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

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

doi:10.3892/ol.2020.11669

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

Authors:
- Kaoru Takeshima
- Tetsu Hayashida
- Hinako Maeda
- Ayako Nakashoji
- Takamichi Yokoe
- Tomoko Seki
- Maiko Takahashi
- Yuko Kitagawa
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Affiliations: Department of Surgery, Saitama City Hospital, Saitama 336‑0911, Japan, Department of Surgery, Keio University School of Medicine, Tokyo 160‑8582, Japan
Published online on: May 22, 2020 https://doi.org/10.3892/ol.2020.11669
Pages: 1231-1238
Copyright: © Takeshima et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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