Abstract P2-08-22: The ASCO-recommended biomarkers urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 define a subgroup of patients with very low risk of recurrence under routine conditions
Authors: Thomssen C , Kantelhardt E-J , Grosse R , Papendick N , Steer S , Buchmann J , Wickenhauser C , Vetter M 
Published: May 2016

Background:

ASCO Tumor Marker Guidelines 2007 recommended clinical routine use of the invasion markers uPA and PAI-1 for risk assessment in node-negative breast cancer patients (Harris et al. JCO 2007; 25:5287), and in some countries, e.g. Germany and France, risk assessment using these markers is broadly used. We wanted to evaluate the impact of uPA/PAI-1 on identifying patients with low risk of recurrence also in the daily routine in order to demonstrate that &gt;25 years since their first description, these markers are still valuable.

Material and Methods:

We identified a cohort of 227 patients who were tested for uPA and PAI-1 in the clinical routine before 2012. Fresh frozen tissue of the primary tumor was obtained at biopsy or operation and processed for testing by a commercially available ELISA (FEMTELLE®, Sekisui Diagnostics GmbH) as previously described (Thomssen et al. JNCI 2009;101:1028). Tumor and patient characteristics were documented and all patients were regularly followed. Tumor concentrations below 3 ng/mg protein for uPA and below 14 ng/mg protein for PAI-1 were considered indicating low risk of recurrence (Harbeck et al. EJC 2013; 49:1825). Disease-free survival was defined as survival free from metastasis and loco-regional recurrence.

Results:

In our cohort, 86 patients had low tumor levels of uPA/PAI-1 (37.9 %). The median follow-up was 38.9 months (0.4 – 113.5 months). Adjuvant chemotherapy was delivered to 25 of 86 patients (29.1%) in the low risk group and to 85 of 141 patients (60.3%) in the high risk group; if steroid hormone receptor status was positive, generally adjuvant endocrine therapy for five years was advised. Using immunohistochemical subtyping, 73 of 86 patients with low uPA/PAI-1 values were luminal-like, 9 patients had a HER2-positive tumor and 3 patients had a triple negative breast cancer (TNBC). In patients with uPA or PAI-1 or both elevated, 105 of 141 patients had a luminal-like cancer, 12 patients were HER2 positive and 22 had TNBC; 1 case unknown. At 60 months of follow-up, patients with low uPA and/or PAI-1 tumor values had not experienced any recurrence, while in the high risk group 7 recurrences were observed although adequate adjuvant therapy was delivered (log-rank p=0.07). In node-negative pts with low uPA/PAI-1 values (n=72; pN0 70, cN0 2), no recurrences were observed, in 104 high risk patients 5 recurrences were observed (p=0.057).

Conclusions:

This observation confirms that also in daily routine, patients with a very low risk of recurrence can be identified by testing for uPA/PAI1. This group of pts comprises nearly 40% of pts and in these patients further evaluation with expensive predictive tests can be avoided and - above all - potentially toxic adjuvant chemotherapy can be spared.

Citation Format: Thomssen C, Kantelhardt E-J, Grosse R, Papendick N, Steer S, Buchmann J, Wickenhauser C, Vetter M. The ASCO-recommended biomarkers urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 define a subgroup of patients with very low risk of recurrence under routine conditions. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-22.