List of breast cancer biomarkers

Breast imaging is crucial in the screening, diagnosis, and preoperative work-up of breast cancer. However, imaging is expensive and cumbersome, and the use of iodine-based or gadolinium contrast can cause toxicity. Moreover, the disease may progress on an ineffective treatment for a significant time before additional imaging is obtained. Biomarkers can provide additional insight into a patient’s prognosis and response to treatment¹.

Biomarkers refer to biological substances present in blood, various bodily fluids or tissues that serve as indicators of a regular or irregular biological process, or the presence of a specific condition or illness. In the context of cancer, biomarkers can be produced by the cancer tissue itself or by the body in response to cancer. They are a cornerstone of precision medicine, allowing for more targeted diagnosis and treatment². They can be molecular, histologic, radiographic, or physiological features.

Biomarkers are not only associated with malignant disease but can also be seen in other conditions like cardiovascular, neurological, or other inflammatory diseases. Examples of cancer biomarkers include prostate-specific antigen (prostate cancer), cancer antigen 125 (CA125) for ovarian cancer, HER2 (breast cancer), EGFR mutations (lung cancer), and KRAS mutation for colorectal cancer.

On the other hand, non-cancer biomarkers include Troponin (cardiac damage), Brain natriuretic peptides (BNP) for heart failure, Thyroid stimulating hormone for thyroid disorders, and HbA1c (Glycated Hemoglobin) for long term glucose control in diabetes. In cancer and non-cancer contexts, these biomarkers aid in disease detection, monitoring, and treatment decisions.

In recent times, advances in breast cancer biomarker testing have been shown to slow down disease progression and even result in better prognosis. This showcases the diverse applications of biomarker technology in healthcare.

Biomarkers are essential to the healthcare industry because they offer quantifiable indicators that can help with diagnosis, prognosis, and monitoring of various medical problems. These molecular, biochemical, or cellular entities serve as objective measures that offer a glimpse into the dynamic nature of an individual’s health status.

Whether in blood, tissues, or other bodily fluids, biomarkers can signify normal biological processes or highlight deviations associated with diseases.

Biomarker testing in cancer treatment

In cancer, biomarker testing contributes to improved and accurate diagnoses, which enables healthcare practitioners to tailor treatment plans based on individual patient profiles. Early detection potential is important, resulting in enhanced patient outcomes as interventions can be initiated promptly. It allows doctors to precisely target a specific cancer so patients may not have to undergo more generalized treatments like chemo and radiation that may not work as well for them³.

Biomarkers accurately diagnose other disease conditions ranging from neurodegenerative disorders to cardiovascular ailments, enabling prompt treatments and customized medicinal strategies.

In the modern healthcare system, biomarkers are important resources that help doctors understand diseases more deeply and provide more individualized, successful therapies.

Modern biomarker testing offers essential insights into the molecular properties of cancer and has transformed the diagnosis of cancer, especially breast cancer.

There are many advantages of biomarker testing for breast cancer diagnosis as discussed subsequently, with emphasis on enhanced and precise diagnosis, the potential for early detection, accessibility, affordability, and the possibility of individualized medical itineraries.

Improved and accurate diagnosis

Biomarkers can also aid in the diagnosis of cancer. Although many cancers are diagnosed by looking at cells under a microscope, it can sometimes be difficult to determine the primary type of tumor in cases where cancer has spread to more than one location. Biomarkers may help determine this⁴. The use of biomarker testing is essential for improving the precision of breast cancer diagnosis. By using biomarker testing instead of conventional techniques like imaging, it is possible to acquire a deeper insight into tumors’ molecular composition. This comprehensive understanding helps distinguish between different breast cancer subtypes and allows physicians to individualize treatment regimens better.

Early detection potential – leading to improved patient outcomes

The ability of biomarker testing to aid in early cancer diagnosis is one of its most significant benefits. Prompt detection of particular biomarkers linked to breast cancer enables prompt intervention, which may promote patient outcomes. According to the American Cancer Society, when breast cancer is detected early, and is in the localized stage, the 5-year relative survival rate is 99%⁵.

Early diagnosis is frequently associated with a higher likelihood of success and more controllable therapy options.

Accessibility and affordability

Several technological developments in biomarker testing have reduced the cost and increased the accessibility of these diagnostic instruments.

Biomarker analysis is increasingly being used as a routine component of cancer diagnosis due to the advent of affordable testing techniques. By making biomarker testing more accessible, more people can take advantage of its benefits, which results in a greater prevalence of early diagnosis.

