The role of ESR1 gene mutation in therapy selection for HR+/HER2- metastatic breast cancer: A review

Estrogen receptors are detected in more than 70% of cases of metastatic breast cancer (mBC). Currently, various hormonal therapy options are used to treat these tumors. However, modern oncology faces an acute problem of acquired resistance to hormonal therapy, including late lines of therapy for HR-positive (HR+) and HER2-negative (HER2-) mBC. The common causes of resistance include mutations in the ESR1 gene that are usually absent in the primary tumor. These mutations are associated with aggravation of the disease. Until recently, their detection was only of prognostic value and was not taken into account when choosing the treatment regimen. As the new data become available on the role of mutations in the ESR1 gene and their possible impact on the choice of mBC therapy, it seems appropriate to consider the main criteria for testing and test methods to detect the mutations in routine clinical practice. This review article addresses issues related to optimal treatment for progression of HR+/HER2- mBC during endocrine therapy, taking into account the accumulated data on mutations in the ESR1 gene. We also consider the available data on the studied oral selective estrogen receptor destructors as drugs that significantly increase survival in late lines of therapy for hormone-dependent tumors.