Nutrients and nipple aspirate fluid composition: the breast microenvironment regulates protein expression and cancer aetiology

Abstract

The aetiology of breast cancer is complex and multifactorial, and may include diet and xenobiotic compounds. A change in diet affects nutrient levels in blood, but to what extent diet can affect micronutrient concentrations in the breast is not yet well established. Breast nipple aspirate fluids (NAF) can be non-invasively obtained from the breast in most women; it represents a biological tool to assess metabolic changes in the breast ductal microenvironment. A wide variation in biomolecular and hormonal composition of NAFs collected from healthy and breast cancer patient may be due to genetic and nutritional factors; however, micro-and macro-nutrients may influence the secretory status of these women, thus NAF composition and risk of breast carcinoma. The aim of this overview is to highlight the detrimental/beneficial role that diet-related compounds in nipple aspirate fluid can have in breast cancer risk.Keywords Nutrigenomics Á Diet Á Benign breast diseases Á Breast cancer Á Nipple aspirate fluids Á Nutrients Gene-diet interactions and breast cancer riskBreast cancer aetiology is complex, and many factors (both environmental and genetic) contribute to it. Of the environmental factors, the link between diet and BC risk has long been recognized [35]. Because benign breast disease (BBD), particularly atypical hyperplasia (AH), is a marker of increased BC risk, studies of diet and BBD have provided evidence about the effect of diet at an early stage in the process of breast carcinogenesis, reporting also some contrasting results [26,52]. It is well known that high consumption of fruit and vegetable has been thought to provide protection against many types of cancer, including BC [15]. Their consumption could decrease BC risk through several mechanisms, mainly linked to the abundance of antioxidants contained therein, which also contain biocompounds such as isoflavones, lignans and indoles [1,2,64]; all of these substances have been convincingly shown to have anticarcinogenic properties and strong effects on estrogen metabolism (as reviewed in [38]), even though to date there are contrasting findings [35].It is becoming clear that relationships between diet and breast cancer aetiology are extremely complex, and that the impact of micro-and macro-nutrients on BC risk are dependent in part on genetic factors [20,21,58]. Being the application of molecular epidemiology to nutrition and breast cancer in its infancy, recent studies have highlighted the importance of investigations of diet, genetic variability and breast cancer risk using a fluid non-invasively collected from breast ducts (nipple aspirate fluid, NAF), a fluid that mirrors the microenvironment of the breast tissue during physio-pathological conditions [29,43,44,56]. Nipple aspirate fluid, a window on the breast tissue microenvironmentThe ductal system of the breasts of non-pregnant women produces proteinaceous secretions-containing chemicals of endogenous and exogenous origin as well as epithelial cells-which can be sampled and utilized for breas...

Analysis of aluminium content and iron homeostasis in nipple aspirate fluids from healthy women and breast cancer‐affected patients

“…It can be obtained in more than 90% of pre‐ and post‐menopausal women and is a low‐cost procedure causing minimal or no discomfort (Sauter, ). NAF contains secreted proteins and cells shed from ductal and lobular epithelium (Mannello et al , ), and several biomarkers (Petrakis, , ; Mannello et al , , ) and proteinases (Mannello and Sebastiani, ; Qin et al , ) of potential use as epidemiological and clinical research tools have been identified (Dua et al , ). In addition, the intracrinology of NAF has provided a further panel of cancer biomarkers reflecting the hormonal status in the breast microenvironment (Mannello et al , ).…”

High-Throughput Proteomic Profiling of Nipple Aspirate Fluid from Breast Cancer Patients Compared with Non-Cancer Controls: A Step Closer to Clinical Feasibility

“…During our analysis, we identified one sample from the diseased breast of a patient with invasive carcinoma to be of a red color (BC7), whilst the NAF of healthy breast origin was described as yellow; all other IC samples were labelled as brown, yellow or white with one olive-green sample being an exception. The color of NAF has since been strongly linked with dietary intake, and a red/brown discoloration being attributed to lipids levels (mainly as oxidized cholesterol end-products) and green discoloration linked with an absence of lactose intake [ 32 ].…”

An Improved Breast Epithelial Sampling Method for Molecular Profiling and Biomarker Analysis in Women at Risk for Breast Cancer

“…In this report, we describe a breast epithelial sampling method that increases epithelial cell yield and cell homogeneity for molecular profiling, which should significantly expand the analysis of at-risk breast tissue for biomarkers and for molecular changes of early breast carcinogenesis. The technique allows for collection of multiple aliquots of the entire contents of the ductal microenvironment, including ductal fluid with its multiple components, 14,[26][27][28] and provides for a median of eight samples of 5,000 epithelial cells per sample, and a median six samples consisting of 90% pure epithelial cells. Samples are proven to be free of inhibitory substances.…”