**1. Introduction**

Cancer is considered a complex disease because several factors are involved the disease outbreak [1]. Breast cancer (BCa) is among the most common cancers in women, accounting for about 14% of deaths from cancer in women around the world. In both the developed and less developed world, breast cancer is the most common cancer in women. About 508,000 women worldwide are estimated to have died from breast cancer in 2011 [2].

One of the most important methods is the detection and analysis of cancer biomarkers. The development of cancer has the maximum potential for therapeutic intervention. Recent developments in molecular biology have made it clear that biomarkers of cancer play a major role in the treatment, prognosis and insight into cancer etiology. The National Cancer Institute describes a biomarker as a "biological molecule contained in blood, other body fluids or tissues that is a sign of a normal or abnormal process or disease or disorder."

Cancer markers are one of the most valuable tools for early detection, diagnosis, treatment, progression tracking and evaluation of chemotherapy resistance. There are over 200 different cancer-related diseases impacting various parts of the human body. Tumor markers are usually found at low levels in the absence of a tumor. After tumor formation, level changes and therefore cancer marker clinical tests must be fast, selective and sensitive sufficiently distinguish slight changes in marker levels in complex biological fluids.

Eventually, the extensive use of tumor markers in healthcare would rely on the identification of many highly selective and sensitive tumor markers. However, traditional immunoassays such as enzyme-linked immunosorbent assay (ELISA) have some drawbacks including time-consuming, extensive incubation procedures are performed for the antibody-antigen interaction to reach equilibrium and performed by highly skilled personnel using costly and sophisticated instruments.

## **1.1 Electrochemical immunosensors: definitions and methods**

Over the past decade, a growing number of researchers have focused on developing fast and simple-to-use biosensor technology-based techniques to detect specific biomarkers. Under the proposed International Union of Pure and Applied Chemistry (IUPAC) concept, a biosensor combines two important components of the bioreceptor and the transducer component for target detection. The chemical biosensors have enticing instruments that can be measured to convert biological interactions into electric signals. Nevertheless, the conversion of biological signal to a measurable signal is difficult due to the limitations of the biological environment and the extremely low tumor marker rates in biological samples.

The development of effective biosensors with sensitivity and selectivity has thus gained significant emphasis not only in clinical medicine, as well as in basic medicine and biomedical engineering. It is not surprising that due to their high potential in the bioassay region, the emphasis has been shifted to electrochemical biosensors as shown in **Figure 1**.

In addition to, they promote the reuse of molecules in biorecognition and prevent a time lapse among sample preparation and analysis. Moreover, biosensors have high potential to detect multiple biomarkers simultaneously. The use of electrochemical biosensors is particularly noteworthy due to their low cost, usability, sensitivity, specificity and suitability to detect low levels of molecular biomarkers

**89**

*Current and Prospective of Breast Cancer Biomarkers DOI: http://dx.doi.org/10.5772/intechopen.91151*

obtained with various manufacturing techniques.

reviewed in the following sections.

marker using [Fe(CN)6]

0.001–40 ng mL<sup>−</sup><sup>1</sup>

low detection limit of 100 fg mL<sup>−</sup><sup>1</sup>

limit was estimated at 0.00045 ng mL<sup>−</sup><sup>1</sup>

**2.1 Carcinoembryonic antigen (CEA)**

**2. Immunoassays with biomarkers for breast cancer**

using a range of available techniques like cyclic voltammetry (CV); differential pulse voltammetry (DPV); square-wave voltammetry (SWV) and electrochemical impedance spectroscopy (EIS). On the other hand, the electrochemical biosensors

In this chapter, we addressed the molecular changes throughout cancer that have been developed and related biomarkers. Currently designed biosensor platforms and manufacturing methods to identify these biomarkers of cancer are discussed. Compared to the previous studies, this analysis highlights these biosensors analytical performance in terms of sensitivity, linear detection range and detection limit

Cancer biomarkers are molecules in the presence of cancer in the body that are overexpressed. It can apply to a secreted enzyme triggered by a tumor or a specific body response to cancer. It is important to use a wide range of genomic, epigenetic, glycomic, proteomic and imaging biomarkers to recognize the point, prognosis, and epidemiology of cancer. Despite the fact that there are still multiple obstacles in turning the analysis of biomarkers into a therapeutic platform; several biomarkers dependent on genes and proteins have now been used. These biomarkers are

