Abstract P2-05-12: The ASCO-recommended prognostic factors uPA/PAI-1 in a multicenter cohort study (PiA)

Introduction The PiA-study (Prognostic assessment in routine Application, NCT 01592825) was designed as a representative cohort of breast cancer patients to estimate the proportions of traditional and modern prognostic factors. The ASCO-recommended biomarkers uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 were used for biological risk assessment particularly for intermediate risk breast cancer patients and disease-free survival of the patients after 5 yrs of follow-up (F/U) was calculated. Material & Methods Between 2009 and 2011, 1,074 non-metastasized, primarily operated breast cancer patients from six centers in Germany were included. From 815 patients, fresh frozen tissue was obtained and processed for central testing uPA/PAI-1 by ELISA (FEMTELLE®, Sekisui Diagnostics GmbH). Low uPA/PAI-1 status is defined by uPA and PAI-1 concentrations below the published cut-offs, high status means one or both were higher than the corresponding cut-offs. Tumor characteristics were based on local pathology. The centers had to follow the national guidelines. In low-risk patients, adjuvant chemotherapy was spared. The median F/U is 56 months (range 0-78). Results In the total cohort of 1,074 patients, 166 had G1- and 237 had G3-tumors. Of the 671 patients with a G2-tumor, the following were allocated to the high-risk group: node-positive (n=371), younger than 35 yrs (n=17), and triple-negative (TN) or HER2-positive (n=118). For 253 tumors of the remaining 355 patients with an intermediate risk of recurrence (pN0, G2, HR positive, HER2-negative, ≥35 yrs), uPA/PAI-1 status was available. 126 (49.8%) were allocated to the low-risk group, one patient had a recurrence. At 5 yrs, in the total cohort 90.6% (95% CI, 89.5-91.7) of the patients were free of invasive disease. Of 114 HER2-positive tumors, 94 (82.4 %) had a high uPA/PAI-1 status, only one of the 38 HR negative/HER2 positive tumors had a low uPA/PAI-1 status. In the TN group, the majority of tumors had a high uPA/PAI-1 status (66 of 81; 81.5 %). In 30 patients lymph nodes were involved, 18.5% (n=15) had a low uPA/PAI-1 status, one event was detected. In N pos. patients with an high uPA/PAI-1 6 events were observed. Conclusion Testing for uPA/PAI-1 in the daily routine is feasible, fresh frozen tissue has been prepared from 76% of the tumors of the recruited patients, 37% of them had a low risk status. Using uPA/PAI-1, about half of the node-negative patients with an intermediate risk of recurrence were allocated to a group with an extremely low risk of recurrence and thus chemotherapy could be spared. Also in node-positive disease, uPA/PAI-1 has a prognostic impact. Citation Format: Vetter M, Hartung C, Hanf V, Lantzsch T, Uleer C, Peschel S, John J, Buchmann J, Burrig K-F, Weigert E, Thomssen C, Kantelhardt EJ. The ASCO-recommended prognostic factors uPA/PAI-1 in a multicenter cohort study (PiA) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-12.