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High PDGFRb Express...
High PDGFRb Expression Predicts Resistance to Radiotherapy in DCIS within the SweDCIS Randomized Trial.
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- Strell, Carina (author)
- Uppsala universitet,Klinisk och experimentell patologi,Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.;Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
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- Folkvaljon, Dick (author)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.;Uppsala Univ, Dept Surg Sci, Uppsala, Sweden.
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- Holmberg, Erik, 1951 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology,Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Oncol,Inst Clin Sci, Gothenburg, Sweden.
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- Schiza, Aglaia (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab
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- Thurfjell, Viktoria (author)
- Uppsala universitet,Klinisk och experimentell patologi
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- Karlsson, Per, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology,Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Oncol,Inst Clin Sci, Gothenburg, Sweden.
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- Bergh, Jonas (author)
- Karolinska Institutet
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- Bremer, Troy (author)
- PreludeDx, Laguna Hills, CA USA.
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- Akslen, Lars A (author)
- Univ Bergen, Ctr Canc Biomarkers CCBIO, Dept Clin Med, Bergen, Norway.
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- Wärnberg, Fredrik (author)
- Uppsala universitet,Endokrinkirurgi,Uppsala Univ, Dept Surg Sci, Uppsala, Sweden.;Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Oncol,Inst Clin Sci, Gothenburg, Sweden.
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- Östman, Arne (author)
- Karolinska Institutet
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(creator_code:org_t)
- American Association For Cancer Research (AACR), 2021
- 2021
- English.
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In: Clinical cancer research : an official journal of the American Association for Cancer Research. - : American Association For Cancer Research (AACR). - 1557-3265 .- 1078-0432. ; 27:12, s. 3469-3477
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Abstract
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- This study analyzes the potential of stromal platelet-derived growth factor receptor-beta (PDGFRb) expression as biomarker for radiotherapy (RT) benefit on ipsilateral breast events (IBE) in ductal carcinoma in situ (DCIS). Improved identification of DCIS patients refractory to adjuvant whole-breast RT is needed. Predictive biomarker studies in DCIS have focused on tumor cell features rather than the tumor-associated stroma, despite growing evidence of its influence on therapy efficiency.Samples from the Swedish randomized radiotherapy DCIS trial (SweDCIS) were subjected to IHC analysis for stromal PDGFRb expression. IBE incidence at 10 years after breast-conserving surgery was the primary endpoint. Interactions between marker and treatment were analyzed.PDGFRb score was predictive for RT benefit with regard to IBE (Pinteraction = 0.002 and Pinteraction = 0.008 adjusted multivariably). Patients of the PDGFRblow group had a strong benefit from RT regarding IBE risk [HR, 0.23; 95% confidence interval (CI), 0.12-0.45; P < 0.001] with an absolute risk reduction of 21% (cumulative risk 7% vs. 28%) at 10 years. No significant risk reduction by RT was observed for patients of the PDGFRbhigh group (HR, 0.83; 0.51-1.34; P = 0.444; cumulative risk 22% vs. 25%). The RT response-predictive effect of stromal PDGFRb was equally strong in analyses for in situ and invasive IBE when analyzed separately (in situ IBE: P = 0.029; invasive IBE: P = 0.044).Results suggest high stromal PDGFRb expression as a novel biomarker identifying DCIS patients who are refractory to standard whole-breast adjuvant RT. The data imply previously unrecognized fibroblast-mediated modulation of radiosensitivity of DCIS, which should be further explored from mechanistic and targeting perspectives.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Strell, Carina
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Folkvaljon, Dick
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Holmberg, Erik, ...
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Schiza, Aglaia
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Thurfjell, Vikto ...
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Karlsson, Per, 1 ...
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Bergh, Jonas
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Bremer, Troy
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Akslen, Lars A
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Wärnberg, Fredri ...
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Östman, Arne
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Clinical cancer ...
- By the university
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University of Gothenburg
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Uppsala University
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Karolinska Institutet