How Can Biomarkers Create a Diagnostic Complement to Imaging?
Current methods of breast cancer detection rely on imaging technologies, such as mammography, which provide a visual interpretation of breast abnormalities. By adding a biochemical approach to detection, we can help simplify clinical decision making. This innovative molecular approach is needed to complement current imaging techniques and allow for early breast cancer detection at a more precise level. Tumors become invasive due to numerous cellular changes. As cellular growth progresses, the primary tumor will begin shedding invasive cells and the body’s own immune system releases autoantibodies early in response to the tumor due to the presence of altered DNA, RNA and/or proteins (i.e. autoantibodies target tumor proteins). These tumor proteins are detectable within the bloodstream and are indicative of specific cancers.
Theoretically, very small tumors can be detected long before they are visible on imaging, which typically requires a tumor to be greater than 5mm in size to definitively identify the tumor. Imaging also has its limitations, even when tumors are of a detectable size. These limitations include:
- False positive results: Imaging sometimes leads to follow-up examinations, including biopsies, when there is no cancer. A false-positive is most likely following a woman's initial screening mammogram.
- False negative results: False-negative results occur when mammograms appear normal even though breast cancer is present. Overall, screening mammograms miss about 20% of breast cancers that are present at the time of the screening.
- Overtreatment and overdiagnosis: Overtreatment and overdiagnosis might be caused by screening mammograms that lead to medical interventions for certain cases of ductal carcinoma in situ (DCIS) that may never have become clinically apparent, would have not caused a woman any harm in her lifetime, would not have progressed or needed treatment, or otherwise been detected in the absence of screening.
- Radiation exposure: Radiation exposure is a risk factor for breast cancer. Overall risk from a single exposure from mammography is very small. However, the risk increases with the amount of exposure and with exposure at younger ages.
- Variability of pathologists diagnosed on the interpretation of breast biopsy specimens: The pathologist’s diagnosis of breast tissue ranges from benign without atypia, to atypia, to DCIS, to an invasive breast. Misclassification of breast lesions may contribute to either over treatment or under treatment of lesions identified during breast screening.
How Can Biomarkers Help?
A blood test that utilizes a simple, noninvasive approach for the detection of breast cancer would significantly reduce the number of false positive and false negative results in women with abnormal or difficult-to-interpret imaging findings. It would also decrease the cost and burden on the patient.
This type of test is referred to as a “liquid biopsy”, which utilizes bodily fluids such as serum or saliva. In recent times, hundreds of millions of dollars have been invested in the development of liquid biopsy tests. Dozens of companies in the US alone are working to develop different liquid biopsy technologies to improve breast cancer detection.
A liquid biopsy that utilizes a combination of protein biomarkers to aid in the detection process of breast cancer could serve as the ideal diagnostic complement. A biomarker, as defined by the National Cancer Institute, is “a biological molecule found in the blood, other body fluids, or tissues that is a sign or a normal or abnormal process, or of a condition or disease”. Cancer biomarkers are associated with multiple stages during the disease progression and therefore, may play a significant role in clinical decision making. By looking at biomarkers, diagnostics tests can provide information about early tumor development to detect breast cancer in a more accurate and timely manner.
A biomarker based liquid biopsy tool we can increase a woman’s chance of surviving breast cancer by improving early detection and ruling out lesions that are not clinically significant. This is particularly useful for women with dense breasts who have abnormal imaging results. A liquid biopsy tool that worked in conjunction with imaging would have the power to reduce uncertainty patients face by reducing false positive and negative results, as well as giving a more definitive diagnosis to patients with abnormal or unclear imaging.