Impact of guideline-based use of uPA/PAI-1 on patient outcome in intermediate-risk early breast cancer

Abstract

The purpose of this study was to evaluate the influence of guideline-based prospective use of uPA/PAI-1 on clinical outcome in an intermediate-risk cohort of breast cancer patients. We analyzed 381 consecutive primary breast cancer patients (2003-2011) at the breast center Ostbayern meeting the following criteria: M0/N0/estrogen receptor (ER)+/G2. Clinical-pathological data, uPA/PAI-1, and follow-up data were collected. Decisions for adjuvant chemotherapy were made upon consideration of prospectively measured uPA/PAI-1. Observed disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier estimates. Using guideline-based analysis of uPA/PAI-1, treatment with adjuvant chemotherapy was avoided in 86.5 % of patients with low uPA/PAI-1, i.e., 38.8 % of the total patient collective. Median follow-up was 52.5 months. Five-year relapse-free survival in intermediate-risk patients (N0, G2) without chemotherapy was 99 %. Five-year overall survival including all causes of death was 95 %. By using uPA/PAI-1, adjuvant chemotherapy can be avoided in a major part of patients with intermediate-risk breast cancer. Nevertheless, DFS and OS of these patients at 5 years remain excellent. The potential, but hardly measurable, benefit of adjuvant chemotherapy has to be set in contrast with its associated side effects and increased morbidity. Patients with high uPA/PAI-1 show benefit from chemotherapy. In this subgroup, a very good OS was observed as well. These findings strongly support the use of uPA/PAI-1 together with clinic-pathological parameters as an evidence-based, clinically relevant and inexpensive decision tool in the routine of a breast center.

Decision impact and feasibility of different ASCO-recommended biomarkers in early breast cancer: Prospective comparison of molecular marker EndoPredict and protein marker uPA/PAI-1

“…EPclin and uPA/PAI-1 have been validated for risk stratification of patients with endocrine sensitive early breast cancer and have been used already for some time in clinical routine. The risk stratification performed in the context of the present study by uPA/PAI-1 (46% low risk, 54% high risk) and EPclin (63% low risk, 37% high risk) is consistent with published data from other retrospective, monocentric surveys; recently, Kolben et al reported about 381 intermediate-risk patients, of which 45% were uPA/PAI-1 low risk and 55% were uPA/PAI-1 high risk [ 24 ]. Müller et al report a EPclin low-risk group of 48% in a cohort of 167 defined tumors in which smaller tumors (pT1a/b) were under-represented compared to the present study [ 20 ].…”

Assessment of Ki67 and uPA/PAI-1 expression in intermediate-risk early stage breast cancers

“…Previous studies have shown that the use of uPA/PAI-1 combined with a clinicopathological parameter, such as vascular invasion, is extremely helpful for yielding prognostic data [ 24 ]. We identified a correlation between Ki67 and uPA/PAI-1 status in grade II tumours, in agreement with Kolben et al [ 25 ], although we lack an explanation for this correlation.…”

“…This rate of indication for adjuvant chemotherapy (i.e. 6%) was similar to that in a previous report [ 27 ], but lower than the rate of 13% reported by Kolben et al [ 25 ]. However, the cut-off value for Ki67 in those studies was different from that in the current study (10–15% in Kolben et al and Vénat-Bouvet et al vs. 20% in our study).…”

uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy

“…We observed that the expression of these proteins in pre-treatment tumor biopsies could be used to identify patients with a high probability of death and to distinguish them from patients with low risk. Many studies in breast cancer patients, have establish SERPINE1 and uPA as suitable markers for therapy decision-making in patients with early lymph-node negative breast cancer [ 143 - 146 ]. We expect that these markers will be increasingly studied in the near future to establish if they could also be used in HNSCC patients for helping treatment decision making, especially to identify those patients with a high risk of metastasis who could be treated with adjuvant chemotherapy or chemo-radiation.…”