Feasibility of Measuring the Prognostic Factors uPA and PAI-1 in Core Needle Biopsy Breast Cancer Specimens

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Tumor invasion factors urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor 1 (PAI-1) are American Society of Clinical Oncology (ASCO)–recommended cancer biomarkers for assessing whether node-negative breast cancer patients can forgo adjuvant chemotherapy ( 1 ). Numerous retrospective and prospective analyses ( 2 , 3 ), a multicenter prospective clinical trial ( 4 ), and a meta-analysis ( 5 ) have demonstrated the strong and statistically independent prognostic and predictive value of uPA and PAI-1 levels in node-negative breast cancer patients at the highest level of evidence. By applying established cutoff values for uPA (3 ng/mg protein) and PAI-1 (14 ng/mg protein) that were determined in primary tumor breast tissue extracts, we showed that uPA and PAI-1 levels distinguish between patients who are at low and high risk of disease recurrence ( 2 ). The St Gallen consensus panel 2005 recognized the validity of the uPA and PAI-1 data and suggested the use of uPA and PAI-1 levels as a predictor of endocrine resistance in node-negative breast cancer patients ( 6 ). Subsequently, the ASCO Tumor Marker Guidelines 2007 recommended routine clinical use of uPA and PAI-1 for assessing prognosis in patients with newly diagnosed node-negative breast cancer ( 1 ).