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Mechanisms of hormonal therapy resistance in breast cancer

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Abstract

Whilst estrogen receptor (ER)-positive breast cancers are preferentially treated with hormone therapy, approximately one-third of them relapse. The mechanisms of refractoriness have been investigated by numerous studies but have not been fully clarified. Hormonal therapy resistance, particularly aromatase inhibitor (AI) resistance, may be related to the acquisition of alternative intracellular ER signaling. We have been investing the mechanisms using cancer specimens and cell lines by monitoring the transcription activity of ERs. AI refractory specimens showed diverse ER activity in the adenovirus estrogen receptor element-green fluorescent protein (ERE-GFP) assay and varied sensitivity to anti-estrogens, indicating the existence of multiple resistant mechanisms. We established six different types of cell lines mimicking AI resistance from ERE-GFP-introduced ER-positive cell lines. They revealed that multiple and alternative ER activating pathways were involved in the resistance, such as phosphorylation-dependent or androgen metabolite-dependent mechanisms. The response to fulvestrant and mammalian target of rapamycin inhibitor also varied among individual resistant cell lines. These results indicate that further subclassification of ER-positive breast cancer is extremely important to decide the therapeutic management of not only hormonal therapy but also new molecular target therapy.

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Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Molecular and Functional Dynamics, and Center for Regulatory Epigenomics and Diseases, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan

    Shin-ichi Hayashi & Mariko Kimura

  2. Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan

    Mariko Kimura

Authors
  1. Shin-ichi Hayashi
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  2. Mariko Kimura
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Correspondence to Shin-ichi Hayashi.

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Hayashi, Si., Kimura, M. Mechanisms of hormonal therapy resistance in breast cancer. Int J Clin Oncol 20, 262–267 (2015). https://doi.org/10.1007/s10147-015-0788-5

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  • DOI: https://doi.org/10.1007/s10147-015-0788-5

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