Risk-group discrimination in node-negative breast cancer using invasion and proliferation markers: 6-year median follow-up

• Published in: British Journal of Cancer Vol. 80; no. 3-4; pp. 419 - 426
• Main Authors: HARBECK, N, DETTMAR, P, THOMSSEN, C, BERGER, U, ULM, K, KATES, R, HÖFLER, H, JÄNICKE, F, GRAEFF, H, SCHMITT, M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.05.1999
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor - metabolism; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Confidence Intervals; Female; Follow-Up Studies; Gynecology. Andrology. Obstetrics; Humans; Lymph Nodes - pathology; Mammary gland diseases; Medical sciences; Middle Aged; Multivariate Analysis; Neoplasm Invasiveness; Prognosis; Proportional Hazards Models; Prospective Studies; Regular; Retrospective Studies; Risk Factors; Tumors; Human; Immunohistochemistry; Cell proliferation; u-Plasminogen activator; Carcinoma; Prognosis; Serine endopeptidases; Enzyme; Risk; Malignant tumor; Invasion; Pathology; Mammary gland diseases; Peptidases; Plasminogen activator inhibitor 1; Follow up study; S Phase; Hydrolases; Female; Aspartic endopeptidases; Cathepsin D; Mammary gland; ELISA assay
• ISSN: 0007-0920; 1476-5381; 1532-1827
• DOI: 10.1038/sj.bjc.6690373

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 adjuvant systemic therapy. Median follow-up time was 76 months. Antigen levels of uPA, PAI-1 and cathepsin D were immunoenzymatically determined in tumour tissue extracts. SPF and ploidy were determined flow-cytometrically, Ki"'-67, p53, and HER-2/neu immunohistochemically in adjacent paraffin sections. 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 DFS. 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 best risk group discrimination. For OS, PAI-1, cathepsin D, tumour size and ploidy were statistically significant in univariate, but PAI-1 was the only independently significant factor in Cox analysis (P < 0.001, RR 8.9). In particular, this analysis shows that PAI-1 is still a strong and independent prognostic factor in node-negative breast cancer after extended 6-year median follow-up.