Personalized medical journey

In recent years, targeted medicines have offered dramatic advancements in cancer care outcomes across a wide variety of cancer types⁶. Biomarker testing facilitates a personalized approach to cancer treatment. Physicians can direct treatment plans to individual patients by identifying specific molecular characteristics of tumors. This personalized medical journey minimizes the one-size-fits-all approach, which leads to more effective and targeted therapies that improve overall patient outcomes.

In the presence of breast cancer, the cancer cells and other body cells tend to produce biomarkers associated with breast cancer. For an accurate diagnosis and course of therapy, knowledge of the several biomarkers related to breast cancer is fundamental.

Some common breast cancer biomarkers, as will be further discussed below, include hormone receptor status, human epidermal growth factor receptor 2 (HER2), thymidine kinase, CA 15-3 and CA 27.29, Ki67, and cell-free DNA (cfDNA). Each biomarker serves a unique purpose in characterizing the disease and guiding treatment decisions.

Hormone receptor status

Some breast cancer cells are sensitive to hormones like estrogen and progesterone because they contain the hormone receptors, which are the biomarkers. These receptors play essential roles in cancer growth and development and help determine how invasive the tumor can be. Most invasive breast cancers (75–80%) are hormone receptor (HR) positive, and estrogen receptor (ER)-positive tumors have been found to demonstrate improved survival following endocrine therapy⁷. The knowledge of their status helps determine the appropriate hormonal therapies for treatment. While advantageous in directing hormone-based treatments, the limitations lie in cases where tumors lack these receptors.

Human epidermal growth factor receptor 2 (HER2)

The HER-2/neu oncogene is a member of the erbB-like oncogene family, and is related to, but distinct from, the epidermal growth factor receptor. This gene is amplified in human breast cancer cell lines. HER-2/neu was found to be amplified from 2- to greater than 20-fold in 30% of the tumors⁸.

The determination of HER2 is essential in any patient with a proven invasive form of breast cancer. It is positive when there is evidence of gene amplification or protein overexpression.

About 70% of breast cancer patient cases are defined as having low HER2⁹.

Physicians might recommend a HER2-targeted therapy if the breast cancer subtype is HER2-positive. There have been notable advancements in response rates and survival with HER2-targeted therapy, beginning with monoclonal trastuzumab in conjunction with chemotherapy and endocrine therapy.

Thymidine kinase (TK)

Thymidine kinase is an enzyme essential for DNA synthesis and a good marker of cellular proliferation. TK1 activity in the blood are higher in metastatic breast cancer patients than in healthy individuals. Thymidine kinase (TK) activity is measured by radioenzymatic assay¹⁰.

The DiviTum® (Dividing Tumor) TKa test quantifies the activity of thymidine kinase in the bloodstream. With the result of the test, combined with other methods of disease monitoring, medical practitioners can understand better the progression of the cancer and optimize patient treatment outcomes.

Unlike some other breast cancer biomarker tests, thymidine kinase activity testing does not require biopsy or surgery to get the tissues for the investigation. As a blood-based biomarker, blood samples of patients can be used for analysis. The setback of this biomarker is the limited research to establish its widespread utility.

CA 15-3 and CA 27.29

Cancer antigens 15-3 (CA15-3) and CA 27.29 represent sequences of proteins overexpressed in malignant epithelial cells, as seen in breast cancer. They are suitable measures of the cancer prognosis. For breast cancer that has spread to other organs, tumor markers that might be checked include carcinoembryonic antigen (CEA), cancer antigen 15-3 (CA 15-3), and cancer antigen 27-29 (CA 27-29). Blood tests for these tumor markers are not used by themselves to diagnose or follow breast cancer¹¹.

Ki67

Ki-67, also known as Antigen Ki-67, is a protein associated with cellular proliferation and a prognostic factor of breast cancer. In cancer that is estrogen receptor positive, a higher level of Ki-67 has been associated with more aggressive development and a higher risk of re-emergence. It is also helpful for informed decisions on treatment modality.

Nevertheless, the limitations lie in its variability and the lack of standardized measurement methods.

Cell-Free DNA (cfDNA)

The analysis of cfDNA in the bloodstream allows for detecting genetic mutations associated with breast cancer. This non-invasive approach provides valuable information for treatment decisions. Not only have elevated levels of cfDNA been related to advanced cancer, but they have also been proposed as a diagnostic tool for breast cancer and other malignancies.

However, limitations include the potential for false positives and the need for further validation in clinical settings.

The future of breast cancer biomarkers holds promise with ongoing research, technological advancements, and new treatment approaches.

