PLATELET GELATINASES AND SURVIVAL OF BREAST CANCER PATIENTS WITH OBESITY: THE RELATIONSHIP WITH MENOPAUSAL STATUS

Abstract

Summary. Obesity increases the risk of developing and worsens the course of some types of cancer, in particular breast cancer (BC). It is known about the paradoxical influence of obesity on the course of breast cancer associated with the menopausal status of patients. Aim: to investigate survival in connection with the levels of generation of superoxide radicals and activity of platelet gelatinases, the redox state of the tumor-adjacent adipose tissue (TAAT), the body mass index (BMI) and the menopausal status of patients with breast cancer. Object and methods: TAAT samples (post-operative material) and blood samples of 70 women with breast cancer were studied. EPR spectrometry, polyacrylamide gel zymography, general clinical and statistical methods were used. Results: in premenopausal patients, the rate of generation of superoxide radicals (SR) by platelets at normal weight and obesity does not differ, while in postmenopausal patients there is a significant difference between them (p<0.05) (by 1.4 times). An association between the levels of platelet and TAAT SR in postmenopausal patients was revealed. In premenopausal patients, the difference between the activity of platelet gelatinases in obesity and normal weight is unreliable (p>0.05), while in postmenopause there is a significant reliable difference (p<0.05) in the indicators of the total activity of MMP-2 and -9 according to normal weight and obesity (in 2.3 times). For postmenopausal patients, there is a high reliable association of activity indicators of platelet gelatinases and the speed of their SR generation. With platelet MMP-2 activity levels higher than 42 IU, patients had a significantly shorter life expectancy (p = 0.02) and a higher risk of adverse disease course (HR = 2.7) compared with lower enzyme activity levels. With platelet MMP-9 activity levels higher than 65 IU, patients had a significantly shorter life expectancy (p = 0.04) and a higher risk of adverse disease course (HR = 1.75) compared with lower enzyme activity levels. Conclusions: it is likely that in postmenopause, obesity is the most important prothrombogenic factor, which contributes to the survival of disseminated tumor cells (DTC) in the vascular bed and metastasis. This is due to the fact that estrogen metabolites additionally disturb the balance in the redox state of adipose tissue, thereby contributing to the deepening of systemic oxidative stress and thrombus formation. The obtained results indicate the prospect of finding and researching the factors that determine the paradoxical effect of obesity on the course of breast cancer, as promising prognostic markers for personalized approaches in anticancer therapy.