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An imbalance in c-Met expression between tumour and surrounding normal tissue is associated with an aggressive DCIS phenotype. Moreover, c-Met and HGF/SF may contribute to tumour development by different means than those controlled by Her2/neu.

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Background: Data from meta-analyses have shown taxane-containing therapies to be superior to anthracycline-based treatments for high-risk breast cancer. Patients and Methods: The ADEBAR trial was a multicenter phase III trial in which patients with lymph node-positive breast cancer were prospectively randomized for either sequential anthracycline-taxane or FEC120 therapy. Patients received 4× epirubicin (90 mg/m²) and cyclophosphamide (600 mg/m²) every 3 weeks (q3w), followed by 4× docetaxel (100 mg/m²) q3w (EC-Doc arm), or 6× epirubicin (60 mg/m²) and 5-fluorouracil (500 mg/m²) on days 1 and 8 and cyclophosphamide (75 mg/m²) on days 1–14, q4w (FEC arm). We compared both arms with respect to toxicity and feasibility. Results: Hematological toxicity was found significantly more often in the FEC arm. Febrile neutropenia was seen in 11.3% of patients in the FEC arm and in 8.4% of patients in the EC-Doc arm (p = 0.027). Non-hematological side effects of grade 3/4 were rarely seen in either arm. Therapy was terminated due to toxicity in 3.7% of the patients in the EC-Doc arm and in 8.0% of the patients in the FEC arm (p = 0.0009). Conclusion: The sequential anthracycline-taxane regimen is a well-tolerated and feasible alternative to FEC120 therapy.

Background:Taxane-containing adjuvant chemotherapy has been established as standard treatment in node-positive breast cancer. This study compared efficacy and tolerability of epirubicin (E)/cyclophosphamide (C) followed by docetaxel (Doc) with a dose-dense 5-fluorouracil (F)+E+ C regimen.Methods:The ADEBAR study was a randomised phase III trial for women with primary invasive breast cancer and ⩾4 metastatic axillary lymph nodes (n=1364). Treatment consisted of four 21-day cycles of E plus C, followed by four 21-day cycles of Doc (EC-Doc), or six 28-day cycles of E plus F plus C (FEC120).Results:Disease-free survival (DFS) was similar in the two treatment arms as shown by multivariate Cox regression adjusted for other prognostic factors (EC-Doc vs FEC120, hazard ratio (HR): 1.087; 95% confidence interval (CI): 0.878–1.346, P=0.444). In addition, there was no significant difference in overall survival (OS) between the two groups (HR: 0.974; 95% CI: 0.750–1.264, P=0.841). Haematologic toxicity was more common in FEC120 recipients; non-haematologic toxicities occurred more frequently in the EC-Doc arm. The serious adverse event rate was significantly higher in the FEC120 group (29.7% vs 22.5%).Conclusions:EC-Doc provides a feasible and effective alternative therapy option to FEC120 with a different safety profile in this high-risk breast cancer cohort.

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10503 Background: Feasibility of risk assessment in node negative breast cancer using the invasion markers urokinase-type plasminogen activator uPA and its inhibitor PAI-1 has been demonstrated in several prospective and retrospective studies and in a large meta analysis. Patients with low uPA and/or PAI-1 concentrations in tumor tissue levels have an excellent 5-year overall survival (>95%) even without any adjuvant therapy. Use of these molecular markers may spare adjuvant chemotherapy in approximately one half of node-negative breast cancer patients. Particulary, patients with an intermediate grade tumor can easily be differentiated in low and high risk. In addition, patients with high uPA and/or PAI-1 level seem to benefit from adjuvant chemotherapy. The NNBC-3-Europe trial seeks to answer two questions: 1. Is risk assessment by molecular markers uPA/PAI-1 superior to that by clinico-pathological factors regarding identification of low-risk patients? 2. Is adjuvant chemotherapy with anthracycline-taxane sequence (FEC-Docetaxel) superior to standard FEC in high-risk patients? Methods: In the NNBC-3-Europe trial, participating centres opt to either perform risk estimation by clinico-pathological factors or by the uPA and PAI-1 concentration in tumor tissue biopsies. Low-risk patients will be observed without adjuvant chemotherapy. High-risk patients are randomised based on the kind of adjuvant chemotherapy. Patients with steroid hormone receptor positive tumors receive adequate endocrine therapy. Results: Of the first 506 patients in the study arm with molecular risk assessment, 62 had a grade 1 tumors, and 184 had grade 3 tumors. Among grade 2 tumors (n = 260), 87 had low uPA/PAI-1. 173 patients presented with high levels. About 30% of the patients were allocated to the low-risk group using uPA/PAI-1. Conclusions: An adjuvant chemotherapy trial based on uPA/PAI-1 determination in the primary tumor is feasible in a multicentre setting. Applying these molecular markers for risk assessment, at this stage of the study, adjuvant chemotherapy could be spared in almost one third of N0 patients. It is performed in association with the EORTC PathoBiology Group Receptor und the German AGO Breast Group. [Table: see text]