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Background: Dose-dense sequential chemotherapy with anthracyclines and taxanes achieved an 18% reduction of recurrence risk in early breast cancer (BC). The optimal chemotherapy schedule and interval between cycles remain under investigation., Methods: Overall, 990 patients were randomised to receive either three cycles of epirubicin (E, 110 mg/m 2 ) every 2 weeks followed by 3 cycles of paclitaxel (T, 200 mg/m 2 ) every 2 weeks followed by three cycles of intensified CMF (Control Arm A, E-T-CMF) that was previously used in BC or three cycles of epirubicin followed by three cycles of CMF followed by nine consecutive weekly cycles of docetaxel (wD) 35 mg/m 2 (Arm B, E-CMF-wD) or nine consecutive weekly cycles of paclitaxel (wT) 80 mg/m 2 (Arm C, E-CMF-wT). Trastuzumab was administered for HER2-positive disease., Results: At a median follow-up of 13.3 years, 330 disease-free survival (DFS) events (33.3%) were reported. DFS and overall survival (OS) did not differ between patients in the combined B and C arms versus arm A either in the entire cohort (HR = 0.90, P = 0.38 and HR = 0.85, P = 0.20) or among trastuzumab-treated patients (HR = 0.69, P = 0.13 and HR = 0.67, P = 0.13). Thirty-four patients (3.4%) developed secondary neoplasms., Conclusions: Overall, no significant differences in survival were found amongst the studied regimens after a long-term observational period., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12610000151033., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)