Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 523
© 2004 American Society of Clinical Oncology

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Abstract

Pooled analysis (n=8,377) evaluates predictive impact of uPA and PAI-1 for response to adjuvant therapy in breast cancer

Technical University of Munich, Munich, Germany; ErasmusMC, Rotterdam, Netherlands

523

Background: The prognostic impact of invasion factors uPA and PAI-1 in primary breast cancer has been demonstrated at the highest level of evidence by the prospective clinical Chemo N0 trial and a large pooled analysis. Recent results also suggested a predictive impact of these factors. Methods: In order to validate the predictive impact of uPA and PAI-1 in primary breast cancer, a pooled analysis was performed on 18 observational data sets (n=8,377) provided by members of the EORTC Receptor and Biomarker Group. uPA and PAI-1 were determined in primary tumor tissue extracts using ELISAs and ranked by center. Decisions to administer adjuvant therapy did not utilize uPA/PAI-1. Median follow-up was 79 months. Results: Time-varying survival analysis stratified by center showed that adjuvant chemotherapy (CT) was associated with an enhanced benefit (HR 0.60, CI 0.41–0.87) in patients with high uPA/PAI-1, particularly for preventing relapses during the first 3 years -in addition to its benefit in the cohort as a whole. In the 0–3 node subgroup, the enhanced benefit was also strong (HR 0.51, CI 0.31–0.85). No interaction between adjuvant endocrine therapy (ET) and uPA/PAI-1 was found in Cox analysis. However, a low-risk subgroup of N0, hormone-receptor positive, low uPA/PAI-1 patients receiving ET was identified with 10-year OS and DFS of about 92 %. Conclusions: A strong and independent predictive impact of uPA and PAI-1 regarding adjuvant chemotherapy in breast cancer was validated in this pooled analysis. However, we did not see evidence for a subgroup defined by uPA and PAI-1 for which adjuvant endocrine therapy should not be given. Our data suggest that all patients with high uPA/PAI-1 -regardless of their nodal status -should receive adjuvant chemotherapy. Moreover, in patients where the decision between endocrine and chemo-endocrine therapy is clinically open, uPA and PAI-1 could provide decisive evidence.

Author Disclosure

Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration American Diagnostica, Inc. American Diagnostica, Inc.

Abstract presentation from the 2004 ASCO Annual Meeting