The role of ESR1 mutations in development of resistance to hormone therapy in patients with luminal subtypes of breast cancer
Summary. The hormone therapy has established itself as the basis for drug treatment of luminal types of breast cancer due to its high efficiency and low toxicity. However, some patients have a progression of the disease due to hormone preparations, that is explained by the development of resistance. Thus, the progression of the disease is expected in 50% of patients due to the first line of hormone therapy by tamoxifen and in a third part of patients with hormone preparations of the group of aromatase inhibitors. To understand the mechanisms of endocrine resistance, it is important to determine the primary or secondary (acquired) nature of it. In both cases, the resistance to hormone therapy may be due to a disruption in the balance between activator proteins and estrogen receptor (ER) suppressors and the stimulation of estrogen-independent signaling pathways of growth, and through mutations in the ESR1 gene which directly encodes ER expression. In the modern molecular oncology, the role of ESR1 mutations is actively discussed as an early and practically achievable (especially when repeat biopsies are impossible) marker for predicting the development of insensitivity to standard hormone regimens.
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