Nutritional factors and metabolic biomarkers: impact in risk and survival of women with breast cancer

Author(s)

Isabelle Romero Novelli

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Saúde Pública (FSP/CIR)
• Defense date: 2022-12-16

Examining board members

Nágila Raquel Teixeira Damasceno; Gabriela Villaça Chaves; Fernando Salvador Moreno

• Advisor: Nágila Raquel Teixeira Damasceno; Alfredo Carlos Simoes Dornellas de Barros

Abstract

Breast cancer (BC) is the most common cause of cancer and the leading cause of death in women. BC is a complex disease and distributes in distinct molecular subtypes regarding the expression of estrogen receptor (ER), progesterone receptor (PR), receptor tyrosine-protein kinase erbB-2 (HER2), and Ki67 protein status. Although BC is multifactorial evidence indicates that nutritional factors are relevant during steps of carcinogenesis, recurrence, and survival. We aim to assess the role of nutrition status and metabolic biomarkers in women with BC. This is a case-control study between May 2011 and August 2012. In the case group, there was a follow-up until April 2019, characterizing a cohort study. From these groups, different manuscripts were structured with different study designs according to each hypothesis. Manuscript 1 - cohort based on the follow-up of the BC group, Manuscript 2 - a cross-sectional study with women with Luminal A BC (ER positive, PR positive/negative, HER2 negative, Ki67 low) and Manuscript 3 - a cross-sectional case-control study. Data were obtained by medical records, interviews and anthropometric parameters with electrical impedance. Blood samples were collected after 12-hour fasting to analyze serum glucose, glycated hemoglobin, insulin growth factor 1 (IGF-1), insulin growth factor binding protein (IGFBP-3), insulin and adipokines, thiobarbituric acid reactive substances (TBARS), non-esterified fatty acids (NEFA), DNA oxidative damage (8-OH-dG) and lipoproteins (total cholesterol - TC, Low-density lipoprotein cholesterol - LDL-c, high-density lipoprotein cholesterol - HDL-c and triacylglycerols) and fatty acid profile of erythrocyte membrane. All statistical tests were performed using Statistical Package for Social Sciences® (SPSS), version 21.0. Statistical significance was set at p < 0.050. The main results of the study showed that premenopausal women with BC and clinical staging (CS) between II and III had a more atherogenic lipid profile characterized by the decrease in HDL-c, increase in LDL-c, non-HDL-C and apolipoprotein B (Apo B). We highlight that women with BC and high LDL-c and non-HDL-c had increase odd of having larger tumor size whereas HDL-c was associated with a decreased risk. Premenopausal women with BC had an increased level of TBARS and NEFA at diagnosis and had a lower survival probability. Additionally, women with Luminal A BC had higher serum levels of glucose, IGF-1, IGFBP-3, IL1&beta;, IL6, and lower IL10 compared to its matching controls. Also, women with increased serum levels of TBARS, glucose, and insulin increased risk of Luminal A BC, and higher levels of adiponectin decrease the risk of developing Luminal A BC when controlled by menopause status and BMI. Women with BC presented impaired IGF-1/insulin axis, sustained by overweight/obesity and higher central adiposity. Increased levels of serum glucose, insulin, and IGF-1 showed higher odds to developing BC. In conclusion, our results demonstrate the relevant impact of metabolic biomarkers on risk of developing BC and in survival outcomes. This study reinforces the relevance to increase prevention strategies regarding lifestyle and nutrition to decrease incidence and improve outcome of BC. (AU)

• FAPESP's process: 18/18739-6 - Role of Insulin Growth Factor 1 (IGF-1) on body composition, oxidative stress, type of tumor and survival in women with Breast Cancer
• Grantee: Isabelle Romero Novelli
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)