Trace elements as tumor biomarkers and prognostic factors in breast cancer: a study through energy dispersive x-ray fluorescence

Marina P Silva,Danilo F Soave,Alfredo Ribeiro-Silva,Martin E Poletti

doi:10.1186/1756-0500-5-194

Marina P Silva, Danilo F Soave + Show 2 more

Open Access

https://doi.org/10.1186/1756-0500-5-194

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Abstract

BackgroundThe application and better understanding of traditional and new breast tumor biomarkers and prognostic factors are increasing due to the fact that they are able to identify individuals at high risk of breast cancer, who may benefit from preventive interventions. Also, biomarkers can make possible for physicians to design an individualized treatment for each patient. Previous studies showed that trace elements (TEs) determined by X-Ray Fluorescence (XRF) techniques are found in significantly higher concentrations in neoplastic breast tissues (malignant and benign) when compared with normal tissues. The aim of this work was to evaluate the potential of TEs, determined by the use of the Energy Dispersive X-Ray Fluorescence (EDXRF) technique, as biomarkers and prognostic factors in breast cancer.MethodsBy using EDXRF, we determined Ca, Fe, Cu, and Zn trace elements concentrations in 106 samples of normal and breast cancer tissues. Cut-off values for each TE were determined through Receiver Operating Characteristic (ROC) analysis from the TEs distributions. These values were used to set the positive or negative expression. This expression was subsequently correlated with clinical prognostic factors through Fisher’s exact test and chi-square test. Kaplan Meier survival curves were also evaluated to assess the effect of the expression of TEs in the overall patient survival.ResultsConcentrations of TEs are higher in neoplastic tissues (malignant and benign) when compared with normal tissues. Results from ROC analysis showed that TEs can be considered a tumor biomarker because, after establishing a cut-off value, it was possible to classify different tissues as normal or neoplastic, as well as different types of cancer.The expression of TEs was found statistically correlated with age and menstrual status. The survival curves estimated by the Kaplan-Meier method showed that patients with positive expression for Cu presented a poor overall survival (p < 0.001).ConclusionsThis study suggests that TEs expression has a great potential of application as a tumor biomarker, once it was revealed to be an effective tool to distinguish different types of breast tissues and to identify the difference between malignant and benign tumors. The expressions of all TEs were found statistically correlated with well-known prognostic factors for breast cancer. The element copper also showed statistical correlation with overall survival.

Highlights

The application and better understanding of traditional and new breast tumor biomarkers and prognostic factors are increasing due to the fact that they are able to identify individuals at high risk of breast cancer, who may benefit from preventive interventions
Biomarkers are any type of measurable element which is able to demonstrate the presence of malignancy or malignant potential, or to predict the behaviour of the tumor, the prognosis or the treatment response [6]
The role of trace elements has not yet been well established in literature, the increase in tumor tissues may be related to metabolic and structural aspects [17,29,57,58,59,60], which indicates its potential as a tumor biomarker

Summary

Introduction

The application and better understanding of traditional and new breast tumor biomarkers and prognostic factors are increasing due to the fact that they are able to identify individuals at high risk of breast cancer, who may benefit from preventive interventions. Diagnosis and therapeutic approach for breast cancer is based on predictive and prognostic factors which are well-established for this disease Prognostic factors such as tumor size, lymph nodal status, TNM staging information, histological grade and type, mitotic figure counts and hormone receptor status have proven to be of prognostic importance and useful in clinical patient management [1]. A better understanding and application of traditional tumor biomarkers and the identification of new markers is essential since they improve the patients quality of life by sparing them from going under toxic treatments that are unlikely to benefit them, and by making it possible to establish an appropriate individualized treatment for each type of tumor, avoiding unnecessary treatment [5,6]

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