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

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.

Role of Ca, Fe, Cu and Zn in breast cancer: study by X‐ray fluorescence techniques and immunohistochemical analysis

“…Therefore, this element can comprise a double function: Iron deficiency can speed up tumor growth because of angiogenesis activation, whereas its excess can promote the transformation of normal cells into neoplastic cells by inducing oxidative stress. [40,46] clinicopathological data are on Silva et al [13] Figure 7(a and b) shows that the negative expression of iron occurs most often in young and premenopausal women, probably because of the fact that the systemic iron concentration is lower in women under these conditions. [47] Figure 7(a) also shows that the positive expression of Fe is higher in older women, probably because of the accumulation of this element in the organism due to menopause.…”

“…For example, if Ca concentration was above 212.6 mg/kg, the tissue can be classified as malignant. See reference Silva et al [13] On the basis of the cut-off values, trace element expression was determined. If the trace element concentration in a tissue was above the cut-off point, the trace element expression in that tissue was considered positive, and if trace element concentration in a tissue was below the cut-off point, then the trace element expression in that tissue was considered negative.…”

“…Complete clinicopathological data are described by Silva et al 2012. [13] To perform energy dispersive XRF (EDXRF) measurements, each sample was cut in 1-cm-thick and 1-cm-long sections, and placed in a specific sample holder, covered by Kapton W film.…”

“…Specifically, our group has focused on the study of four elements: Ca, Fe, Cu and Zn. [5,6,9,12,13] In neoplastic breast tissues, calcium is usually associated with microcalcifications, both in benign and malignant tumors. [14] Although the diagnostic value of microcalcifications in breast cancer is of great importance, a significant point is to know if their presence is an indicative of degeneration or an active process of the cell.…”

High serum iron and zinc decrease glutathione S-transferase among women with breast cancer

“…On the other hand, research by Silva et al (9) showed that concentrations of trace elements are higher in neoplastic tissues (malignant and benign) when compared with normal tissues. Thus, there is still inconsistency of research results on the effect of trace element level on breast cancer.…”