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Low ERK Phosphorylation in Cancer-Associated Fibroblasts Is Associated with Tamoxifen Resistance in Pre-Menopausal Breast Cancer
University of Manchester, England .
University of Lund Hospital, Sweden .
Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
Lund University, Sweden .
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2012 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 7, no 9Article in journal (Refereed) Published
Abstract [en]

Purpose: The 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. less thanbrgreater than less thanbrgreater thanPatients and Methods: Tissue 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 (SMA alpha) in cancer-associated fibroblasts (CAFs) and links to clinico-pathological data and treatment-predictive values were delineated. less thanbrgreater than less thanbrgreater thanResults: By 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 (ER alpha-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 SMA alpha, a characteristic marker for activated fibroblasts. SMA alpha expression however was not linked to treatment-predictive information but instead had prognostic qualities. less thanbrgreater than less thanbrgreater thanConclusion: The 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.

Place, publisher, year, edition, pages
Public Library of Science , 2012. Vol. 7, no 9
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-85202DOI: 10.1371/journal.pone.0045669ISI: 000309554700056OAI: diva2:566640

Funding Agencies|Swedish Cancer Society and Breakthrough Breast Cancer UK||

Available from: 2012-11-09 Created: 2012-11-09 Last updated: 2012-11-28

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Stål, Olle
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OncologyFaculty of Health SciencesDepartment of Oncology UHL
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