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Endocrine-resistant breast cancer: Underlying mechanisms and strategies for overcoming resistance

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Abstract

Estrogen plays important roles in the development and progression of breast cancer. However, onethird of breast cancers fail to respond to endocrine therapy and most endocrine-responsive breast cancers subsequently become resistant to endocrine therapy. A tremendous effort has been made to elucidate the mechanisms responsible for the development of endocrine-resistance in breast cancer. Since the main target molecule of estrogen in breast cancer is estrogen receptor (ER)-α, most studies have focused on investigating quantitative and qualitative changes in ER-α in endocrine-resistant breast cancer. Breast cancers expressing no ER-α fail to respond to endocrine therapy. Some breast cancers expressing ER-α also fail to respond to endocrine therapy and most breast cancers with acquired endocrine resistance retain ER-α expression, which suggests that the disappearance of ER-α in breast cancer cells is not a common cause of resistance to endocrine therapy. Recent molecular biological studies have shown evidence that qualitative and functional changes, such as gene mutations and phosphorylation of ER-α, cause endocrine resistance in breast cancer. In addition, it has been suggested that endocrine resistance could be induced by epigenetic changes, such as hypoxia, in breast cancer tissues. Understanding the precise mechanisms that underlie endocrine resistance may enable clinicians to develop new strategies for retarding or overcoming endocrine resistance in breast cancer.

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Abbreviations

ER:

Estrogen receptor

PgR:

Progesterone receptor

LH-RH:

Luteinizing hormone-releasing hormone

AP-1:

Activating protein1

EGF-R:

Epidermal growth factor receptor

PI3K:

Phosphatidylinositol-3-OH-kinase

HAT:

Histone acetyltransferase

ERBF1:

Estrogen receptor promoter B-associated factor 1

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  1. Department of Breast and Thyroid Surgery, Kawasaki Medical School, Japan

    Junichi Kurebayashi

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  1. Junichi Kurebayashi
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Reprint requests to Junichi Kurebayashi, Department of Breast and Thyroid Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan.

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Kurebayashi, J. Endocrine-resistant breast cancer: Underlying mechanisms and strategies for overcoming resistance. Breast Cancer 10, 112–119 (2003). https://doi.org/10.1007/BF02967635

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