Plasminogen activator inhibitor-1 (PAI-1) is not related to response to neoadjuvant chemotherapy in breast cancer

Abstract

Summary There is no information available on the relation between response to chemotherapy and the high-risk phenotype assessed by uPA and/or PAI-1. The clinical situation of neoadjuvant chemotherapy provides a means of rapidly assessing the sensitivity of the primary tumour to cytotoxic drug regimens. The goal of the study was to assess prospectively the predictive value of PAI-1 for response to first-line chemotherapy. PAI-1 concentration was measured on hypertonic cytosolic extracts (0.4 M potassium chloride) by ELISA before chemotherapy on a drill biopsy sample of the tumour in 69 T2 and T3 breast cancer patients (median age 46 years). Oestrogen receptor (ER) (51% ER+), progesterone receptor (PR) (58% PR+), S-phase (median 4.0%) and ploidy were also assessed in the majority of cases. The clinical response to treatment was evaluated after four cycles of FAC or FEC regimen (5-fluorouracil, epidoxorubicin or doxorubicin and cyclophosphamide) (one cycle every 4th week). PAI-1 could be assayed in 29 post-chemotherapy surgical samples. The objective response rate (complete response plus partial response) was 59% (41 out of 69). PAI-1 expressed as gram of tissue (range 19-2370 ng g-1 tissue) was highly correlated (r = 0.98) to PAI-1 expressed as mg protein (range 0.5-68 ng mg-1 protein). No correlation between PAI-1 level and response could be observed, with any cut-off. The post-and pre-chemotherapy PAI-1 levels were correlated (r = 0.66). Of all biological parameters, only high S-phase (cut-off 5%) was slightly correlated (X2 = 3.91, P = 0.05) to response. These data suggest that PAI-1 is not a predictive marker of response to chemotherapy in breast cancer and that its level is not altered by neoadjuvant chemotherapy.

Predictive Impact of Urokinase-Type Plasminogen Activator

“…A recent study focused on the predictive value of uPA and PAI-1 in patients treated with neo-adjuvant chemotherapy (12), and another had addressed the efficacy of systemic therapy in patients with advanced breast cancer (13). The results of those studies may not be simply translated to the adjuvant setting.…”

Invasionsfaktoren uPA/PAI‐1 im Tumorgewebe bei Patientinnen mit primärem Mammakarzinom: Von Forschungsergebnissen zur klinischen Anwendung am Beispiel der NNBC 3-Europe-Studie

“…Bezüglich einer neoadjuvanten Chemotherapie gibt es Daten von einem kleinen Kollektiv (n = 69), die keine Korrelation zwischen den PAI-1-Werten vor der Therapie und dem klinischen Ansprechen auf die anthrazyklinhaltige Chemotherapie zeigten [51]. Bezüglich der palliativen Therapie konnte gezeigt werden, dass metastasierte Patientinnen mit hohen Werten an uPA und PAI-1 im Primärtumor deutlich schlechter auf palliative endokrine Tamoxifentherapie ansprachen als Patientinnen mit niedrigen Werten [52].…”

Clinical Relevance of the Plasminogen Activator Inhibitor Type1 – a Multifaceted Proteolytic Factor

“…Prospective evidence for the predictive impact of PAI-1 is still scarce. Pierga et al [31] did not observe a correlation between PAI-1 in primary tumor core biopsies and local response to anthracycline-containing neoadjuvant chemotherapy. PAI-1 tumor levels were not altered by chemotherapy; however, the authors did not present data on correlation of PAI-1 with patient outcome [31].…”

“…Pierga et al [31] did not observe a correlation between PAI-1 in primary tumor core biopsies and local response to anthracycline-containing neoadjuvant chemotherapy. PAI-1 tumor levels were not altered by chemotherapy; however, the authors did not present data on correlation of PAI-1 with patient outcome [31]. In the 'Chemo N 0 ' trial, node-negative breast cancer patients with high PAI-1 and/or uPA did benefit from adjuvant CMF chemotherapy [27].…”