Comparison of Prosigna® Assay and Urokinase Plasminogen Activator/Plasminogen Activator Inhibitor-1 Results in...

The decision-making process regarding adjuvant treatment in estrogen receptor-positive (ER+), HER2-negative early-stage breast cancer (EBC) is often not sufficient, when based on established clinicopathological parameters. Additional prognostic tests could facilitate these decisions. This paper compares the well-validated invasion marker urokinase plasminogen activator/plasminogen activator inhibitor-1 (uPA/PAI-1) with the Prosigna® assay, which is based on the PAM50 gene signature. Prosigna® also provides a prognostic risk assessment (risk of recurrence, Prosigna®-ROR), taking tumor burden and the intrinsic molecular subtype into account.

From October 2013 to April 2014, we selected 42 postmenopausal EBC patients (ER+/HER2-) from the database of the Breast Centre of the University of Munich (LMU). In the context of therapy decision-making, uPA/PAI-1 testing had already been performed on the selected patients' fresh frozen tumor tissue. The patient's data were pseudonymized, and the Prosigna® assay was performed retrospectively using archived Formalin-fixed paraffin-embedded tumor samples. A 5-year follow-up was carried out in March 2021.

All patients (n = 42) had ER+/HER2-negative invasive breast cancers. According to Prosigna®, 22 (52.4%) tumors were classified as low-risk, 14 (33.3%) as intermediate-risk, and 6 (14.3%) as high-risk. Among the 22 Prosigna® low-risk tumors, 13 (59.1%) were classified as uPA/PAI-1 low-risk and 9 (40.9%) were classified as uPA/PAI-1 high-risk. The 14 Prosigna® intermediate-risk tumors divided into 6 (42.9%) uPA/PAI-1 low-risk and 8 (57.1%) uPA/PAI-1 high-risk. Among the 6 patients classified as high-risk using Prosigna®-ROR, one (16.7%) was classified as low-risk and the other 5 (83.3%) as high-risk using uPA/PAI-1. The comparison of the intrinsic subtypes (luminal A, luminal B, basal-like) based on Prosigna® assay with the risk groups of uPA/PAI-1 showed only poor correlation. A 5-year follow-up with the endpoints ipsilateral recurrence, contralateral recurrence, distant metastasis, and death could be obtained in 67% (28/42) of the initially included patients. In two of these cases, one of these events occurred. The risk stratification of uPA/PAI-1 and Prosigna® did not match in these tumors.

In luminal EBC, there is only limited concordance between risk group classification according to the Prosigna®-ROR, Prosigna®-luminal subtypes, and risk classification by uPA/PAI-1. Risk classification by uPA/PAI-1 compared to the Prosigna® assay resulted in a larger high-risk group with a clear recommendation for adjuvant chemotherapy (CTX). A larger study population in a prospective setting and more detailed outcome data would be necessary to understand the clinical relevance of the observed discrepancies. Only one evidence-based guideline-recommended prognostic test should be used in a single patient for CTX decision-making.