Znachenie molekulyarnykh markerov pri vybore neoad\"yuvantnoy khimioterapii mestno-rasprostranennogo raka molochnoy zhelezy


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Abstract

The randomized study «The role of taxanes in combination with anthracyclines (TAC) and without anthracyclines (TC) in the neoadjuvant treatment of patients with locally advanced breast cancer (BC)» (2010 to 2013) was performed; 120 patients were randomized in a ratio of 1:1 to receive chemotherapy according to the TAC or TC schemes. Patients with operable breast cancer forms, in accordance with the randomization in the first group, have received 4 to 8 (average 4,6) cycles of chemotherapy TAC scheme (docetaxel 75 mg/m 2, doxorubicin 60 mg/m 2, cyclophosphamide 600 mg/m 2) once a 3 weeks; second group of patients - 4 to 8 (mean 4,9) cycles of chemotherapy TC scheme (docetaxel 75 mg/m 2, cyclophosphamide 600 mg/m 2) once a 3 weeks against the background of standard pre- and postmedikation using dexamethasone. The treatment groups have shown a significant difference between the rate of objective clinical response (89.8 vs. 74.5 %; p < 0,05) and indicators of pathomorphological complete response (22.0 vs. 10.6 %, p < 0.05 ), respectively. Patients with HER2 + breast cancer have received targeted therapy with trastuzumab at standard doses in addition to the polychemotherapy. In different biological subtypes of breast cancer, significant differences in the rates of pathomorphological complete response of the tumor and regional lymph nodes (pCR) after neoadjuvant taxane - containing chemotherapy ( TAC and TC schemes) were revealed. In luminal subtype A. pCR rate was 7.3 %, luminal B - 16.7 %, triplenegative - 24 %, HER2 + breast cancer - 27.3 % (p < 0.05). BRCA1 mutation was found in 9 % of patients: triple-negative breast cancer was diagnosed in 5 (55%) patients with mutation in the gene BRCA1 5382insC, and luminal A subtype of breast cancer - 4 (45 %) patients. The high efficiency of TAC and TC schemes in patients with BRCA 1 - associated breast cancer was determined: overall objective response rate (complete + partial regression) was observed in 8 (88.9 %) patients, pathomorphological complete response (pCR) - in 4 (44.4 %) patients. Low level of в-tubulin III type breast cancer gene expression is reliable predictive factor for pathomorphological complete response (pCR) to taxane-containing chemotherapy in 23.8 % of patients vs 12.5 and 15.4 % with an average and high expression of markers (p < 0,05). High and medium level of TOR2a gene expression increases by 2.6 and 2.8 times the frequency of significant drug pathomorphism (4 + 5 stages by Miller-Payne) compared with its low level (p <0,05), which allows to consider TOR2a as a predictive marker of sensitivity to anthracycline antibiotics.

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