Clinical relevance of invasion factors urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 for individualized therapy decisions in primary breast cancer is greatest when used in combination.
OBJECTIVE
A strong prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor and plasminogen activator inhibitor type 1 (PAI-1) as individual factors is well established in breast cancer. The improvement in clinical risk assessment gained by combining these factors is evaluated here.


METHODS
uPA and PAI-1 levels were prospectively measured by enzyme-linked immunosorbent assay in tumor tissue extracts of 761 patients with primary breast cancer.


RESULTS
In the clinically important subgroup of node-negative patients without adjuvant systemic therapy (n = 269; median follow-up, 60 months), the clinical value of testing both uPA and PAI-1 is demonstrated. The criterion either or both high identifies with high sensitivity the patients at high relapse risk while keeping more than half in the low-risk group. uPA/PAI-1 is the strongest predictor of disease-free survival and overall survival; patients with high uPA/PAI-1 have an increased relapse risk (P <.001; relative risk, 4.8; 95% confidence interval [CI], 2.5 to 9.1), in particular for early relapse. Even within risk groups stratified by established criteria (nodal or menopausal status, tumor size, grade, or steroid hormone receptors), uPA/PAI-1 provides significant risk group discrimination. In the whole collective, the significant interaction between uPA/PAI-1 and adjuvant systemic therapy suggests a benefit from adjuvant therapy in high-risk patients as defined by uPA/PAI-1.


CONCLUSIONS
The clinical relevance of the two tumor-invasion factors uPA and PAI-1 is greatest when they are used in combination. The particular combination of uPA and PAI-1 (both low v either or both high) is superior to either factor alone and supports risk-adapted individualized therapy decisions.
Harbeck
Nadia
N
Clinical Research Group, Department of Obstetrics and Gynecology, Technical University of Munich, Munich, Germany. nadia.harbeck@lrz.tum.de
Kates
Ronald E
RE
Schmitt
Manfred
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003657:Decision Making; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010347:Patient Care Planning; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
D017395:Plasminogen Activator Inhibitor 1; D014568:Urokinase-Type Plasminogen Activator