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Introduction <p>An emerging challenge in early breast cancer (eBC) is improving risk assessment through the use of biomarkers. Clinical guidelines have recommended urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 for risk evaluation. This study aimed to validate the prognostic and predictive impact of uPA/PAI-1.</p> Patients and methods <p>From a prospective cohort of 1270 patients (PiA-study, Prognostic assessment in routine Application, NCT01592825), concentrations of uPA and PAI-1 were determined in fresh tumour tissue (<i>n</i> = 813) by ELISA (FEMTELLE®; LOXO Diagnostics). The uPA/PAI-1 status was defined as low if both uPA and PAI-1 levels were low and as high if one or both were elevated. Primary objectives were the distribution of the uPA/PAI-1 status and its association with clinical/histopathological parameters. Secondary objectives were the association of the uPA/PAI-1 status with recurrence-free interval (RFI), overall survival (OS), and benefit from adjuvant chemotherapy.</p> Results <p>A low uPA/PAI-1 status was observed in 37.6% (306 of 813) of the entire cohort and in 47.9% (181 of 378) of those classified as intermediate-risk patients (≥ 35yrs, ≤ pN1, G2, sHR positive/HER2 negative). A low uPA/PAI-1 status was associated with parameters that predict a favourable prognosis. Overall, 96.7% (95% CI 94.5–98.9) of patients with a low uPA/PAI-1-status remained recurrence-free at five years and 87.2% (95% CI 84.1–90.3) with a high uPA/PAI-1 status even after adjustment to tumour size, nodal status, grading, steroid&#xa0;hormone receptor&#xa0;(sHR) status and HER2 status (adjusted HR 2.6, 95% CI 1.29–5.23). Among intermediate-risk patients without chemotherapy (<i>n</i> = 197), the prognostic value was even more pronounced (HR 10.10, 95% CI 1.13–16.12). Similar results were observed for OS. Only patients with a high uPA/PAI-1 status appeared to benefit from chemotherapy (adjusted HR 0.28, 95% CI 0.07-1.12, <i>p</i> = 0.07).</p> Conclusion <p>This prospective analysis confirms the uPA/PAI-1 status as an independent prognostic factor and suggests a predictive impact considering benefit from chemotherapy.</p>

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Prospective validation of the prognostic and predictive impact of uPA/PAI-1 in early breast cancer

  • 期刊论文

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  • 发表日期：

    2025年12月8日

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  • Vanessa Wieder,
  • Julia Engel,
  • Kathleen Eichstädt,
  • Sandy Kaufhold,
  • Marcus Bauer,
  • Volker Hanf,
  • Christoph Uleer,
  • Susanne Peschel,
  • Jutta John,
  • Marleen Pöhler,
  • Tilmann Lantzsch,
  • Edith Weigert,
  • Karl-Friedrich Bürrig,
  • Jörg Buchmann,
  • Eva Johanna Kantelhardt,
  • Christoph Thomssen,
  • Martina Vetter

摘要

Introduction

An emerging challenge in early breast cancer (eBC) is improving risk assessment through the use of biomarkers. Clinical guidelines have recommended urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 for risk evaluation. This study aimed to validate the prognostic and predictive impact of uPA/PAI-1.

Patients and methods

From a prospective cohort of 1270 patients (PiA-study, Prognostic assessment in routine Application, NCT01592825), concentrations of uPA and PAI-1 were determined in fresh tumour tissue (n = 813) by ELISA (FEMTELLE®; LOXO Diagnostics). The uPA/PAI-1 status was defined as low if both uPA and PAI-1 levels were low and as high if one or both were elevated. Primary objectives were the distribution of the uPA/PAI-1 status and its association with clinical/histopathological parameters. Secondary objectives were the association of the uPA/PAI-1 status with recurrence-free interval (RFI), overall survival (OS), and benefit from adjuvant chemotherapy.

Results

A low uPA/PAI-1 status was observed in 37.6% (306 of 813) of the entire cohort and in 47.9% (181 of 378) of those classified as intermediate-risk patients (≥ 35yrs, ≤ pN1, G2, sHR positive/HER2 negative). A low uPA/PAI-1 status was associated with parameters that predict a favourable prognosis. Overall, 96.7% (95% CI 94.5–98.9) of patients with a low uPA/PAI-1-status remained recurrence-free at five years and 87.2% (95% CI 84.1–90.3) with a high uPA/PAI-1 status even after adjustment to tumour size, nodal status, grading, steroid hormone receptor (sHR) status and HER2 status (adjusted HR 2.6, 95% CI 1.29–5.23). Among intermediate-risk patients without chemotherapy (n = 197), the prognostic value was even more pronounced (HR 10.10, 95% CI 1.13–16.12). Similar results were observed for OS. Only patients with a high uPA/PAI-1 status appeared to benefit from chemotherapy (adjusted HR 0.28, 95% CI 0.07-1.12, p = 0.07).

Conclusion

This prospective analysis confirms the uPA/PAI-1 status as an independent prognostic factor and suggests a predictive impact considering benefit from chemotherapy.