uPA and PAI-1 as biomarkers in breast cancer: validated for clinical use in level-of-evidence-1 studiesReport as inadecuate




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Breast Cancer Research

, 16:428

Recent advances in breast cancer treatment

Abstract

Urokinase plasminogen activator uPA is an extracellular matrix-degrading protease involved in cancer invasion and metastasis, interacting with plasminogen activator inhibitor-1 PAI-1, which was originally identified as a blood-derived endogenous fast-acting inhibitor of uPA. At concentrations found in tumor tissue, however, both PAI-1 and uPA promote tumor progression and metastasis. Consistent with the causative role of uPA and PAI-1 in cancer dissemination, several retrospective and prospective studies have shown that elevated levels of uPA and PAI-1 in breast tumor tissue are statistically independent and potent predictors of poor patient outcome, including adverse outcome in the subset of breast cancer patients with lymph node-negative disease. In addition to being prognostic, high levels of uPA and PAI-1 have been shown to predict benefit from adjuvant chemotherapy in patients with early breast cancer. The unique clinical utility of uPA-PAI-1 as prognostic biomarkers in lymph node-negative breast cancer has been confirmed in two independent level-of-evidence-1 studies that is, in a randomized prospective clinical trial in which the biomarker evaluation was the primary purpose of the trial and in a pooled analysis of individual data from retrospective and prospective studies. Thus, uPA and PAI-1 are among the best validated prognostic biomarkers currently available for lymph node-negative breast cancer, their main utility being the identification of lymph node-negative patients who have HER-2-negative tumors and who can be safely spared the toxicity and costs of adjuvant chemotherapy. Recently, a phase II clinical trial using the low-molecular-weight uPA inhibitor WX-671 reported activity in metastatic breast cancer.

Abbreviations5-FUfluorouracil

CIconfidence interval

CMFcyclophosphamide-methotrexate-5 fluorouracil

CVcoefficient of variation

ECMextracellular matrix

ELISAenzyme-linked immunosorbent assay

EQAexternal quality assessment

ERestrogen receptor

HER-2human epidermal growth factor receptor 2

HGFhepatocyte growth factor

HRhazard ratio

LDLRlow-density lipoprotein receptor

LOE-1level of evidence 1

LRPlow-density lipoprotein receptor-related protein

MMPmatrix metalloprotease

PAI-1plasminogen activator inhibitor-1

PFSprogression-free survival

RRrelative risk

uPAurokinase plasminogen activator

uPARurokinase plasminogen activator receptor

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Author: Michael J Duffy - Patricia M McGowan - Nadia Harbeck - Christoph Thomssen - Manfred Schmitt

Source: https://link.springer.com/







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