Invasion factors Urokinasetype plasminogen activator uPA and plasminogen activator inhibitor type 1 PAI1

In a prospective study of 247 breast cancer patients, uPA and PAI-1 were found to be independent prognostic factors and lower levels of both antigens were linked to a low risk of relapse (93% disease-free survival at 3 years) in contrast to patients with high levels (55% disease-free survival at three years) (81). The roles of these markers were further evaluated in a pooled analysis of more than 8,000 patients with breast cancer and several multi-center prospective randomized trials in node-negative breast cancer patients. Low antigen levels of uPA and PAI-1 were found to be independently associated with a low risk of recurrence, whereas patients with elevated uPA/PAI-1 antigen levels carried an increased risk of disease recurrence and a benefit from adjuvant chemotherapy (82-84). High tumor levels of uPA and PAI-1 were also associated with resistance to tamoxifen therapy when used as first line therapy for metastatic hormone-positive breast cancer (85). A study in 898 breast cancer patients with HER2-positive tumors further suggested that uPA mRNA expression may also be an adverse prognostic indicator in HER2-positive tumors (86).

These data suggest low uPA/PAI-1 antigen levels may be used to avoid aggressive therapy in low grade node-negative breast cancer whereas high levels may also indicate poor response to hormonal therapy and may be an indication to use adjuvant chemotherapy. Currently the enzyme immunoassays using monoclonal antibodies to human uPA as the capture reagents are available commercially in both USA and Europe. To date however, only the assessment of ER, PR, and HER2 are recommended as initial work up (http://www.nccn.org/professionals).

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