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

M. K. Bos*, S. W. Lam, G. Motta, J. C.A. Helmijr, C. M. Beaufort, E. de Jonge, J. W.M. Martens, E. Boven, M. P.H.M. Jansen, A. Jager, S. Sleijfer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background: ESR1 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. Methods: ESR1 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. Results: PFS 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. Conclusions: Presence of ESR1 mutations in baseline ctDNA might not be associated with inferior PFS and OS in advanced breast cancer patients treated with paclitaxel/bevacizumab.

Original languageEnglish
Pages (from-to)271-279
Number of pages9
JournalBreast Cancer Research and Treatment
Volume200
Issue number2
Early online date25 May 2023
DOIs
Publication statusPublished - Jul 2023

Bibliographical note

Funding Information:
The ctDNA analysis of this study were funded by the Dutch Cancer Society (no. NKB-EMCR-2016-108154). The ATX trial was funded by F. Hofmann-la Roche Ltd (Woerden, the Netherlands).

Publisher Copyright:
© 2023, The Author(s).

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