Changes in systemic oxidative stress correlate to chemoresistance and poor prognosis features in women with breast cancer

Abstract

ObjectivesBreast cancer is a malignant neoplasm that affects women worldwide, and cytotoxic chemotherapy remains a primary treatment modality. In breast cancer, many women experience therapeutic failure and unfavorable clinical outcomes due to mechanisms related to chemoresistance acquisition, which may include oxidative stress. In this study, we investigated the systemic oxidative stress profile of women diagnosed with chemoresistant breast cancer and evaluated the correlation of this profile with clinicopathological features. MethodsThe oxidative stress levels were determined based on lipid peroxidation and nitric oxide metabolite (NOx) measurements. Chemoresistance was determined based on the Response Evaluation Criteria in Solid Tumors guidelines, and patients were categorized as responsive (complete response) or chemoresistant (partial or no response). ResultsReduced lipid peroxide levels were observed independent of the pattern of chemotherapy response, without NOx variation. The type of drug schedule did not interfere with oxidative stress levels in the responsive patients. However, lipid peroxide levels were reduced in patients in the chemoresistant group receiving the combination of adryamicin+ciclofosfamide+Taxol. Additionally, lipid peroxidation strongly correlated with high histological grade and obesity in chemoresistant patients, while NOx correlated with disease stage, risk of death and recurrence, and menopausal status. ConclusionThese findings highlight lipid peroxidation and NOx concentrations as putative markers of chemotherapy response in human breast cancer patients.