Non-Invasive Biomarkers for Early Detection of Breast Cancer

For decades, mammograms have been the gold standard for population-based and opportunistic breast cancer screening in many high-income countries. However, there are debates on whether mammograms are the best screening tool due to certain limitations. These include the risk of overdiagnosis, radiation exposure, and difficulty in detecting small tumors. Additionally, mammograms may have lower accuracy in detecting tumors in dense breasts, which can then require further examination by ultrasound or magnetic resonance imaging (MRI). Due to these challenges, researchers are actively working on developing biomarker tests that could revolutionize the way breast cancer is detected both at first diagnosis and at recurrence of previously treated breast cancer, allowing for non-invasive and specific detection of cancer characteristics.

A biomarker, according to the National Institutes of Health Biomarkers Definitions Working Group, is

“a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”

In short, it is a biological compound that can be used to identify specific biological processes that are happening within a body. By detecting and/or measuring certain biological compounds, one can potentially tell if a person has a certain disease, such as cancer.

Blood-based biomarkers

Blood-based biomarker tests detect certain components in blood, such as cancer-specific proteins, nucleic acids, or other cellular vesicles (small fluid-filled sacs) and live cells or dead cell debris shed by cancer cells in blood samples. A blood draw for biomarkers is only minimally invasive and could be a much faster and more convenient alternative to invasive needle and surgical biopsies. For breast cancer detection, blood-based biomarkers are used to detect the following:

• Circulating Carcinoma Proteins
• Circulating Tumor Cells
• Circulating Cell-Free Tumor DNA (ctDNA)
• Circulating miRNAs
• Extracellular Vesicles

Non-blood-based biomarkers

Other body fluids such as urine, sweat, nipple aspirate fluid (NAF), tears, and volatile organic compounds (VOCs) in exhaled breath have also been investigated to detect certain biomarkers in breast cancer patients.

• Biomarkers in urine
• Biomarkers in sweat
• Biomarkers in NAF
• Biomarkers in tears
• Biomarkers in exhaled breath

The importance of non-invasive biomarkers in detecting breast cancer at an early stage cannot be overstated. These biomarkers offer a valuable source of quantitative data that can improve the accuracy of diagnosis. This contrasts the qualitative nature of mammograms, which also have its fair share of limitations. Adding non-invasive biomarkers to the existing screening and diagnostic methods can significantly enhance the early detection of breast cancer, thereby improving the chances of successful treatment and recovery.

No blood or other biomarkers have been found to be sensitive or specific to be used for breast cancer screening or detection/diagnosis of early-stage or metastatic breast cancer, but active research in this area is ongoing.

Currently, only the personalized tumor-informed circulating tumor DNA test called Signatera has been validated and approved to be used to detect recurrence of treated breast cancer. The effectiveness of cancer medicines to prevent breast cancer recurrence once ctDNA is detected in blood is being studied in multiple clinical trials.