Parâmetros de saúde metabólica e visual em pacientes diagnosticadas com câncer de mama em tratamento anticâncer

Abstract

Female breast cancer, according to current estimates, is still reaching a very high level of incidence and prevalence in Brazil and Pará. The need for studies that expand knowledge about therapeutic options and mitigate the damage suffered by cancer becomes innovative in our region. Thus, we aim to determine and assess metabolic and visual health parameters in patients diagnosed with breast cancer exposed to anti-cancer therapies. The specific objectives were divided into three sections: Section I: determine lipid, anthropometric, oxidative stress and pro-inflammatory cytokine markers to assess metabolic health; Section II: determine tamoxifen metabolites (4-hydroxy tamoxifen and endoxifen) and correlate with blood lipids to assess drug interaction and metabolism with lipids; Section III: Perform visual tests to assess the effect of anticancer therapies on retinal thickness. Research approved by the ethics committee with opinion number 1.915.051 (CEP-HOL) and 1.897.057 (CEP-ICS-UFPA) from March 2017 to September 2019. It consisted of 40 women diagnosed with breast cancer (Ductal Carcinoma Grade II and III) in a public cancer reference hospital in Belém of Pará and who consented to participate in the research. A group of 20 patients formed the chemotherapy group (GQt), 20 patients the tamoxifen hormone therapy group (GTam) and another group of women without cancer was constituted as a comparative control (GC) based on the inclusion criteria. For the determination of biochemical markers, the automated method was used; anthropometry followed the Ministry of Health manual; for oxidative stress the colorimetric method; for the measurement of cytokines the ELISA method; for the determination of tamoxifen and metabolites in plasma, High Performance Liquid Chromatography (HPLC) was used; for retinal analyses, optical coherence tomography (OCT) was used. The results obtained showed that the patients were predominantly women aged between 40 and 50 years, brown, with an income of 1 to 3 minimum wages, were in pre- and post-menopause; were overweight/obese with high BMI, between 25 to 29.9 kg/m2, waist circumference above 80 cm and did not perform regular physical activity; the mean levels of lipids were altered in both groups studied, but with emphasis on the chemotherapy group with elevation of total cholesterol, LDL and triglycerides and low levels of HDL cholesterol, (p<0.05); the antioxidant parameters (TEAC, GSH, CAT and SOD) showed low levels of GSH and high CAT activity for the chemotherapy group and less activity for the tamoxifen group compared to the control (p<0.01); the pro-oxidant parameters (MDA and NO) showed that chemotherapy patients had a higher level of lipid peroxidation than tamoxifen patients compared to control (p<0.05); the GSH/MDA ratio showed greater sensitivity to oxidative damage for chemotherapy patients (p<0.01); as for cytokines, TNF-α and IL-6, they were elevated both in the chemotherapy group and in the tamoxifen group (p<0.05). Mean plasma concentrations of tamoxifen, 4-hydroxy tamoxifen, and endoxifen were 62 ng/mL, 1.04 ng/mL and 8.79 ng/mL; triglyceride levels ranged from 59 to 352 mg/dL, total cholesterol from 157 to 321 mg/dL, LDL-c from 72 mg/dL to 176 mg/dL and HDL-c from 25.1 mg/dL to 62.8 mg/dL; there was no significant association between tamoxifen and metabolites with cholesterol and triglyceride levels; there was a weak association between tamoxifen and its active metabolites with HDLc, LDLc and VLDLc. Mean retinal macular thickness revealed no significant difference between patients who received chemoradiotherapy and control tamoxifen (p>0.05); regional macular thickness revealed that only one macular field showed a significant difference between two groups; in the external nasal macular field, the chemoradiotherapy patients showed thinner retinal thickness compared to the control. We conclude that breast cancer patients exposed to chemotherapy and hormone therapy presented: unfavorable lipid profile with high levels of total cholesterol, LDL, triglycerides and low HDL, overweight and obesity, lower antioxidant capacity for patients who received chemotherapy and systemic levels of inflammatory cytokines, TNF-α and IL-6, elevated; there was a weak association between plasma concentrations of tamoxifen and its active metabolites with levels of HDL-c, LDL-c and VLDL-c, with a low impact of lipoprotein levels on exposure to tamoxifen, 4-hydroxytamoxifen and endoxifen; a macular field was altered in the chemotherapy group, which had a thinner retina compared to the control group, however the retinal structure was sensitive to the presence of tamoxifen metabolites.