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References 1. Harris L , Fritsche H , Mennel R , et al . American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer . J Clin Oncol . 2007 ; 25 ( 33 ): 5287 – 5312 . 2. Harbeck N , Thomssen C , Berger U , et al . Invasion marker PAI-1 remains a strong prognostic factor after long-term follow-up both for primary breast cancer and following fi rst relapse . Breast Cancer Res Treat . 1999 ; 54 (2) : 147 – 157 . 3. Annecke K , Schmitt M , Euler U , et al . uPA and PAI-1 in breast cancer: review of their clinical utility and current validation in the prospective NNBC-3 trial . Adv Clin Chem. 2008 ; 45 : 31 – 45 . 4. Janicke F , Prechtl A , Thomssen C , et al . Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identifi ed by urokinase-type plasminogen activator and plasminogen activator Feasibility of Measuring the Prognostic Factors uPA and PAI-1 in Core Needle Biopsy Breast Cancer Specimens

10539 Background: The ASCO guidelines recommend the validated invasion markers uPA/PAI-1 (Harris, JCO 2007) for routine risk assessment in N0 breast cancer. Also, St.Gallen-adapted clinico-patholog...

544 Background: ASCO Tumor Marker Guidelines 2007 recommended clinical routine use of the invasion markers uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 for risk assessment in N0 breast cancer pts (Harris et al, J Clin Oncol. 2007;25:5287). Ten-year follow-up data of the confirmatory prospective clinical uPA/PAI-1 trial (CHEMO-N0) will be presented at the ASCO 2009 Meeting (Harbeck et al.). We conducted a further prospective trial (NNBC 3-Europe) addressing the direct comparison between risk-assessment by uPA/PAI-1 (UP) and clinico-pathological factors (C), and optimization of adjuvant chemotherapy for high-risk N0 pts: FEC*3-Doc*3 vs. standard FEC*6. Methods: From December 2002 to January 2009, 4,040 pts were recruited by 151 centres. For uPA and PAI-1 ELISA, tumors samples were snap frozen und processed. Risk assessment was based on grade and in G2 tumors, either by UP or by a St. Gallen adapted C algorithm. High-risk pts were randomized for adjuvant chemotherapy. All laboratories took part in central quality assurance (QA) for uPA/PAI-1 determination. Results: Risk assessment was performed for 1,590 pts based on C and for 2,445 pts based on UP. End of accrual was planned when 2,572 high risk pts were randomised for chemotherapy and thus ends Jan 31, 2009. Current status shows 1,291 high-risk pts in the FEC-Doc and 1,294 in the FEC arm. In the low-risk arm, 1,450 pts have endocrine therapy, only. By both risk stratifications, 42% of the G2 tumors were assigned as low risk, but in total, more pts were classified as low-risk by UP (39%) than by C (31%). Median uPA level were at 2.40 ng/mg protein (below cutoff), median PAI-1 at 15.9 (above cutoff). In the QA programm, mean coefficients of variations are 12% for uPA and PAI-1 determination. Conclusions: The prospective biomarker trial using uPA/PAI-1 has just ended accrual with more than 4,000 patients. Routine uPA/PAI-1 determination is reliable and feasible even in core needle specimens. Using tumor grade and uPA/PAI-1, adjuvant chemotherapy may be avoided in about 39% of N0 breast cancer pts. Cooperation: EORTC Patho-Biology Group, AGO Breast Group, GBG, Unrestricted grants by Sanofi-Aventis, Pfizer, American Diagnostica, Martin-Luther-Universitaet Halle-Wittenberg. [Table: see text]

Abstract #1092 The American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer suggests the use of the invasion markers urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 for risk assessment (Harris et al. JCO 25:5287). In 2003, we launched the NNBC 3-Europe trial for node negative breast cancer patients with the following questions: 1) Comparison of risk-assessment: invasion markers uPA/PAI-1 vs. clinico-pathological factors. 2) Comparison of adjuvant FEC-Docetaxel (anthracycline-taxane sequence) vs. standard FEC in high-risk patients? 3) Use of fresh tissue sampling was necessary within this trial. Quality assurance for the testing procedure was prospectively performed. Study Design: Risk assessment is performed either by clinico-pathological factors or by uPA/PAI-1. High-risk patients receive adjuvant chemotherapy according to randomisation. Adjuvant endocrine therapy is given according to guidelines. All laboratories take part on the central quality assurance program. In addition, we also analyzed feasibility of uPA/PAI-1 determination from core needle biopsies. Results:To date, from 131 participating centres, 3060 patients have been registered for the trial. Biological risk assessment was performed in 2000 patients. Using both tumor grade and uPA/PAI-1 results, the low-risk group comprises 38% of the patients, whereas 62% were considered high-risk and randomized for the adjuvant chemotherapy question. All centres show a well established collaboration with the pathologists who were responsible for histological confirmation of the frozen tumor samples and for the weekly shipment to the central labs. Mean coefficients of variation (CV) for between-lab and within-lab are 12% for uPA and PAI-1. Using core needle biopsies (n=36) in comparison to larger tumor pieces, we found a rather good correlation (r=0.89; p Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1092.

Correction to: Oncogene (2005) 24, 650–661. doi:10.1038/sj.onc.1208234 Published online 8 November 2004 Since publication of the above manuscript, the authors have identified an error in the figure legend of Figure 3a. The legend should read: ‘(a) Inhibition of proteasome function.’