
- High expression of stromal PDGFRβ is associated with reduced benefit of tamoxifen in breast cancer.The journal of pathology. Clinical research · 2017Article
- Clinicopathological and prognostic significance of mitogen-activated protein kinases (MAPK) in breast cancers.Breast cancer research and treatment · 2016Article
- Letrozole-induced functional changes in carcinoma-associated fibroblasts and their influence on breast cancer cell biology.Medical oncology (Northwood, London, England) · 2016Article
- Liquid-based three-dimensional tumor models for cancer research and drug discovery.Experimental biology and medicine (Maywood, N.J.) · 2016Review
- Tumour cell-derived Wnt7a recruits and activates fibroblasts to promote tumour aggressiveness.Nature communications · 2016Article
- CAF-specific markers: role of the TGFβ pathway.Oncoscience · 2015Article
- PSEA: Kinase-specific prediction and analysis of human phosphorylation substrates.Scientific reports · 2014Article
- Genistein attenuates brain damage induced by transient cerebral ischemia through up-regulation of ERK activity in ovariectomized mice.International journal of biological sciences · 2014Article
- An approach to evaluating and comparing biomarkers for patient treatment selection.The international journal of biostatistics · 2014Article
Corrections and comments
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Authors and funding
5 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe aim of this study was to evaluate ERK phosphorylation as a stromal biomarker for breast cancer prognosis and tamoxifen treatment prediction within a randomized tamoxifen trial. PATIENTS AND
methodsTissue microarrays of two breast cancer cohorts including in total 743 invasive breast cancer samples were analyzed for ERK phosphorylation (pERK) and smooth muscle actin-alpha expression (SMAα) in cancer-associated fibroblasts (CAFs) and links to clinico-pathological data and treatment-predictive values were delineated.
resultsBy analyzing a unique randomized tamoxifen trial including breast cancer patients receiving no adjuvant treatment we show for the first time that patients low in ERK phosphorylation in CAFs did not respond to tamoxifen treatment despite having estrogen-receptor alpha (ERα-positive tumors compared to patients with high pERK levels in CAFs (P = 0.015, multivariate Cox regression interaction analysis). In both clinical materials we further show a significant association between pERK and SMAα, a characteristic marker for activated fibroblasts. SMAα expression however was not linked to treatment-predictive information but instead had prognostic qualities.
conclusionThe data suggests that the presence of a subpopulation of CAFs, defined by minimal activated ERK signaling, is linked to an impaired tamoxifen response. Thus, this report illustrates the importance of the stroma for monitoring treatment effects in pre-menopausal breast cancer.
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