BackgroundESR1mutations have been identified as mechanism for endocrine resistance and are also associated with a decreased overall survival. We assessedESR1mutations in circulating tumor DNA (ctDNA) for impact on outcome to taxane-based chemotherapy in advanced breast cancer patients.MethodsESR1mutations were determined in archived plasma samples from patients treated with paclitaxel and bevacizumab (AT arm,N= 91) in the randomized phase II ATX study. Samples collected at baseline (n= 51) and at cycle 2 (n= 13, C2) were analyzed using a breast cancer next-generation sequencing panel. This study was powered to detect a benefit in progression-free survival (PFS) at six months for patients treated with paclitaxel/bevacizumab compared to historical trials with fulvestrant. PFS, overall survival (OS), and ctDNA dynamics were exploratory analyses.ResultsPFS at six months was 86% (18/21) in patients with anESR1mutation detected and 85% (23/27) in wildtypeESR1patients. In our exploratory analysis, median progression-free survival (PFS) was 8.2 months [95% CI, 7.6–8.8] forESR1mutant patients versus 8.7 months [95% confidence interval (CI), 8.3–9.2] forESR1wildtype patients [p= 0.47]. The median overall survival (OS) was 20.7 months [95% CI, 6.6–33.7] forESR1mutant patients versus 28.1 months [95% confidence interval (CI), 19.3–36.9] forESR1wildtype patients [p= 0.27]. Patients with ≥ twoESR1mutations had a significantly worse OS, but not PFS, compared to those who did not [p = 0.003]. Change in ctDNA level at C2 was not different betweenESR1and other mutations.ConclusionsPresence ofESR1mutations in baseline ctDNA might not be associated with inferior PFS and OS in advanced breast cancer patients treated with paclitaxel/bevacizumab.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10549-023-06965-5.