Research Topic

Hormone Receptors and Breast Cancer

About this Research Topic

Breast cancer is the most commonly diagnosed cancer in women worldwide and is the second leading cause of cancer-related deaths. The vast majority of breast cancers arise from epithelial cells, either in the ducts or lobules, as a consequence of genetic and epigenetic alterations, which lead to aberrant growth control and disruption of intracellular signalling at the tissue level. For these reasons, breast cancer is a heterogeneous disease with multiple sub-types, with distinct cells of origin and etiology.

The increased expression of estrogen receptors (ER), that occurs at the earlier stages of breast tumor development and is common to different genetic lesions, has a wide impact, since about 75% of breast cancers expresses ER. ER are transcription factors that, upon binding to the steroid hormone estrogen, migrate in the nucleus and drive specific gene expression programs that intercept growth control pathways. Therefore, inhibiting ER function, in particular ERalpha, is the goal of endocrine therapy through the use of hormone-based therapeutics such as tamoxifen, fulvestrant and aromatase inhibitors. The application of these drugs as adjuvant therapies has led to a significant reduction in mortality; however, intrinsic and acquired resistance inevitably emerges. ER mutations or loss of expression, alteration in ER coactivators and corepressors, overexpression and/or amplification of growth factor receptors that impinge on the PI3K/AKT/mTOR and RAF/MEK/ERK pathways and alterations of cell-cycle checkpoints are the main molecular mechanisms responsible of the resistance to endocrine therapy. In the last years, our understanding of the mechanisms underlying hormone-therapy resistance has improved and this has led to the approval of three agents: the mTOR inhibitor everolimus, and two CDK 4/6 inhibitors, palbociclib and ribociclib. However, despite these successful strategies, more targets need to be identified, together with reliable and reproducible biomarkers to monitor the evolution of the disease since cancer genome is dynamic over time.

In addition to the problem of intrinsic and acquired hormone resistance, there is a consistent number of breast tumors that do not express ER. Breast cancers lacking ERalpha, progesterone receptor, and the overexpression of epidermal growth factor receptor 2 (HER2), constitute the so-called triple-negative breast cancers (TNBCs). TNBCs constitute about 10-30% of all breast cancers and are associated with younger age and higher stage at diagnosis, higher nuclear grade and mitotic activity, and poorer prognosis. They are a group with heterogeneous characteristics and represent a challenge for therapy.

On the other hand, other steroid receptors, such as vitamin D receptor, glucocorticoid and androgen receptors, as well as tyrosine kinase receptors, including IGF-1 and insulin receptors, can be also expressed in breast cells, and their role and/or the cooperative nature of their activity might deserve further studies.

This Research Topic aims to gather up-to-date and novel point of views in the field of hormone receptors and breast cancers. Potential contributions may include, but are not limited to the description of the molecular circuits regulated by hormone receptors in breast cancer, TNBC and its related aspects, intrinsic and acquired hormone resistance, as well as new therapeutic targets in this field.


Keywords: Estrogen receptor, Steroid receptors, Tyrosine kinase receptors, Hormone resistance, Triple negative breast cancer


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Breast cancer is the most commonly diagnosed cancer in women worldwide and is the second leading cause of cancer-related deaths. The vast majority of breast cancers arise from epithelial cells, either in the ducts or lobules, as a consequence of genetic and epigenetic alterations, which lead to aberrant growth control and disruption of intracellular signalling at the tissue level. For these reasons, breast cancer is a heterogeneous disease with multiple sub-types, with distinct cells of origin and etiology.

The increased expression of estrogen receptors (ER), that occurs at the earlier stages of breast tumor development and is common to different genetic lesions, has a wide impact, since about 75% of breast cancers expresses ER. ER are transcription factors that, upon binding to the steroid hormone estrogen, migrate in the nucleus and drive specific gene expression programs that intercept growth control pathways. Therefore, inhibiting ER function, in particular ERalpha, is the goal of endocrine therapy through the use of hormone-based therapeutics such as tamoxifen, fulvestrant and aromatase inhibitors. The application of these drugs as adjuvant therapies has led to a significant reduction in mortality; however, intrinsic and acquired resistance inevitably emerges. ER mutations or loss of expression, alteration in ER coactivators and corepressors, overexpression and/or amplification of growth factor receptors that impinge on the PI3K/AKT/mTOR and RAF/MEK/ERK pathways and alterations of cell-cycle checkpoints are the main molecular mechanisms responsible of the resistance to endocrine therapy. In the last years, our understanding of the mechanisms underlying hormone-therapy resistance has improved and this has led to the approval of three agents: the mTOR inhibitor everolimus, and two CDK 4/6 inhibitors, palbociclib and ribociclib. However, despite these successful strategies, more targets need to be identified, together with reliable and reproducible biomarkers to monitor the evolution of the disease since cancer genome is dynamic over time.

In addition to the problem of intrinsic and acquired hormone resistance, there is a consistent number of breast tumors that do not express ER. Breast cancers lacking ERalpha, progesterone receptor, and the overexpression of epidermal growth factor receptor 2 (HER2), constitute the so-called triple-negative breast cancers (TNBCs). TNBCs constitute about 10-30% of all breast cancers and are associated with younger age and higher stage at diagnosis, higher nuclear grade and mitotic activity, and poorer prognosis. They are a group with heterogeneous characteristics and represent a challenge for therapy.

On the other hand, other steroid receptors, such as vitamin D receptor, glucocorticoid and androgen receptors, as well as tyrosine kinase receptors, including IGF-1 and insulin receptors, can be also expressed in breast cells, and their role and/or the cooperative nature of their activity might deserve further studies.

This Research Topic aims to gather up-to-date and novel point of views in the field of hormone receptors and breast cancers. Potential contributions may include, but are not limited to the description of the molecular circuits regulated by hormone receptors in breast cancer, TNBC and its related aspects, intrinsic and acquired hormone resistance, as well as new therapeutic targets in this field.


Keywords: Estrogen receptor, Steroid receptors, Tyrosine kinase receptors, Hormone resistance, Triple negative breast cancer


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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31 January 2018 Manuscript

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Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

31 January 2018 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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