Experimental, Clinical and Morphological Analysis of H-Ras Oncoproteins for Locally Advanced Breast Cancer.

BACKGROUND: Activated forms of Ras are enhanced in both breast cancer as well as the cell lines with EGFR and HER2 expression. Therefore, H-Ras could be activated in breast tumours in the absence of direct mutational activation of Ras itself and could contribute to 20-50% of the cases. Expression inhibition, signal transduction interruption from H-Ras to the nucleus could become a promising therapeutic target. AIM: The aim of this study was to investigate the clinical and morphological criteria of locally advanced breast cancer and the expression of H-Ras oncoprotein in patients who have been subjected to different regimens of farnesyltransferase inhibitor. METHODS: H-Ras status was assessed by immunohistochemistry (IHC). RESULTS: An association between the expressions of H-Ras and Her2/neu (p = 0.001) as well as the tumour proliferation index Ki-67 (p = 0.001) in patients with breast cancer was established. Analysis of the relationship between H-Ras expression showed a relatively strong association with progression-free survival both before the treatment (V = 0.47; p = 0.001) and after the treatment (V = 0.45; p = 0.001). These results may indicate the clinical applicability of H-Ras as a prognostic factor or serve as a therapeutic target for breast cancer treatment. CONCLUSION: These results could indicate the potential clinical application of H-Ras as a prognostic factor or a therapeutic target for breast cancer treatment.

LONG-TERM RESULTS OF COMBINATION THERAPY FOR LOCALLY ADVANCED BREAST CANCER.

Breast cancer ranks first among the malignant tumors in women. In locally advanced breast cancer (LABC) treatment starts with neoadjuvant chemotherapy (CTx) with the standard regimens CMF, FAC, АС. A cytostatic drug, Arglabin, isolated and produced from Artemisia glabella Kar. et Kir., an endemic plant growing in Central Kazakhstan, has been under investigation in clinical trials. The research is aimed at investigating the long-term results of combination therapy of locally advanced breast cancer including different chemotherapy regimens and Arglabin as monotherapy. The present research includes 93 patients diagnosed with LABC aged from 35 to 75 years, including 60 patients with Stage 2, and 33 patients with Stage 3 breast cancer. All patients were split into 3 groups, two experimental and one control group. The control group consisted of 36 patients with LABC who underwent 4 cycles of neoadjuvant chemotherapy according to AC regimen (doxorubicine 50 mg/m2, cyclophosphamide 500 mg/m2). The experimental group 1 consisted of 30 patients who received 4 cycles of chemotherapy according to AC+Arglabin regimen (Arglabin 370 mg/m2 within 7 days), while experimental group 2 consisted of 27 patients who underwent 4 cycles of Arglabin as monotherapy. Actuarial calculations of the overall survival (OS) and disease-free survival (DFS) rates were done according to the Kaplan-Meier method, while the differences in indicators of control and experimental groups were estimated using the following methods: Cox's F-Test, χ2, Gehan's Wilcoxon Test. Overall one- and two-year survival in all groups of patients was 100%. Three-year survival rate in patients treated with chemotherapy according to AC regimen was (40,0±8,2)%, in patients combining AC chemotherapy with Arglabin it was (60,0±8,9)%. The lowest three-year survival rate (28,0±8,6)% was observed in patients treated with Arglabin as a monotherapy. The three-year survival rate in patients with breast cancer is statistically insignificant (χ2=4,407 at p=0,11042) between all groups; however, at the paired comparison by Gehan's Wilcoxon criterion a statistically significant difference has been observed between the group treated with Arglabin as monotherapy, and the group receiving chemotherapy according to AC+Arglabin regimen. The highest disease-free survival rates have been observed in the group of patients receiving chemotherapy according to AC+Arglabin regimen: 1-2-3-year survival rates are 100%, 100%, and 58%, respectively. In the group of patients who underwent chemotherapy according to AC regimen, 1-2-3-year disease-free survival rates are 92%, 92%, and 30%, respectively. Arglabin included in AC regimen positively increases a 3-year disease-free survival rate by 28% as compared to the standard regimen.