N. Harbeck et al., Risk group discrimination in node-negative breast cancer using invasion and proliferation markers: 6-year median follow up, BR J CANC, 80(3-4), 1999, pp. 419-426
Factors reflecting two major aspects of tumour biology, invasion (urokinase
-type plasminogen activator (uPA), plasminogen activator inhibiter (PAI-1),
cathepsin D) and proliferation (S-phase fraction (SPF), Ki-67, p53, HER-2/
neu), were assessed in 125 node-negative breast cancer patients without adj
uvant systemic therapy. Median follow-up time was 76 months. Antigen levels
of uPA, PAI-1 and cathepsin D were immunoenzymatically determined in tumou
r tissue extracts. SPF and ploidy were determined flow-cytometrically, Ki''
'-67, p53, and HER-2/neu immunohistochemically in adjacent paraffin section
s. Their prognostic impact on disease-free (DFS) and overall survival (OS)
was compared to that of traditional factors (tumour size, grading, hormone
receptor status). Univariate analysis determined PAI-1 (P < 0.001), UPA (P
= 0.008), cathepsin D (P = 0.004) and SPF (P = 0.023) as significant for DF
S. All other factors failed to be of significant prognostic value. In a Cox
model, only PAI-1 was significant for DFS (P < 0.001, relative risk (RR) 6
.2). In CART analysis for DFS, the combination of PAI-1 and UPA gave the be
st risk group discrimination. For OS, PAI-I, cathepsin D, tumour size and p
loidy were statistically significant in univariate, but PAI-1 was the only
independently significant factor in Cox analysis (P < 0.001, RR 8.9). In pa
rticular, this analysis shows that PAI-1 is still a strong and independent
prognostic factor in node-negative breast cancer after extended 6-year medi
an follow-up.