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Int. J. Mol. Sci. 2013, 14(1), 108-145; doi:10.3390/ijms14010108

Mechanisms of Resistance to Endocrine Therapy in Breast Cancer: Focus on Signaling Pathways, miRNAs and Genetically Based Resistance

1,†, 1,2,†
1 Department of Reproductive Biology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Vasco de Quiroga No. 15, Tlalpan, México 14000, D.F., Mexico 2 Department of Pharmacology, Center for Research and Advanced Studies, Avenida Instituto Politécnico Nacional 2508, México 07360, D.F., Mexico These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 15 October 2012 / Revised: 10 December 2012 / Accepted: 12 December 2012 / Published: 20 December 2012
(This article belongs to the Special Issue Advances in Molecular Oncology (special issue))
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Breast cancer is the most frequent malignancy diagnosed in women. Approximately 70% of breast tumors express the estrogen receptor (ER). Tamoxifen and aromatase inhibitors (AIs) are the most common and effective therapies for patients with ERα-positive breast cancer. Alone or combined with chemotherapy, tamoxifen significantly reduces disease progression and is associated with more favorable impact on survival in patients. Unfortunately, endocrine resistance occurs, either de novo or acquired during the course of the treatment. The mechanisms that contribute to hormonal resistance include loss or modification in the ERα expression, regulation of signal transduction pathways, altered expression of specific microRNAs, balance of co-regulatory proteins, and genetic polymorphisms involved in tamoxifen metabolic activity. Because of the clinical consequences of endocrine resistance, new treatment strategies are arising to make the cells sensitive to tamoxifen. Here, we will review the current knowledge on mechanisms of endocrine resistance in breast cancer cells. In addition, we will discuss novel therapeutic strategies to overcome such resistance. Undoubtedly, circumventing endocrine resistance should help to improve therapy for the benefit of breast cancer patients.
Keywords: endocrine therapy; breast cancer; estrogen receptor; hormonal resistance endocrine therapy; breast cancer; estrogen receptor; hormonal resistance
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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García-Becerra, R.; Santos, N.; Díaz, L.; Camacho, J. Mechanisms of Resistance to Endocrine Therapy in Breast Cancer: Focus on Signaling Pathways, miRNAs and Genetically Based Resistance. Int. J. Mol. Sci. 2013, 14, 108-145.

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