284P - Prognostic and predictive impact of uPA/PAI-1 in early breast cancer

Background

The prognostic marker uPA/PAI-1 is recommended by international guidelines for treatment decisions in node-negative breast cancer (BC). This study is aimed at validating the prognostic impact of uPA/PAI-1 by using a daily routine cohort and to consider the predictive impact with regard to chemotherapy in HR+ /HER2- breast cancer.

Methods

In a multicentre cohort study (PiA-study, Prognostic assessment in routine Application n=1,270, NCT 01592825), the concentrations of uPA and PAI-1 in fresh tumour tissue (n=813) were prospectively determined by ELISA (FEMTELLE®, BioMedica Diagnostics GmbH). The first objective was the association of uPA/PAI-1 with recurrence-free Interval (5 yrs RFI) and overall survival (5 yrs OS). As the second objective, we evaluated the impact of uPA/PAI-1 as a predictive factor for adjuvant chemotherapy in the intermediate risk group, which was defined as HR+, HER2-, G2, ≥35 yrs., 0-3 positive lymph nodes. Median follow-up was 60.3 months (1-129).

Results

After 5 years of observation, 96.7% (95% CI 94.5-98.9) of patients with low uPA/PAI-1 were without any RFI event compared to 87.2% (95% CI 84.1-90.3) with high uPA/PAI-1 (aHR 2.6, 95% CI 1.293-5.227, p=0.001). Also considering OS, a significant difference was detected; with low uPA/PAI-1, 93.9% (95% CI 91.0-96.8) were alive after 5 years (aHR 2.38, 95% CI 1.359-4.156) compared to 82.9% (95% CI 79.1-86.4) with high uPA/PAI-1. With regard to the intermediate risk group (n=378), even without chemotherapy, less than 1% of patients with low uPA/PAI-1 (n=120) had an RFI event. While patients with high uPA/PAI-1 had a significantly higher risk of disease-related events over the entire observation time (aHR 4.27, 95% CI 1.132-16.124). If patients were treated with adjuvant chemotherapy (n=181), uPA/PAI-1 had no further prognostic significance. Patients with high uPA/PAI-1 benefited significantly from adjuvant chemotherapy compared to patients without chemotherapy (aHR 0.21, 95% CI 0.076-0.600).

Conclusions

These real-world cohort data confirm that uPA/PAI-1 can routinely be used as an independent prognostic factor for decisions about adjuvant chemotherapy and underline the assumption that uPA/PAI-1 might be predictive for the effect of adjuvant chemotherapy.

Clinical trial identification

NCT01592825 (release date: 16.12.09).

Editorial acknowledgement

Legal entity responsible for the study

M. Vetter and E. Kantelhardt.

Funding

Wilhelm Roux Program of the Medical Faculty, Martin -Luther-University Halle-Wittenberg (grant number: FKZ 25/36) German Federal Ministry of Education and Research (grant number: Med FKZ 031A429).

Disclosure

C. Thomssen: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, AstraZeneca, Aurikamed, Daiichi Sankyo, Forum Sanitas, Gilead, Jörg Eickeler, Hexal, Lilly, Medupdate, MSD, Nanostring, Novartis, Onkowissen, Pfizer, Roche, Seagen, Vifor; Non-Financial Interests, Personal, Member: AGO Breast Committee, ASCO, DGGG (Germ Soc OB/GYN), DGS (Germ Soc Senology), DKG (Germ Cancer Soc), EORTC PathoBiomarker Group; Non-Financial Interests, Personal, Member of Board of Directors: AGO-B Breast Study Group; Non-Financial Interests, Personal, Officer: BIG; Non-Financial Interests, Personal, Invited Speaker: ESO; Non-Financial Interests, Personal, Steering Committee Member: ESMO. All other authors have declared no conflicts of interest.