The relevance of the work is due to the need for additional research to better understand the prevalence of ESR1 mutations at different stages of recurrent disease and their prognostic implications. The purpose of the study was to determine the incidence of ESR1 mutations in ER-positive breast cancer, its prognostic value in the choice of treatment. Materials and methods. A systematic review of quality studies, which were taken from PubMed and Thomas Reuters Web of Science databases, published between 2007 and 2019 was performed. Search terms included ESR1 mutations, estrogen receptor, breast cancer, recurrence, metastasis, aromatase inhibitors, fulvestrant and tamoxifen. Only full-text studies in English on the development of ESR1 mutations and their outcomes on disease progression were included. Studies were selected using predefined data fields, taking into account the quality of the study. This prospective clinical study is conducted by means of molecular genetic analysis, namely, gene polymorphism analysis by polymerase chain reaction. This study is carried out on the basis of the Kyiv City Clinical Oncology Center and the Department of Oncology of the Bogomolets National Medical University. A retrospective cohort of hormone receptor positive breast cancer patients experiencing either local or metastatic recurrence was collected from available archival specimens. All clinical data were obtained from the patients' clinical records by an expert breast oncologist. This included age, TNM stage, grade, immunohistochemistry scores for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and treatment lines. Results and discussion. Estrogen receptor and progesterone receptor positivity was determined based on local pathology practice (> 1% positively stained cells). The article demonstrated that ESR1 mutations often occur during AI therapy in the setting of metastasis and may play a role in metastasis progression. Advances in DNA sequencing technology have led to more sensitive detection of ESR1 mutations in clinical samples, and there are now several studies using sequencing and ddPCR techniques to track ESR1 and other mutations during treatment and progression. Targeted DNA sequencing and ddPCR technologies have shown that ESR1 mutations may pre-exist in approximately 5% of primary tumors and are significantly enriched by 30-40% in the setting of metastasis. The ctDNA analysis provides a simple, non-invasive and relatively inexpensive method for monitoring mutations that may arise during treatment, which can ultimately be used to guide treatment decisions. Conclusion. Importantly, ESR1 mutation monitoring alone is not clinically predictive of treatment; however, monitoring the acquisition of stem cell or other mutations may predict response and/or progression of treated cancers. Currently, patients with tumors expressing ESR1 mutations are best treated with the combination of fulvestrant and palbociclib, as this combination has significantly improved PFS in patients with most identified ESR1 mutations. Ongoing clinical trials using fulvestrant with specific PI3K-alpha inhibitors are showing promising clinical results, but analysis of whether patients with specific ESR1 mutations will benefit from this treatment has not yet been published
Keywords: ESR1-mutations, DNA sequencing, estrogen receptors, progesterone receptors, hormone-dependent neoplasms
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