The work is based on the analysis and generalization of the results of the examination and treatment of 45 patients with the stage II-III of triple negative breast cancer (TNBC) who were diagnosed for the first time and received treatment at the clinic of the Department of Oncology of Shupyk National Healthcare University of Ukraine at the base of the Kyiv City Clinical Oncology Center.
The aim of this dissertation research was to improve the treatment outcomes of patients with triple-negative breast cancer in whom, at the initial diagnostic stage, immunohistochemical analysis of the tumor included the determination of topoisomerase II alpha (TOP IІα) expression as an additional marker to predict tumor response to chemotherapy. Specifically, the overexpression of TOP IІα (>46%) served as a predictor for a better response to anthracycline-containing chemotherapy regimens.
Depending on the level of TOP IІα expression in the primary tumor before the start of treatment, the patients who participated in the study were divided into two groups: with expression <45% and >46%. Accordingly, the first group included 21 patients with topoisomerase II alpha expression level <45%, and the second group included 17 patients with TOP IІα expression level >46%. The age
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of the patients ranged from 26 to 74 years (mean age 52.6±11.8 years). When distributing patients by age, the majority of patients in both groups fell into the age category of 51 to 69 years: in the group with
<45% TOP IIα expression there were 66.7% of patients, and in the group with >46% TOP IIα expression - 47.1%.
The formed groups were comparable in terms of age, gender, nature of the main pathology, level of TOP IІα expression, and overall condition.
This study aims to improve the treatment outcomes of patients with triple-negative breast cancer by individualizing therapeutic algorithms through the enhancement and supplementation of diagnostic measures, as well as refining treatment protocols. In pursuit of this objective, in this work there were employed standardized diagnostic algorithms and indications for prescribing neoadjuvant chemotherapy and its administration for patients with stage II-III TNBC.
During the recruitment of patients for this study, individuals who met the inclusion and exclusion criteria were considered for participation.
All patients underwent the standardized examination algorithm according to the standards: physical examination, laboratory blood and urine tests, ECG, mammography in 2 projections, X-ray of the chest in 2 projections, CT of the chest, abdomen, and pelvis with intravenous contrast, ultrasound of the abdominal organs, breast, and regional lymph nodes, trepan-biopsy of the tumor with morphological and immunohistochemical examination. If indicated, ultrasound of the pelvic organs and retroperitoneal space, computer tomography with intravenous contrast of the chest, abdomen, and pelvis, and radioisotope studies were conducted. The dimensions of the primary tumor and the dynamics on follow-up examinations were assessed using mammograms by measuring the maximum diameter of the tumor. Patients' age at the time of diagnosis, size, histological type, cell differentiation grade, immunohistochemical evaluation of estrogen receptors, progesterone receptors, HER2/neu, proliferative activity of tumor cells were determined. Based on this information, there was identified the molecular subtype of breast cancer, as well as the level of TOP IІα expression in tumor cells and the presence of metastases in regional lymph nodes.
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After diagnosing triple-negative breast cancer and conducting examinations according to standards, neoadjuvant chemotherapy (NACT) was prescribed to the patients.
Complete pathological response (CPR) of III-IV grades was achieved in 43.7% of patients with TOP IІα expression level <45%, compared to 47.4% among patients with TOP IІα expression level >46%.
Upon analysing the data, a correlation between CPR and a decrease in Ki67 levels was identified: in the group of patients who achieved CPR, an average decrease of -37.5% in Ki67 levels was observed (p=0.026), whereas, in the group where CPR was not achieved, an average decrease of -10.5% was noted.
When analysing the effectiveness of NACT regimens, the use of taxane-containing NACT was associated with a lower rate of failure to achieve CPR (p=0.015), HR = 0.002 (95% CI 0.000–0.290) compared to the use of non-taxane-containing NACT.
