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• W3087407560 abstract "Experimental studies suggest that hepatocyte growth factor (HGF) and its transmembrane tyrosine kinase receptor, Met, in part also relying on Akt kinase activity, mediate radioresistance. We investigated the importance of these biomarkers for the risk of ipsilateral breast tumour recurrence (IBTR) after adjuvant radiotherapy (RT) in primary breast cancer. HGF, phosphorylated Met (pMet) and phosphorylated Akt (pAkt) were evaluated immunohistochemically on tissue microarrays from 1004 patients in the SweBCG91‐RT trial, which randomly assigned patients to breast‐conserving therapy, with or without adjuvant RT. HGF was evaluated in the stroma (HGF str ); pMet in the membrane (pMet mem ); HGF, pMet and pAkt in the cytoplasm (HGF cyt , pMet cyt , pAkt cyt ); and pAkt in the nucleus (pAkt nuc ). The prognostic and treatment predictive effects were evaluated to primary endpoint IBTR as first event during the first 5 years. Patients with tumours expressing low levels of HGF cyt and pMet cyt and high levels of pAkt nuc derived a larger benefit from RT [hazard ratio (HR): 0.11 (0.037–0.30), 0.066 (0.016–0.28) and 0.094 (0.028–0.31), respectively] compared to patients with high expression of HGF cyt and pMet cyt , and low pAkt nuc [HR: 0.36 (0.19–0.67), 0.35 (0.20–0.64) and 0.47 (0.32–0.71), respectively; interaction analyses: P = 0.052, 0.035 and 0.013, respectively]. These differences remained in multivariable analysis when adjusting for patient age, tumour size, histological grade, St Gallen subtype and systemic treatment (interaction analysis, P ‐values: 0.085, 0.027, and 0.023, respectively). This study suggests that patients with immunohistochemically low HGF cyt , low pMet cyt and high pAkt nuc may derive an increased benefit from RT after breast‐conserving surgery concerning the risk of developing IBTR." @default.
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• W3087407560 date "2020-09-28" @default.
• W3087407560 modified "2023-10-16" @default.
• W3087407560 title "Expression of HGF, pMet, and pAkt is related to benefit of radiotherapy after breast‐conserving surgery: a long‐term follow‐up of the SweBCG91‐RT randomised trial" @default.
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• W3087407560 doi "https://doi.org/10.1002/1878-0261.12803" @default.
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