HORMONE RECEPTOR–DEPENDENT DIFFERENCES IN BLOOD REDOX STATE OF BREAST CANCER PATIENTS

In women of postmenopausal age, the level of circulating estrogen in blood serum and breast tissue is reduced, but the incidence of breast cancer in this female cohort remains high, indicating that there are other factors that contribute to the increase in morbidity. Aim: To investigate the level of Ceruloplasmin [CP], Transferrin [TF], NO-Hemoglobin [NO-Hb], Methemoglobin [MetHb], superoxide and NO-generating activity of neutrophils and Matrix Metalloproteinases-2 And -9 [MMP-2 and – 9] in the blood of patients with breast cancer in relation with the hormone receptor status of tumors. Object and Methods: We have studied the blood samples of patients of reproductive and postmenopausal age with breast cancer of stages II-IIІ. The levels of CP, TF, “free” iron, hemichromes, MetHb, NO-Hb, ubisemiquinone, superoxide and NOgenerating activity of neutrophils were investigated by the method of Electron Paramagnetic Resonance [EPR]. The level of active forms of gelatinases in blood serum was determined by zymography in a polyacrylamide gel. Results: In patients of reproductive and postmenopausal age with BC of ER+/PR+ and ER-/PR- status, the level of CP exceeded the corresponding index in healthy donors, and the level of TF was significantly lower than in control group. An increase in NO-Hb content in blood was observed, this index was the highest in patients of post-menopausal age with ER-/PR- status and directly correlated with NO-generating activity of neutrophils [r = 0.56; p <0.05]. The activity of MMP-9 in the serum of patients with ER-/PR- status was significantly higher [by 3.3 times] than in patients with ER+/PR+ status. In the blood of 78% of postmenopausal patients with breast cancer of ER-/PR- status, an increased content of estrogen metabolites - quinones and ubisemiquinones was found, the latter level was directly correlated with the stage of the tumor process (r = 0.58; p <0.05). It has been established that neutrophils in the blood of patients of reproductive age with ER+/PR+ and ER-/PR- breast cancer generate SOR with a rate 9 and 18 times higher than in donors, respectively, and NO generation rate was more than 12 times higher in both subgroups. Conclusion: We have detected the disturbed redox state of blood with the accumulation of compounds with hormonal and progenotoxic effects in patients with breast cancer, and such alterations depend on the hormone receptor status of tumors.