Background. The role of neoadjuvant chemotherapy (NACT) in luminal HER2-negative breast cancer (BC) remains highly controversial due to the lack of reliable predictors of drug therapy efficacy.Objective: to evaluate the effectiveness of NACT in patients with aggressive luminal HER2-negative BC and to compare modern systems for assessing the pathomorphological response.Materials and methods. The tumor response to NACT regimens was assessed in 64 patients with aggressive luminal HER2-negative BC stage II–III. The median age of women was 46.5 years (range 31–76 years), 76.6 % had primary operable stages (cT1–3N0–1), locally advanced BC (cT4, cN2–3) – 23.4 % patients. The characteristics of BC were as follows: invasive ductal carcinoma (76.6 %), grade G₂ and G₃–54.7 % and 45.3 %, Ki-67 ranged from 20 % to 98 %, median 45 %. The ER expression level was low (1–10 %, ERlow) in 12.5 % and was more than 10 % in 87.5 % of cases. HER2 status corresponded to 0, 1+ and 2+ in the absence of gene amplification – in 50.0 %, 35.9 % and 14.1 % of patients, respectively. The rate of TILs <10 %, 10–20 % and >20 % was in 71.4 %, 10.7 % and 17.9 % of cases. After NACT with the inclusion of anthracyclines and taxanes ± platinum combinations (in BRCA mutated status), the patients underwent radical surgery (mastectomy or breast-conserving surgery) with an assessment of the pathological response.Results. 15.6 % of patients had a complete pathomorphological response (pCR) to treatment, which corresponded to the RCB-0 class and the pathomorphological stage ypT0N0. Residual tumor load with incomplete response was very significant – class RCB-I was noted in only 7.8 %, and RCB-II and RCB-III – in 39.1 % and 37.5 %, respectively. An increase in the size of the residual tumor and the number of affected lymph nodes were associated with an increase in the RCB class. Predictors of pCR achievement in luminal HER2-negative cancer were: grade G₃, rare histological forms of BC (medullary, metaplastic), rate of TILs ≥30 %, low ER expression, and HER2 0 status.Conclusion. Assessment of Ki-67, tumor grade, ER and HER2 rate, and TILs before starting NACT will help identify a group of high sensitivity to chemotherapy and optimize the treatment strategy in aggressive luminal HER2-negative BC.