Background: Determining optimal adjuvant chemotherapy for early stage breast cancer depends on efficacy and toxicity.We sought to determine if T is equivalent to AC but with reduced toxicity.Methods: Pts with operable breast cancer with 0-3 positive nodes were enrolled on a 2x2 factorial design study which addressed(1)superiority of 6 vs.4 cycles of therapy(previously reported,Shulman,JCO 2012)and(2)equivalence of single-agent T to standard AC,defined as upper bound of 95%confidence interval(CI)of hazard ratio(HR)of T vs.AC,1.30 for the primary endpoint of relapse-free survival(RFS).A planned target of 567 RFS events required 4,646 pts with 4 yrs FU.At activation in 2002,T(80mg/m2)was q1wk for 12 or 18 wks and AC(60/600 mg/m2)was q3wk for 4 or 6 cycles.In 2003(570 pts enrolled)schedules were revised to 4 or 6 cycles q2wk for both T(175 mg/m2)and AC.The 6-cycle arms were dropped in 2008(3,171 pts enrolled)due to slow accrual.Relative effectiveness of T to AC is shown by hazard ratio(HR).Logrank p-values are measures of discordance but are not relevant for the equivalence question and are not adjusted for multiple comparisons.Results: After enrolling 3,871 pts,the study closed in 2010 due to slowing accrual.With a median follow-up of 6.1 yrs there are 437 RFS events.The HR of 1.26(95%CI: 1.05-1.53; p 5 0.02)does not allow a conclusion of equivalence of T with AC.With 266 deaths the HR for overall survival(OS)is 1.27(95%CI51.00-1.62; p 5 0.05),favoring AC.The estimated absolute advantage of AC at 5 yrs is 3%(91 vs.88%)for RFS and 1%(95 vs.94%)for OS.All 9 treatment-related deaths were in pts receiving AC and are included in the survival analysis.The incidence of Grade 31 toxicity for AC vs T was 33%vs.4%for hematologic toxicity and 36%vs 22%for non-hematologic toxicity.Conclusions: This trial did not show equivalence of T to AC,a conclusion that is very unlikely to change with additional follow-up.T was less toxic than AC.