Advancements in technology

Emerging technologies in breast cancer diagnosis and monitoring include advancements in imaging modalities and molecular techniques.

Molecular breast imaging (MBI) and digital breast tomosynthesis (DBT) enhance the precision of detecting abnormalities. Additionally, artificial intelligence (AI) applications are being integrated into diagnostic processes, which aid to analyze mammograms and identify subtle patterns indicative of breast cancer.

Emerging technologies like liquid biopsy and next-generation sequencing also show potential for more accurate and comprehensive biomarker profiling. Integrating these technologies into routine clinical practice could further enhance the early detection and treatment of breast cancer.

Combined biomarker testing

Finally, the potential to combine multiple biomarkers for personalized treatment approaches is also a significant avenue for future research. Utilizing a panel of biomarkers to create a comprehensive profile of a patient’s tumor allows for more knowledge of the disease, and this approach can guide physicians in selecting the most effective combination of therapies tailored to an individual’s unique cancer biology.

Biomarkers have revolutionized the landscape of breast cancer diagnosis and treatment, with testing for the disease nowadays likely to include at least one type of biomarker testing. From improving accuracy and enabling early detection to facilitating personalized medical journeys, these biomarkers play an important role in the fight against breast cancer. The exploration of common breast cancer biomarkers, which include hormone receptor status, HER2, thymidine kinase, CA 15-3 and CA 27.29, Ki67, and cfDNA, highlights the diverse approaches to characterizing the disease.

As we look toward the future, it is essential to continue supporting research and development in breast cancer biomarkers. The potential for emerging technologies and the combination of multiple biomarkers is critical to further advancements in personalized treatment approaches. Collectively, we can contribute to the ongoing progress in breast cancer diagnosis and treatment by fostering collaboration between researchers, clinicians, and industry stakeholders.

Ultimately, the widespread integration of biomarker testing into clinical practice will empower healthcare professionals to make informed decisions, resulting in improved patient outcomes. The DiviTum® TKa test kit is a tool that allows healthcare providers to track patient response throughout treatment, particularly in whether they are responding optimally to CDK4/6 inhibitor therapy. To learn more about the test and methods of procurement, you can contact us.

1. Seale, K. N. and Tkaczuk, K. H. R. “Circulating biomarkers in breast cancer.” Clinical Breast Cancer, 22(3), pp. e319–e331. Published September 22, 2021. https://pubmed.ncbi.nlm.nih.gov/34756687/
2. Autry, J. “Dr. Abenaa Brewster’s pioneering research: Unraveling the potential of blood-based biomarkers in breast cancer.” Susan G. Komen. Published June 26, 2023. https://www.komen.org/blog/dr-abenaa-brewsters-pioneering-research-unraveling-the-potential-of-blood-based-biomarkers-in-breast-cancer
3. “Access to biomarker testing.” American Cancer Society Cancer Action Network. https://www.fightcancer.org/what-we-do/access-biomarker-testing
4. “Biomarkers in Cancer: An Introductory Guide for Advocates.” Research Advocacy Network. https://cancer.wisc.edu/research/wp-content/uploads/2019/05/Biomarkers-in-Cancer.pdf
5. “Breast cancer early detection and diagnosis.” American Cancer Society. https://www.cancer.org/cancer/types/breast-cancer/screening-tests-and-early-detection.html
6. “2021 NCCN Patient Advocacy Summit Policy Report: Advancements in Precision Medicine and Implications for Quality, Accessible, and Equitable Cancer Care.” National Comprehensive Cancer Network. Published 2021. https://www.nccn.org/docs/default-source/oncology-policy-program/pas-policy-report-precision-medicine-final.pdf?sfvrsn=468e4a2b_1
7. “High Sensitvity-HER2 Testing.” Yale School of Medicine. https://medicine.yale.edu/pathology/ypl/services/her2/
8. Slamon, D. J. et al. “Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/ neu oncogene.” Science, 235(4785), pp. 177–182. National Library of Medicine: National Center for Biotechnology Information. Published 1987. https://pubmed.ncbi.nlm.nih.gov/3798106/
9. “High Sensitvity-HER2 Testing.” Yale School of Medicine. https://medicine.yale.edu/pathology/ypl/services/her2/
10. “Thymidine Kinase.” Science Direct. https://www.sciencedirect.com/topics/neuroscience/thymidine-kinase
11. Seale, K. N. and Tkaczuk, K. H. R. “Circulating biomarkers in breast cancer.” Clinical Breast Cancer, 22(3), pp. e319–e331. Published September 22, 2021. https://pubmed.ncbi.nlm.nih.gov/34756687/