title: High expression of stromal PDGFRβ is associated with reduced benefit of tamoxifen in breast cancer.
abstract: Cancer-associated fibroblasts (CAFs) regulate tumour growth, metastasis and response to treatment. Recent studies indicate the existence of functionally distinct CAF subsets. Suggested mechanisms whereby CAFs can impact on treatment response include paracrine signalling affecting cancer cell drug sensitivity and effects on tumour drug uptake. PDGFRβ is an important regulator of fibroblasts. Experimental studies have linked PDGFRβ-positive fibroblasts to metastasis and also to reduced tumour drug uptake. This study has investigated the potential role of PDGFRβ-positive fibroblasts in response to adjuvant tamoxifen treatment of breast cancer. Analyses of two breast cancer collections from randomised studies analysing adjuvant tamoxifen treatment in early breast cancer demonstrated significant benefit of tamoxifen in the group with low stromal PDGFRβ, which was not observed in the group with high stromal PDGFRβ. In general terms these findings provide novel evidence, derived from analyses of randomised clinical studies, of response-predictive capacity of a marker-defined subset of CAFs and, more specifically, identify stromal PDGFRβ as a marker related to tamoxifen benefit in early breast cancer.
authors.affiliation: Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm Sweden.
authors.forename: Janna
authors.initials: J
authors.lastname: Paulsson
authors.affiliation: Division of Surgery, Department of Clinical SciencesLund UniversityLundSweden; Department of SurgerySkåne University HospitalLundSweden.
authors.forename: Lisa
authors.initials: L
authors.lastname: Rydén
authors.affiliation: Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Strell
authors.affiliation: Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm Sweden.
authors.forename: Oliver
authors.initials: O
authors.lastname: Frings
authors.affiliation: Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm Sweden.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Tobin
authors.affiliation: Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm Sweden.
authors.forename: Tommy
authors.initials: T
authors.lastname: Fornander
authors.affiliation: Department of Oncology-PathologyCancer Center Karolinska, Karolinska InstitutetStockholmSweden; Radiumhemmet, Karolinska University HospitalStockholmSweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.affiliation: Department of Pathology Sahlgrenska Cancer Centre, University of Gothenburg Gothenburg Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Landberg
authors.affiliation: Department of Clinical and Experimental Medicine Oncology, Linköping University Linköping Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Stål
authors.affiliation: Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm Sweden.
authors.forename: Arne
authors.initials: A
authors.lastname: Östman
keywords: PDGFRβ; breast cancer; tamoxifen; tumour stroma