Non-Invasive Biomarkers for Early Detection of Breast Cancer

Abstract

Breast cancer is the most common cancer in women worldwide. Accurate early diagnosis of breast cancer is critical in the management of the disease. Although mammogram screening has been widely used for breast cancer screening, high false-positive and false-negative rates and radiation from mammography have always been a concern. Over the last 20 years, the emergence of "omics" strategies has resulted in significant advances in the search for non-invasive biomarkers for breast cancer diagnosis at an early stage. Circulating carcinoma antigens, circulating tumor cells, circulating cell-free tumor nucleic acids (DNA or RNA), circulating microRNAs, and circulating extracellular vesicles in the peripheral blood, nipple aspirate fluid, sweat, urine, and tears, as well as volatile organic compounds in the breath, have emerged as potential non-invasive diagnostic biomarkers to supplement current clinical approaches to earlier detection of breast cancer. In this review, we summarize the current progress of research in these areas.

Keywords: biomarker; blood; body fluid; breast cancer; detection; diagnosis.

Figure 1

Overview of current sources and main measurement types of non-invasive biomarkers for early detection of breast cancer. Figures were created with BioRender.com (https://biorender.com/).

Figure 2

Diagram of the procedures of breast cancer detection through methylation patterns of circulating cell-free DNA in the blood. Breast tumor and normal tissue shed DNA fragments into the blood. Peripheral blood is withdrawn from human subjects and circulating tumor DNA (ctDNA) is isolated from the blood sample. The methylation status of the ctDNA is determined by targeted bisulfite methylation sequencing. The methylation patterns of the ctDNA fragments are analyzed. The presence or absence of cancer cells is thus determined by comparing the methylation patterns with those in the methylation database, which is constructed from those individuals with and without cancer. The origin of cancer is determined using unique tissue-specific methylation patterns. Figures were created with BioRender.com (https://biorender.com/).