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Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Carcinogenesis of Triple-Negative Breast Cancer and Sex Steroid Hormones
Naoko Honma1, Yoko Matsuda2, Tetuo Mikami1
1Department of Pathology, Toho University Faculty of Medicine, Tokyo 143-8540, Japan.
Abstract:
Triple-negative breast cancer (TNBC) lacks an effective treatment target and is usually associated with a poor clinical outcome; however, hormone unresponsiveness, which is the most important biological characteristic of TNBC, only means the lack of nuclear estrogenic signaling through the classical estrogen receptor (ER), ER-α. Several sex steroid receptors other than ER-α: androgen receptor (AR), second ER, ER-β, and non-nuclear receptors represented by G-protein-coupled estrogen receptor (GPER), are frequently expressed in TNBC and their biological and clinical importance has been suggested by a large number of studies. Despite the structural similarity between each sex steroid hormone (androgens and estrogens) or each receptor (AR and ER-β), and similarity in the signaling mechanisms of these hormones, most studies or reviews focused on one of these receptors, and rarely reviewed them in a comprehensive way. Considering the coexistence of these hormones and their receptors in TNBC in a clinical setting, a comprehensive viewpoint would be important to correctly understand the association between the carcinogenic mechanism or pathobiology of TNBC and sex steroid hormones. In this review, the carcinogenic or pathobiological role of sex steroid hormones in TNBC is considered, focusing on the common and divergent features of the action of these hormones.
Insights
Triple-negative breast cancer (TNBC) is hormone-unresponsive via ER-α, but other sex steroid receptors like AR, ER-β, and GPER are present. This review comprehensively examines their roles in TNBC pathobiology.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) lacks targeted therapies and has poor outcomes.
- TNBC's hormone unresponsiveness is linked to the absence of classical estrogen receptor alpha (ER-α) signaling.
- Androgen receptor (AR), ER-beta (ER-β), and G-protein-coupled estrogen receptor (GPER) are frequently expressed in TNBC.
Purpose of the Study:
- To provide a comprehensive review of sex steroid hormones and their receptors in TNBC.
- To explore the common and divergent roles of these hormones in TNBC pathobiology.
- To understand the association between sex steroid signaling and TNBC carcinogenesis.
Main Methods:
- Literature review of studies on sex steroid receptors (AR, ER-β, GPER) in TNBC.
- Analysis of structural and signaling similarities/differences among these receptors.
- Synthesis of existing data on the clinical and biological importance of these receptors in TNBC.
Main Results:
- While ER-α is absent, AR, ER-β, and GPER are often expressed in TNBC.
- These receptors, despite structural similarities to ER-α, play distinct roles in TNBC.
- Evidence suggests significant biological and clinical relevance of these alternative sex steroid receptors in TNBC.
Conclusions:
- A comprehensive understanding of AR, ER-β, and GPER signaling is crucial for TNBC research.
- Targeting these alternative pathways may offer new therapeutic strategies for TNBC.
- Further research integrating the roles of multiple sex steroid hormones is needed for TNBC treatment.
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