Selection criteria for epirubicin-based adjuvant chemotherapy in node-negative breast cancer.
The management of node-negative breast cancer is problematic due to the lack of reliable prognostic para-meters that distinguish patients who benefit from adjuvant chemotherapy. Since surgery alone is curative in approximately 70% of these patients, clinicians are faced with the dilemma of possible overtreatment or undertreatment. As a compromise, traditional cyclophosphamide/methotrexate/fluorouracil (CMF) is administered rather than newer, potentially more effective regimens containing anthracyclines or taxanes. Invasion and metastasis of solid tumors require tumor-biologic factors that promote the dissolution of the surrounding tumor matrix and the basement membranes, and the serine protease urokinase-type plasminogen activator (uPA) and its inhibitor, plasminogen activator-inhibitor type 1 (PAI-1), play major roles in these invasive processes. Our laboratory and others have reported that determinations by enzyme-linked immunosorbent assay (ELISA) of uPA and PAI-1 concentrations in tumor tissue extracts reliably separate patients with node-negative breast cancer at very low risk of relapse even without chemotherapy from high-risk patients who urgently need intensive effective treatment in order to reduce increased mortality. By eliminating low-risk patients from study entry, these markers permit unbiased evaluation of newer anthracycline-containing regimens in high-risk patients with node-negative disease. A multicenter, transnational European study is currently underway to compare the efficacy of a regimen combining epirubicin and cyclophosphamide with the traditional CMF regimen in these patients, whose risk of relapse and death is similar to that of many patients with node-positive disease.
Jänicke
F
F
Universitaets-Frauenklinik Hamburg Universitaets-Klinikum Hamburg Eppendorf, Germany. jaenicke@uke.uni-hamburg.de
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D004797:Enzyme-Linked Immunosorbent Assay; D015251:Epirubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D018579:Patient Selection; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011379:Prognosis; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood
D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D015251:Epirubicin; D014568:Urokinase-Type Plasminogen Activator