Plasma ESR1 mutations and outcome to first-line paclitaxel and bevacizumab in patients with advanced ER-positive/HER2-negative breast cancer

Bos, M.K.; Lam, S.W.; Motta, G.; Helmijr, J.C.A.; Beaufort, C.M.; Jonge, E. de; ... ; Sleijfer, S. (2023)

Article / Letter to editor

BackgroundESR1 mutations have been identified as mechanism for endocrine resistance and are also associated with a decreased overall survival. We assessed ESR1 mutations in circulating tumor DNA (ctDNA) for impact on outcome to taxane-based chemotherapy in advanced breast cancer patients.MethodsESR1 mutations 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 an ESR1 mutation detected and 85% (23/27) in wildtype ESR1 patients. In our exploratory analysis, median progression-free survival (PFS) was 8.2 months [95% CI, 7.6-8.8] for ESR1 mutant patients versus 8.7 months [95% confidence interval (CI), 8.3-9.2] for ESR1 wildtype patients [p = 0.47]. The median overall survival (OS) was 20.7 months [95% CI, 6.6-33.7] for ESR1 mutant patients versus 28.1 months [95% confidence interval (CI), 19.3-36.9] for ESR1 wildtype patients [p = 0.27]. Patients with >= two ESR1 mutations 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 between ESR1 and other mutations.ConclusionsPresence of ESR1 mutations in baseline ctDNA might not be associated with inferior PFS and OS in advanced breast cancer patients treated with paclitaxel/bevacizumab.

• HR plus
• HER2-advanced breast cancer
• ESR1 mutation
• Paclitaxel
• Bevacizumab
• ctDNA

• All authors: Bos, M.K.; Lam, S.W.; Motta, G.; Helmijr, J.C.A.; Beaufort, C.M.; Jonge, E. de; Martens, J.W.M.; E. boven; Jansen, M.P.H.M.; Jager, A.; Sleijfer, S.
• Date: 2023-05-25
• Journal: Breast Cancer Research and Treatment
• Volume: 200
• Issue: 2
• Pages: 271 - 279
• DOI: doi:10.1007/s10549-023-06965-5
• Link: https://link.springer.com/article/10.1007/s10549-023-06965-5