One of the first tumor antigens to be reported was carcinoembryonic antigen (CEA), defined in 1965. CEA is a glycoprotein of the immunoglobulin family found by radioimmunoassay or enzyme-linked immunosorbent assay in the serum of patients with cancer. A strong false positive rate in common communities and a poor test sensitivity and accuracy reduce the therapeutic benefit of CEA identification. The elevated CEA level is not unique to breast cancer because CEA can be present in many various neoplasia forms. CEA is more prevalent in ductal than in lobular carcinomas in breast tumors. During the testing process, the FDA also identified CEA as an acceptable serum biomarker for colon cancer [3]. For detection of CEA, numerous electrochemical immunosensors have been developed [4–7]. Rizwan et al. [4] fabricated the nanocomposite of gold nanoparticles (AuNPs), carbon nano-onions (CNOs), single-walled carbon nanotubes (SWCNTs) and chitosan (CS) (AuNPs/CNOs/SWCNTs/CS) for the modification of GCE (glass carbon electrode) and development of highly sensitive label-free electrochemical immunosensor for the detection of carcinoembryonic antigen (CEA), clinical tumor

of the immunosensors were observed using CV and SWV methods. When CEA antibody combines with CEA antigen, the formed immunocomplexes formed. The decrease in the electrical signals of the immunosensor has a linear relationship for

immunosensors [5] for detecting CEA based on gold nanoparticles (AuNPs) and Nile blue A (NB) hybridized electrochemically reduced graphene oxide (NB-ERGO) as shown in **Figure 2**. The NB-graphene oxide (NB-GO) composite was developed by the π-π interaction. The linear range of the proposed immunosensor was estimated at

(AgNPs) decorated with thionine/infinite coordination polymers as sensing platforms

the quantitative detection of CEA ranging from 100 fg mL<sup>−</sup><sup>1</sup>

3/4<sup>−</sup> as mediator solution. By using layer by layer fabrication

under optimal conditions using DPV technique and the detection

. Interestingly, a novel label-free electrochemical

for CEA. In addition, a silver nanoparticle

to 400 ng mL<sup>−</sup><sup>1</sup>

with a

play a major role in moving towards simpler point-of-care (POC) research.

**Figure 1.** *The construction of breast cancer biomarkers-based biosensors.*

#### *Current and Prospective of Breast Cancer Biomarkers DOI: http://dx.doi.org/10.5772/intechopen.91151*

*Molecular Biotechnology*

in complex biological fluids.

as shown in **Figure 1**.

body. Tumor markers are usually found at low levels in the absence of a tumor. After tumor formation, level changes and therefore cancer marker clinical tests must be fast, selective and sensitive sufficiently distinguish slight changes in marker levels

Eventually, the extensive use of tumor markers in healthcare would rely on the identification of many highly selective and sensitive tumor markers. However, traditional immunoassays such as enzyme-linked immunosorbent assay (ELISA) have some drawbacks including time-consuming, extensive incubation procedures are performed for the antibody-antigen interaction to reach equilibrium and performed

Over the past decade, a growing number of researchers have focused on developing fast and simple-to-use biosensor technology-based techniques to detect specific biomarkers. Under the proposed International Union of Pure and Applied Chemistry (IUPAC) concept, a biosensor combines two important components of the bioreceptor and the transducer component for target detection. The chemical biosensors have enticing instruments that can be measured to convert biological interactions into electric signals. Nevertheless, the conversion of biological signal to a measurable signal is difficult due to the limitations of the biological environment

The development of effective biosensors with sensitivity and selectivity has thus gained significant emphasis not only in clinical medicine, as well as in basic medicine and biomedical engineering. It is not surprising that due to their high potential in the bioassay region, the emphasis has been shifted to electrochemical biosensors

In addition to, they promote the reuse of molecules in biorecognition and prevent a time lapse among sample preparation and analysis. Moreover, biosensors have high potential to detect multiple biomarkers simultaneously. The use of electrochemical biosensors is particularly noteworthy due to their low cost, usability, sensitivity, specificity and suitability to detect low levels of molecular biomarkers

by highly skilled personnel using costly and sophisticated instruments.

**1.1 Electrochemical immunosensors: definitions and methods**

and the extremely low tumor marker rates in biological samples.

**88**

**Figure 1.**

*The construction of breast cancer biomarkers-based biosensors.*

using a range of available techniques like cyclic voltammetry (CV); differential pulse voltammetry (DPV); square-wave voltammetry (SWV) and electrochemical impedance spectroscopy (EIS). On the other hand, the electrochemical biosensors play a major role in moving towards simpler point-of-care (POC) research.

In this chapter, we addressed the molecular changes throughout cancer that have been developed and related biomarkers. Currently designed biosensor platforms and manufacturing methods to identify these biomarkers of cancer are discussed. Compared to the previous studies, this analysis highlights these biosensors analytical performance in terms of sensitivity, linear detection range and detection limit obtained with various manufacturing techniques.
