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Data from meta-analyses have shown taxane-containing therapies to be superior to anthracycline-based treatments for high-risk breast cancer.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/m(2)) and cyclophosphamide (600 mg/m(2)) every 3 weeks (q3w), followed by 4× docetaxel (100 mg/m(2)) q3w (EC-Doc arm), or 6× epirubicin (60 mg/m(2)) and 5-fluorouracil (500 mg/m(2)) on days 1 and 8 and cyclophosphamide (75 mg/m(2)) on days 1-14, q4w (FEC arm). We compared both arms with respect to toxicity and feasibility.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).The sequential anthracycline-taxane regimen is a well-tolerated and feasible alternative to FEC120 therapy.Metaanalysen zeigten die Überlegenheit von taxanhaltigen Chemotherapien gegenüber rein anthrazyklinbasierten Therapieregimen bei Hochrisiko-Mammakarzinompatientinnen.Die ADEBAR-Studie, als multizentrische Phase-III-Studie, randomisierte nodalpositive Mammakarzinompatientinnen entweder in den sequentiellen Anthrazyklin-Taxan-Arm oder in den FEC120-Arm. Die Patientinnen erhielten 4× Epirubicin (90 mg/mHämatologische Toxizität fand sich signifikant häufiger im FEC-Arm. Febrile Neutropenie trat bei 11,3% der Patientinnen im FEC-Arm auf sowie bei 8,4% der Patientinnen im EC-Doc-Arm (p = 0,027). Schwere nicht-hämatologische Nebenwirkungen Grad 3/4 traten in beiden Armen selten auf. Aufgrund von Toxizitäten musste die Therapie bei 3,7% der Patientinnen im EC-Doc-Arm sowie bei 8,0% der Patientinnen im FEC-Arm abgebrochen werden (p = 0,0009).Das sequentielle Anthrazyklin-Taxan-Regime ist eine gut verträgliche Alternative zu FEC120.

Cyclophosphamide, methotrexate and 5-fluorouracile (CMF)-based chemotherapy for adjuvant treatment of breast cancer reduces the risk of relapse. In this exploratory study, we tested the feasibility of identifying molecular markers of recurrence in CMF-treated patients. Using Affymetrix U133A GeneChips, RNA samples from 19 patients with primary breast cancer who had been uniformly treated with adjuvant CMF chemotherapy were analyzed. Two supervised class prediction approaches were used to identify gene markers that can best discriminate between patients who would experience relapse and patients who would remain disease-free. An additional independent validation set of 51 patients and 21 genes were analyzed by quantitative RT-PCR. Applying different algorithms to evaluate our microarray data, we identified two gene expression signatures of 21 and 12 genes containing eight overlapping genes, that predict recurrence in 19 cases with high accuracy (94%). Quantitative RT-PCR demonstrated that six genes from the combined signatures (CXCL9, ITSN2, GNAI2, H2AFX, INDO, and MGC10986) were significantly differentially expressed in the recurrence versus the non-recurrence group of the 19 cases and the independent breast cancer patient cohort (n = 51) treated with CMF. High expression levels of CXCL9, ITSN2, and GNAI2 were associated with prolonged disease-free survival (DFS) (P = 0.029, 0.018 and 0.032, respectively). When patients were stratified by combined CXCL9/ITSN2 or CXCL9/FLJ22028 tumor levels, they exhibited significantly different disease-free survival curves (P = 0.0073 and P = 0.005, respectively). Finally, the CXCL9/ITSN2 and CXCL9/FLJ22028 ratio was an independent prognostic factor (P = 0.034 and P = 0.003, respectively) for DFS by multivariate Cox analysis in the 70-patient cohort. Our data highlight the feasibility of a prognostic assay that is applicable to therapeutic decision-making for breast cancer. Whether the biomarker profile is chemotherapy-specific or whether it is a more general indicator of bad prognosis of breast cancer patients remains to be explored.

1081 Background: Based on meta-analytic evidence, taxane containing adjuvant chemotherapy has been established as standard treatment in breast cancer (BC). However, in the MA-21 study, adriamycin-cyclophosphamide, followed by paclitaxel was significantly inferior FEC120. We prospectively compared a sequential epirubicin-docetaxel chemotherapy regimen to FEC120. Methods: The ADEBAR study was a multicenter phase III trial (n=1502) to evaluate whether pts with > 3 axillary lymph node metastases BC benefit from a sequential anthracycline-docetaxel regimen (E90C–D: 4 cycles epirubicin [E] 90 mg/m2 plus cyclophosphamide [C] 600 mg/m2 q21d followed by 4 cycles docetaxel [D] 100mg/m2 q21d) compared to dose-intensive anthracycline-containing polychemotherapy (FE120C: 6 cycles E 60 mg/m² d 1+8, 5-FU 500mg/m² d 1+8 and C 75 mg/m² d 1-14, q4w). The observation time (median – 95%CI) was 49.5 (47.4 – 51.3) m. Results: Treatment was stopped prematurely in 3.7% of the pts in the E90C–D arm and in 8.0% in the FE120C arm due to toxicity (p=0.0009). Antibiotic treatment was given in 10.4% (E90C–D) vs. 19.7% (FE120C), G-CSF support in 39.2% vs 61.4 % and erythropoietin stimulation in 8.7% vs. 20.0%, respectively (p

1072 Background: Besides established prognostic factors such as tumor size or nodal status, individual host factors of the patient such as obesity, physical activity and diet seem to modulate the course of breast cancer (BC) as well. However, the specific impact of weight change during adjuvant chemotherapy remains unclear. The aim of this analysis was to evaluate the influence of weight change during chemotherapy on BC survival in a large, multi-center prospectively randomized trial. Methods: The ADEBAR trial compares two anthracycline based adjuvant chemotherapy regimen in patients (pts) with lymph node positive ( > 3 positive) early BC: 4 x epirubicin (E) 90 mg/m2 + cyclophosphamide (C) 600 mg/m2 q3w followed by 4 x docetaxel 100 mg/m2 q3w versus 6 x E 60 mg/m2 + 5-FU 500 mg/m2 d1+d8 and C 75 mg/m2 d1-14 q4w. Weight was measured before each cycle. The weight before the 1st and the 6th cycle was assessed. Significant weight change was defined as increase or decrease of > 5% of the initial weight. Overall survival (OS), disease free survival (DFS), and BC specific survival (BCSS) were assessed by Kaplan-Meier analysis. Results: In total, 1502 pts were included in the study. 1177 of them completed 6 cycles of chemotherapy. Out of the 350 pts (29.7%) who changed weight 142 pts (12.1%) lost and 208 pts (17.7 %) gained weight. There was a significant correlation between weight change and menopausal status (p 5% showed a significantly worse outcome with respect to OS (p = 0.0028) and BCSS (p = 0.0258). A difference in DFS was not observed (p = 0.1917). The difference in OS was limited to pts who lost weight (p = 0.0008), whereas pts with weight gain have no significant different OS (p = 0.1246) in comparison to pts with constant weight. Conclusions: Our results suggest that weight loss during anthracycline-based treatment of early stage BC is associated with poorer OS. While weight normalization has shown beneficial effects in lifestyle intervention trials, patients should be advised not to lose weight during chemotherapy.