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

Abstract

BACKGROUND: Activated forms of RAS increase both in breast cancer and in cell lines in the presence of estimated glomerular filtration rate (EGFR) or HER2 expression. HRAS oncoproteins play an important role in enhancing the proliferation and resistance of breast cancer tumor cells to apoptosis. A number of studies have shown a significant decrease in EGFR expression after neoadjuvant chemotherapy, which has been clinical, manifested by an improvement in immediate efficacy and an increase in overall and relapse-free breast cancer survival rates.
 AIM: The aim of the study was to study relapse-free survival depending on the expression of the H-RAS oncoprotein in patients with breast cancer who received different treatment regimens for the farnesyltransferase inhibitor.
 METHODS: H-RAS status was assessed by immunohistochemistry.
 RESULTS: A comparative analysis of patients with negative expression of H-RAS oncoproteins showed a statistically significant increase in relapse-free survival in the subgroups who received neoadjuvant chemotherapy according to the AC regimen (adriablastin + cyclophosphamide) and AC + arglabin, compared with monotherapy by arglabin: Kruskal–Wallis= 12.56, where p = 0.001. A comparative analysis of patients with positive expression of H-RAS showed that in the subgroups treated with arglabin and AC+arglabin, there was a statistically significant increase in relapse-free survival compared with the AC subgroup: Kruskal–Wallis = 10.96, where p = 0.004. It was established that the positive expression of H-RAS negatively affects not only the direct effectiveness of neoadjuvant therapy but also worsens the rates of relapse-free survival. However, in patients with positive H-RAS expression who received arglabin in monotherapy, there was a statistically significant increase in relapse-free survival up to 16.5 ± 1.1 months compared with the standard AC regimen (13.5 ± 1.1 months) (р ˂ 0.05), the addition of arglabin to the standard AC regime also increased this indicator to 16.4 ± 1.2 months (р ˂ 0.05).
 CONCLUSION: These results may indicate the clinical applicability of determining H-RAS as a prognostic factor for relapse-free survival in breast cancer.