Prognostic and predictive impact of stroma cells defined by PDGFRb expression in early breast cancer: results from the randomized SweBCG91RT trial

Carina Strell, Axel Stenmark Tullberg, Reidunn Jetne Edelmann, Lars Andreas Akslen, Per Malmström, Mårten Fernö, Erik Holmberg, Arne Östman, Per Karlsson

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1 Citation (SciVal)

Abstract

Purpose: Predictive biomarkers are needed to aid the individualization of radiotherapy (RT) in breast cancer. Cancer-associated fibroblasts have been implicated in tumor radioresistance and can be identified by platelet-derived growth factor receptor-beta (PDGFRb). This study aims to analyze how PDGFRb expression affects RT benefit in a large randomized RT trial. Methods: PDGFRb was assessed by immunohistochemistry on tissue microarrays from 989 tumors of the SweBCG91RT trial, which enrolled lymph node-negative, stage I/IIA breast cancer patients randomized to RT after breast-conserving surgery. Outcomes were analyzed at 10 years for ipsilateral breast tumor recurrence (IBTR) and any recurrence and 15 years for breast cancer specific death (BCSD). Results: PDGFRb expression correlated with estrogen receptor negativity and younger age. An increased risk for any recurrence was noted in univariable analysis for the medium (HR 1.58, CI 95% 1.11–2.23, p = 0.011) or PDGFRb high group (1.49, 1.06–2.10, p = 0.021) compared to the low group. No differences in IBTR or BCSD risk were detected. RT benefit regarding IBTR risk was significant in the PDGFRb low (0.29, 0.12–0.67, p = 0.004) and medium (0.31, 0.16–0.59, p < 0.001) groups but not the PDGFRb high group (0.64, 0.36–1.11, p = 0.110) in multivariable analysis. Likewise, risk reduction for any recurrence was less pronounced in the PDGFRb high group. No significant interaction between RT and PDGFRb-score could be detected. Conclusion: A higher PDGFRb-score conferred an increased risk of any recurrence, which partly can be explained by its association with estrogen receptor negativity and young age. Reduced RT benefit was noted among patients with high PDGFRb, however without significant interaction.

Original languageEnglish
Pages (from-to)45-55
Number of pages11
JournalBreast Cancer Research and Treatment
Volume187
Issue number1
Early online date2021
DOIs
Publication statusPublished - 2021 May 1

Subject classification (UKÄ)

  • Cancer and Oncology

Keywords

  • Early breast cancer
  • Fibroblasts
  • PDGFR
  • Radiotherapy
  • Tumor microenvironment

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