35P Adjuvant Chemotherapy in Node-Negative (N0) Breast Cancer: Routine Upa/Pai-1 Determination

Abstract

ABSTRACT More than 70% of patients with primary node-negative breast cancer are treated with local therapy alone. Biomarkers are used to determine disease risk and, consequently, determine whether or not chemotherapy is needed. Urokinase plaminogen activator (uPA) and its inhibitor plasminogen activator inhibitor 1 (PAI-1) are proteases implicated in invasiveness of tumor. The clinical utility of these markers has been proven on the highest level of evidence (LOE-1) in node-negative breast cancer patients. They are ASCO–recommended cancer biomarkers since 2007 and French Cancer Society (INCA)-recommended since 2009. But clinical routine use is poorly developed. The purpose was to register adjuvant chemotherapy decisions by a multidisciplinary discussion using uPA/PAI-1 concentrations compared to conventional prognostic parameters. The study was performed between January 2010 and December 2011. It included 164 frozen breast cancer tissue for determination of uPA and PAI-1 levels by enzyme-linked immunosorbent assay (ELISA) at Marseille Laboratory. However, the assay required a fresh-frozen tissue sample, which was not always feasible (25% of cases) because of tumor size or technical problems. UPA concentration of ≤3 ng/mg total protein and PAI-1 concentration of ≤14 ng/mg total protein were classified as low risk and one elevated marker classified patient as high risk. Tissues were always excised more than 10 days post breast biopsy and were frozen in a delay of 30 to 60 min. Results were obtained in 10 days post excision. Parameters were prospectively registered: age, menopausal status, tumor size, histological grade, steroid hormone receptor, Her2 overexpression, KI67, vascular embolism. Sixty-six tumors were uPA/PAI-1 negative, 41 uPA + /PAI-1 + , 12 uPA + /PAI-1- and 45 uPA-/PAI-1+. In the first 120 patients, uPA/PAI-1 value was discordant with conventional parameters, with a lower or higher prognostic index in 13 and 40 cases respectively. In some cases, the multidisciplinary decisions do not follow this score because of patient age, HER2 overexpression, grade 1 and limit level of uPA/PAI-1. Clinical decisions will be discussed and clinical routine problems of treatment with implication of the patients explained. Disclosure All authors have declared no conflicts of interest.