Oestrogen receptor negativity in breast cancer: a cause or consequence?
Endocrine resistance, which occurs either by de novo or acquired route, is posing a major challenge in treating hormone-dependent breast cancers by endocrine therapies. The loss of oestrogen receptor α (ERα) expression is the vital cause of establishing endocrine resistance in this subtype. Understanding the mechanisms that determine the causes of this phenomenon are therefore essential to reduce the disease efficacy. But how we negate oestrogen receptor (ER) negativity and endocrine resistance in breast cancer is questionable. To answer that, two important approaches are considered: (1) understanding the cellular origin of heterogeneity and ER negativity in breast cancers and (2) characterization of molecular regulators of endocrine resistance. Breast tumours are heterogeneous in nature, having distinct molecular, cellular, histological and clinical behaviour. Recent advancements in perception of the heterogeneity of breast cancer revealed that the origin of a particular mammary tumour phenotype depends on the interactions between the cell of origin and driver genetic hits. On the other hand, histone deacetylases (HDACs), DNA methyltransferases (DNMTs), miRNAs and ubiquitin ligases emerged as vital molecular regulators of ER negativity in breast cancers. Restoring response to endocrine therapy through re-expression of ERα by modulating the expression of these molecular regulators is therefore considered as a relevant concept that can be implemented in treating ER-negative breast cancers. In this review, we will thoroughly discuss the underlying mechanisms for the loss of ERα expression and provide the future prospects for implementing the strategies to negate ER negativity in breast cancers.
['Gajulapalli|Vijaya Narasihma Reddy|VNR|', 'Malisetty|Vijaya Lakshmi|VL|', 'Chitta|Suresh Kumar|SK|', 'Manavathi|Bramanandam|B|']
D000818:Animals D018931:Antineoplastic Agents, Hormonal D001943:Breast Neoplasms D019175:DNA Methylation D019008:Drug Resistance, Neoplasm D004965:Estrogen Antagonists D047628:Estrogen Receptor alpha D005260:Female D015972:Gene Expression Regulation, Neoplastic D018740:Genetic Heterogeneity D006655:Histone Deacetylases D006801:Humans D051379:Mice D035683:MicroRNAs D009376:Neoplasms, Hormone-Dependent D064726:Triple Negative Breast Neoplasms D054875:Ubiquitination
endocrine resistance oestrogen receptor α ubiquitin ligases epigenetic factors microRNAs (miRNAs) oestrogen receptor (ER)-negative breast cancer