Abstract P2-08-21: Stromal co-expression of urokinase-type plasminogen activator (uPA) and plasminogen activator Inhibitor (PAI-1) protein by IHC predicts poor disease outcome in endocrine-treated postmenopausal patients with receptor-positive early breast cancer

Abstract

Abstract Background Elevated levels of intratumoral uPA and PAI-1 in ELISA-based measurements are associated with a high recurrence risk and allow to identify patients who might particularly benefit from adjuvant chemotherapy. The clinical utility of ELISA-based protein analysis is, however, greatly limited by the requirement of fresh tumor tisssue. We have therefore evaluated in a large clinical trial patient cohort with long-follow-up whether immunohistochemical detection of uPA and PAI-1 in FFPE archived tumor samples is also able to identify women with poor prognosis. Patients and Methods 547 postmenopausal women with hormone receptor–positive, early breast cancer who had received at least 5 years of endocrine therapy in the prospectively designed ABCSG-06 trial, and in whom FFPE tumor tissue was available, were included in this analysis. uPA and PAI-1 protein expression was evaluated by immunohistochemistry, and correlated with distant-disease free (DDFS) and overall survival (OS). Results Stromal co-expression of uPA and PAI-1 was detected in 166 of 276 (60%) evaluable tumor samples and was weakly associated with tumor size (p=0.012, Chi Square test) but not with age, nodal status, grading, or receptor status. Women with intratumoral uPA/PAI-1 expression were more likely to have a shorter DDFS in multivariate analysis (HR for relapse p=1.870; 95% CI 1.184-2.955; p=0.007 Cox regression analysis) and and OS (adjusted HR for death p=1.291; 95% CI 0.928-1.795; p=0.129) than women without. After a median follow-up of 10 years, women with uPA/PAI-1-positive tumors experienced a significantly shorter DDFS (p<0.0001 log rank test) and OS (p=0.020). Conclusions Stromal co-expression of uPA and PAI-1 in breast cancer samples predicts poor DDFS and OS in postmenopausal women with hormone-receptor positive early-stage breast cancer who receive endocrine therapy. Citation Format: Singer CF, Filipits M, Jahn S, Abete L, Jakesz R, Greil R, Bauernhofer T, Kwasny W, Seifert M, Fitzal F, Schmitt M, Moinfar F, Gnant M. Stromal co-expression of urokinase-type plasminogen activator (uPA) and plasminogen activator Inhibitor (PAI-1) protein by IHC predicts poor disease outcome in endocrine-treated postmenopausal patients with receptor-positive early breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-21.