Resistance to endocrine therapy in breast cancer: molecular mechanisms and future goals

• Published in: Breast cancer research and treatment 2019-02, Vol.173 (3), p.489-497
• Main Authors: Szostakowska, Małgorzata, Trębińska-Stryjewska, Alicja, Grzybowska, Ewa Anna, Fabisiewicz, Anna
• Format: Article
• Language: English
• Subjects: Antiestrogens; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - adverse effects; Antineoplastic Agents, Hormonal - therapeutic use; Autophagy - drug effects; Biomarkers, Tumor; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - etiology; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer patients; Cancer research; Cancer treatment; Care and treatment; Cell survival; Drug Resistance, Neoplasm; Endocrine therapy; Estrogen receptors; Estrogens; Female; Genes; Genetic aspects; Health aspects; Humans; Medicine; Medicine & Public Health; Molecular modelling; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Oncology; Patients; Phenols (Class of compounds); Receptors, Estrogen - antagonists & inhibitors; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; Recurrence (Disease); Review; Transcription (Genetics); Tumors; Unfolded Protein Response - drug effects
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-018-5023-4

Introduction The majority of breast cancers (BCs) are characterized by the expression of estrogen receptor alpha (ERα+). ERα acts as ligand-dependent transcription factor for genes associated with cell survival, proliferation, and tumor growth. Thus, blocking the estrogen agonist effect on ERα is the main strategy in the treatment of ERα+ BCs. However, despite the development of targeted anti-estrogen therapies for ER+ BC, around 30–50% of early breast cancer patients will relapse. Acquired resistance to endocrine therapy is a great challenge in ER+ BC patient treatment. Discussion Anti-estrogen resistance is a consequence of molecular changes, which allow for tumor growth irrespective of estrogen presence. Those changes may be associated with ERα modifications either at the genetic, regulatory or protein level. Additionally, the activation of alternate growth pathways and/or cell survival mechanisms can lead to estrogen-independence and endocrine resistance. Conclusion This comprehensive review summarizes molecular mechanisms associated with resistance to anti-estrogen therapy, focusing on genetic alterations, stress responses, cell survival mechanisms, and cell reprogramming.