Abstract S3-4: Ten year follow-up analysis of intense dose-dense adjuvant ETC (epirubicin (E), paclitaxel (T) and cyclophosphamide (C)) confirms superior DFS and OS benefit in comparison to conventional dosed chemotherapy in high-risk breast cancer patients with ≥ 4 positive lymph nodes.

Background: The 5-year analysis of adjuvant chemotherapy with intense dose-dense (IDD) ETC had shown a significant improved DFS (HR 0.72; p Patients and Methods: A multi-center phase-III trial of the German AGO Breast Study Group recruited 1284 pts from 12/98 until 4/03. Pts below 65 years of age were eligible if at least 4 axillary lymph nodes were infiltrated. In the experimental arm, pts were assigned to receive three courses each of epirubicin (150 mg/m 2 ), paclitaxel (225 mg/m 2 ) and cyclophosphamide (2500 mg/m 2 ) at 2-week intervals (q2w) (ETC) with G-CSF support (5µg/kg/SC day 3–10). In the standard arm 4 courses of conventional dosed epirubicin/cyclophosphamide (90/600 mg/m 2 ) followed by 4 courses of paclitaxel (175 mg/m 2 ) were given (EC→T). All cycles were administered in 3-week intervals without growth factor support. A second randomization ± epoetin alfa was performed in the IDD-ETC arm only (150IU/kg/sc three times weekly) to reduce the number of red blood cells (RBC9s) transfusion and to evaluate the impact of epoetin alfa on DFS and OS in the adjuvant setting. Results: 58% and 42% of the pts presented with 4–9 and ≥ 10 positive nodes with a median number of 8 involved nodes. The median age was 51 years and median follow-up was 122 months. We observed 604 DFS events (282 with IDD ETC; 322 with EC→T) (p = 0.00014, one-sided; HR 0.74; 95% CI, 0.63 to 0.87). IDD ETC improved DFS irrespective of nodal status, HER2 and ER status. 446 pts. have died (201 events in the IDD ETC arm vs. 245 events in the standard arm). 10 year OS rates were 69% with IDD ETC and 59% with EC→ T (p = 0.0007; two-sided; HR, 0.72; 95% CI, 0.60–0.87). Nine cases of acute myeloid leukemia or myelodysplastic syndrome occurred in the IDD ETC arm vs. two cases in the standard arm. 28% of pts in the IDD ETC arm vs. 13% in the IDD ETC arm plus epoetin alfa (p Conclusion: Intense dose-dense ETC remains significantly superior compared to standard chemotherapy after 10 years of follow-up. The risk of secondary leukemia/MDS in the IDD ETC arm (1.3% of pts) is comparable to that of the Cancadian CEF regimen. The prevention of RBC9s transfusions and anemia by the application of epoetin alfa in the IDD ETC-arm had no impact on DFS and OS. IDD ETC is a highly effective and safe regimen in the adjuvant treatment of high-risk breast cancer pts. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S3-4.