THE ROLE OF CYTOCHROME P450 ISOFORMS IN THE BREAST CANCER COURSE DEPENDING ON THE TUMOR MOLECULAR SUBTYPE

Aim: to investigate the levels of cytochrome P450 and its CYP 1A2, CYP 1B1 isoforms in tumor tissue and mammary adipose tissue in normal weight and overweight patients with different subtypes of breast cancer (BC). Object and methods: The surgical tissue of 73 patients with stage II (n=40) and III (n=33) BC aged 48.2 ± 10.2 years was used in the study. Luminal A breast cancer (LABC) was diagnosed in 35 patients; 38 patients had triple-negative BC (TNBC). The level of cytochrome P450 and its CYP 1A2, CYP 1B1 and CYP 19A1 isoforms in the tumor tissue and mammary adipose tissue was examined by electron paramagnetic resonance and spectrophotometrically. Enzymatic formation of estrogen adducts was determined by gas-liquid chromatography. Statistical analysis was performed using the R project (www.r-project.org). Results: The diverse levels of cytochrome P450 isoforms were determined in BC of different molecular subtypes. The levels of CYP 19A1 і CYP 1B1 isoforms in the tumor tissue of patients with TNBC were 1.8 times higher as compared to the patients with LABC. Increase in CYP19A1 level was especially evident in TNBC patient aged ≥50 years and body mass index (BMI) of ≥25 kg/m². Relation between CYP 1A2 levels was the opposite. The rate of superoxide radicals’ production in both tumor tissue and tumor bordering adipose tissue was higher in TNBC patients. The correlation between high CYP 1B1 level together with the low level of CYP 1A2 and worse 5 years relapse-free survival in both TNBC and LABC patients was revealed. There was demonstrated a relation between increased urinary level of marker of oxidative DNA damage (8-OHdG) and overall survival of patients with BC. Conclusions: the spectrum and degree of changes in the levels of P-450 isoforms depend on the BC molecular subtype: levels of CYP 19A1 and CYP 1B1 are much higher, and level of CYP 1A2 is significantly lower in patients with TNBC compared to LABC patients. The level of cytochromes CYP 1A2 and CYP 1B1, patients’ body mass index and the duration of estrogen exposure can serve as possible predictors of unfavorable TNBC and LABC course.