Prognostic impact of tumor biological factors on survival in node-negative breast cancer

Tumor biological factors uPA, PAI-1, cathepsin D, S-phase fraction (SPF), MIB1 (Ki-67), p53, and HER-2/neu were assessed in 100 node-negative breast cancer patients. Their prognostic impact on disease-free (DFS) as well as overall survival (OS) was compared to that of traditional factors tumor size, grading, and steroid hormone receptor status. Antigen levels of uPA, its inhibitor PAI-1, and cathepsin D were determined in tumor tissue extracts by immunoenzymatic methods. SPF was determined by flow cytofluorometry, MIB1, p53, and HER-2/neu by immunohistochemistry in adjacent routinely formalin-fixed paraffin sections. Median follow-up in all patients still alive at time of analysis was 76 months. Univariate analysis determined PAI-1 (p = 0.0001), uPA (p = 0.0437), MIB1 (p = 0.0214), and SPF (p = 0.0248) as statistically significant prognostic factors for DFS. In contrast, tumor size, steroid hormone receptor status, grading, p53, HER-2/neu, and cathepsin. D failed to be of prognostic value. In multivariate analysis, including the statistically significant prognostic factors PAI-1, uPA, MIB1, and SPF, only PAI-1 (p = 0.0003, relative risk: 4.7) proved to be of independent statistical significance for DFS. Regarding OS, PAI-1 was the only statistically significant prognostic factor in univariate (p = 0.0001) as well as multivariate analysis (p = 0.0000, relative risk: 7.1). Thus, factors describing the invasive and metastatic capacity of tumor cells (uPA, PAI-1) and factors related to their proliferative activity (SPF, MIB1) provide valuable prognostic information in node-negative breast cancer patients.