Increased frequency of ESR1 mutation in metastatic breast cancer by dosing selective estrogen receptor modulator followed by aromatase inhibitor

Kaoru Takeshima, Tetsu Hayashida, Hinako Maeda, Ayako Nakashoji, Takamichi Yokoe, Tomoko Seki, Maiko Takahashi, Yuko Kitagawa

Research output: Contribution to journalArticlepeer-review

Abstract

In several recent studies on metastatic breast cancer (MBC), ligand binding domain mutations of the estrogen receptor, which is coded by the ESR1 gene, were induced by long-term endocrine therapy and resulted in acquired endocrine therapy resistance and poor outcomes. Knowledge of the association between the development of ESR1 mutation and the clinicopathologic features may guide the decision-making process of metastatic breast cancer treatment, including endocrine therapy. The aim of the present study was to evaluate the association between the development of ESR1 mutation and the clinicopathologic characteristics of patients with MBC. To evaluate the association between the development of ESR1 mutation and clinicopathologic features, a cohort of 22 patients with MBC were retrospectively analyzed using next generation sequencing. In 14 of 22 patients, four mutations were detected on the metastatic site, including Tyr537Ser, Glu542Asp, Leu536Arg and Arg548Cys. Univariate analysis demonstrated that the duration of aromatase inhibitor and selective estrogen receptor modulator treatment, as well as the age of treatment initiation for early-stage breast cancer, were significantly associated with the development of ESR1 mutation. ESR1 mutation was identified in all five patients who received selective estrogen receptor modulators in the adjuvant setting followed by aromatase inhibitors in the metastatic setting, as well as in two of the three patients who received no selective estrogen receptor modulators in adjuvant setting followed by aromatase inhibitors in the metastatic setting. In conclusion, the results of the present study suggested that administrating adjuvant selective estrogen receptor modulator followed by aromatase inhibitor for metastasis may increase the frequency of ESR1 mutation.

Original languageEnglish
Pages (from-to)1231-1238
Number of pages8
JournalOncology Letters
Volume20
Issue number2
DOIs
Publication statusPublished - 2020 Aug

Keywords

  • Aromatase inhibitor
  • ESR1 mutation
  • Endocrine therapy resistance
  • Metastatic breast cancer
  • Selective estrogen receptor modulator

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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