Prognostic factors of metastatic luminal (Her2/neu-negative) breast cancer

Tarasenko T., Syvak L., Verevkina N., Лялькін С.А., Martynyuk O., Maydanevich N., Kasap N., Човган О.Є.

Summary. Types of breast cancer are classified based not only the size of tumor, spread to the lymph nodes or other organs of the body, but it is necessary to assess immunohistochemical (IHC) breast cancer types according to the expression of estrogen receptor (ER), progesterone receptor (PR), Ki-67 proliferative index, and human epidermal growth factor of receptor 2 (Her2). Approximately 75% of breast cancers are positive for estrogen receptor and, so they are termed the lumainal group. Hormone-sensitive breast cancer is determined by receptors able of perceiving the hormonal signal and translating it into the nucleus. The immunohistochemical status of recurrent tumor can differ from the primary biopsy. The search of noninvasive factors (including of polymorphic ESR1 (A-351G, T-397C) is relevant now for prognoses of hormone therapy in patients with metastatic luminal breast cancer. The aim of the study is to improve the effectiveness of hormone therapy with aromatase inhibitors in patients with metastatic luminal (Her2-negative) breast cancer based on the research of the ESR1 gene (A-351G, T-397C) polymorphic variants. The object and methods. Treatment results of 53 patients with metastatic luminal Her2/neu-negative breast cancer, who have been receiving the first-line of endocrine therapy with nonsteroidal aromatase inhibitor. The treatment response assessed every 12 weeks according to RECIST 1.1. In a year of treatment all patients were divided into 2 groups depending on the progression of the disease (І group is the progression up to 12 months and ІI group is the progression after 12 months). In case of progression disease, we provided molecular genetic testing of ESR1 in peripheral blood. ESR1 (A-351G, T-397C) polymorphism was detected by analysis of DNA restriction fragment length polymorphism in 1 intron of ESR1. The results of the study indicate the feasibility of determining mutations in the estrogen receptor gene (ESR1) in patients with metastatic luminal (Her2/neu-negative) breast cancer to predict the prognoses of the disease and the choice of personalized treatment. Conclusions. It has been established that the presence of polymorphic genotypes ESR1 A-351G (odds ratio (OR) 2.81 95% CI = 1.16–6.82, p=0,05) and ESR1 T-397C (OR 3.33 95% CI = 1,00–11.90, p=0,05) was associated with early disease progression in patients with metastatic luminal (Her2/neu-negative) breast cancer.

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