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Monitoring Breast Cancer Progression with Tumor Markers

Monitoring Breast Cancer Progression with Tumor Markers

Breast cancer is one of the most diagnosed cancers in the European Union, with an estimated 380,000 cases annually, constituting approximately 13.8% of all cancer diagnoses*. Breast cancer is much more common in women, with 99% of cases affecting women, but they can nevertheless occur in men.

The cancer is divided into stages and grades based on tumor size, the tumor’s involvement in nearby lymph nodes, and the presence of metastasis. Stages range from 0 to IV, with IV being the most severe. Cancer grades range from I to III based on the appearance of cancer cells, with grade III indicating high levels of abnormality and aggressiveness of the tumor.

While stage IV breast cancer (also known as metastatic or advanced-stage breast cancer) is incurable, it can be managed with different treatment approaches aimed at controlling the disease. With the right treatment dosage and type administered, patients may be able to prolong their survival and ease the severity of side effects from the cancer and related therapies.

In this article, we look at how blood-based tumor marker tests play a role in stage IV breast cancer management. Particularly, the types of markers available, their functions and limitations, and their clinical applications.

Blood-based biomarkers are substances that can be detected in the blood. They are produced by breast cancer cells or normal cells in response to breast cancer. These markers include proteins, enzymes, or genetic material, and their levels of activity in the cancer patient’s blood can provide valuable information on the progression of the disease and their responses to treatment.

This information is used by medical practitioners to tailor treatment journeys for patients, including switching out certain methods in favor of others, or changing the dosage and frequency of medication and therapies for better treatment outcomes.

A big advantage blood-based tumor marker testing plays in disease monitoring is its convenience and minimally invasive nature. Testing involves drawing a blood sample from the patient and can be incorporated as part of routine check-ups. Compared to traditional monitoring methods, such as imaging techniques or tissue biopsies, it significantly reduces patient discomfort and risk.

Common blood-based tumor markers

Established and emerging clinical data support the use of several blood-based tumor markers for breast cancer response monitoring.

CA 15-3

This is a blood-based tumor marker frequently used in advanced-stage or metastatic breast cancer monitoring, particularly in the areas of disease progression and treatment response. CA 15-3 is a glycoprotein that is produced by breast cancer cells, and measuring its levels in the blood of patients over time can provide insights into changes in tumor burden and response to therapy.

However, CA 15-3 has its limitations, such as its lack of specificity and variable sensitivity.

While CA 15-3 levels can be elevated in the blood of breast cancer patients, they may also be elevated in other non-cancerous conditions, such as liver disease, benign breast conditions, and other types of cancer. The lack of specificity can result in an inaccurate assessment of disease progression.

Additionally, while CA 15-3 is suited as a tumor marker for advanced-stage breast cancer, it is not suited for testing in patients with early-stage or localized cancers. When used in early-stage testing, false-negative results may occur when the marker fails to detect the presence of cancer or changes and developments in disease status.

CA 27.29

CA 27.29 is another blood-based tumor marker used in breast cancer monitoring. As a variant of the CA 15-3 protein, CA 27.29 is particularly useful in monitoring patient response to therapy and detecting disease recurrence in patients with advanced-stage breast cancer.

This is due to the marker’s increased sensitivity in cases where there is extensive tumor burden or metastatic spread. CA 27.29 levels also tend to correlate with more aggressive breast cancer subtypes, such as those involving hormone receptor-positive and HER2-negative tumors.

However, CA 27.29 has its own limitations. Like CA 15-3, CA 27.29 lacks specificity and can be elevated in other non-cancerous conditions, including benign breast conditions, and its sensitivity variability can lead to false-negative results as well when it fails to detect changes in cancer status.


Thymidine Kinase 1 (TK1) is a promising blood-based tumor marker for breast cancer monitoring. As an enzyme involved in DNA synthesis and cell proliferation, measuring TK1 activity levels in the blood can provide valuable insights into cancer cell behavior and tumor aggressiveness.

Elevated levels of TK1 have been observed in the blood of breast cancer patients. This is because as cancer cells divide and proliferate, they require increased DNA synthesis, a process in which TK1 plays a key role.

With serial measurement of TK1 levels over time, changes in tumor burden and patient responses to therapy can be uncovered. Elevated TK1 levels can indicate an aggressive tumor and a poor response to treatment, while decreasing TK1 levels may suggest a positive response.

TK1’s limitation lies in its status as an emerging biomarker. As the enzyme is still being evaluated, further research is required to fully establish its clinical utility and standardize its use in breast cancer monitoring.

Nevertheless, it shows good potential in providing valuable information on cancer cell activity. When used in combination with other assessments and imaging techniques, it is likely to enhance the accuracy and reliability of disease monitoring.

Selecting the most suitable tumor marker for disease monitoring

Among the three blood-based tumor markers introduced, CA 15-3 and CA 27.29 are more commonly used in breast cancer monitoring. This is due to the extensive research published on their clinical utility. However, while TK1 is an emerging tumor marker, its association with cell proliferation has shown promise in disease progression and treatment response monitoring.

Ultimately, the choice of which tumor marker to use may depend on factors such as the specific clinical context, the stage and subtype of breast cancer to be monitored, and the availability of testing. Individual patient characteristics must also be considered. If you would like to determine the most suitable approach for your situation, you should consult with healthcare professionals.