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Aromatase inhibitor (AI) combined with Gonadotropin-releasing hormone agonist (GnRH-a) have been recognized as an effective approach to adjuvant endocrinotherapy for breast cancer (BC) in premenopausal patients with adverse predictive factors. However, the risk of non-optimal suppression of the ovaries due to the mechanism of action of aromatase inhibitors has been proven. Recently published SOFT-EST studies showed that the blood estradiol (E2) level in 37% of patients was above the level that was permissible for the purpose of this group of drugs. And although today there is no enough scientific justification to interpret this result, the introduction of aromatase inhibitors in adjuvant therapy in young women requires the search for tactics to reduce the risk of mediated increase in estradiol against the background of such therapy. Alertness occurs when the E2 serum level exceeds the menopause limit by the time the aromatase inhibitors are prescribed. Objective of the study. Determine the tactics for minimizing the risk of increasing estradiol against the background of aromatase inhibitors in combination with GnRH-a in adjuvant therapy for breast cancer in premenopausal patients. Material and methods. 47 patients of ≤ 50 years old with GR + HER2- Stages I-III Breast Cancer and a regular menstrual cycle before the start of neo-/adjuvant chemotherapy were studied. E2 and FSH levels were assessed at the stage prior to chemotherapy and immediately prior to administering adjuvant endocrinotherapy. After the completion of chemotherapy, only 7 out of 47 women had the menstrual cycle - patients without clinical and biochemical suppression of ovarian function (SOF). 86% of cases had cytostatic amenorrhea (n = 40), of which 23 cases (58%) showed that this condition was not combined with the biochemical response of sex hormones, i.e. there was no biochemical SOF. Thus, the study group included 30 patients, who were supposed to be treated with aromatase inhibitors + GnRH analogues, and had no clinical or biochemical menopause by the time adjuvant endocrinotherapy was prescribed. In order to reduce the risk of mediated increase in estradiol, even with pharmaceutical “switching off” ovarian function, the patients were prescribed the GnRH analogue (Buserelin Depot) before starting aromatase inhibitors therapy. Results and conclusion. A progressive decrease in E2 level was determined after each subsequent administration of Buserelin Depot. The median values remained low only after the third injection. Following the chemotherapy, a decrease in estradiol was accompanied by a physiological increase in the FSH levels in 73% of women. The administration of Buserelin Depot led to a significant decrease in FSH median (p

The randomized clinical trials showed the effectiveness of the addition of ovarian suppression to tamoxifen or to aromatase inhibitors after adjuvant chemotherapy in women younger or older than 35 years, but with at least one high-risk factor for recurrence.However, the lack of clear criteria for evaluating the ovarian function after gonadotoxic chemotherapy, especially in women in the perimenopause, significantly complicates the choice of the right tactics for endocrine therapy. Despite proven efficacy of aromatase inhibitors as part of the adjuvant breast cancer therapy in women with preserved ovarian function in SOFT and TEXT trials, this tactic requires a more differentiated approach, according to many experts.The relative factors (STRAW criteria, age, gonadotoxicity of chemotherapy) for determining the probability of restoration of ovarian function after the chemotherapy were determined using the characteristics of the menstrual cycle in women with hormone-sensitive breast cancer based on the international trials available in the literature. The introduction of these methods for evaluating the ovarian function after chemotherapy in premenopausal women into the clinical guidelines for the adjuvant management of early breast cancer may make the choice of ovarian suppression more appropriate not only from the clinical, but also from the physiological point of view.