Data from High PDGFRb Expression Predicts Resistance to Radiotherapy in DCIS within the SweDCIS Randomized Trial

Abstract

<div>AbstractPurpose:<p>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 <i>in situ</i> (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.</p>Experimental Design:<p>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.</p>Results:<p>PDGFRb score was predictive for RT benefit with regard to IBE (<i>P</i><sub>interaction</sub> = 0.002 and <i>P</i><sub>interaction</sub> = 0.008 adjusted multivariably). Patients of the PDGFRb<sup>low</sup> group had a strong benefit from RT regarding IBE risk [HR, 0.23; 95% confidence interval (CI), 0.12–0.45; <i>P</i> < 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 PDGFRb<sup>high</sup> group (HR, 0.83; 0.51–1.34; <i>P</i> = 0.444; cumulative risk 22% vs. 25%). The RT response–predictive effect of stromal PDGFRb was equally strong in analyses for <i>in situ</i> and invasive IBE when analyzed separately (<i>in situ</i> IBE: <i>P</i> = 0.029; invasive IBE: <i>P</i> = 0.044).</p>Conclusions:<p>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.</p></div>