Tumor markers, sometimes known as cancer markers, are biological substances found in the human body. They are often made by cancer cells or by normal cells in response to cancer, and common examples of biomarkers are proteins that certain cells make in larger amounts than normal cells do, or genetic changes found in or appear in the body because of tumor cells.
Tumor markers can be found in body fluids, such as in the blood or in urine. They may also be found in tumor cells, which can be isolated and examined through a biopsy. As they can provide valuable information on the health status of an individual, tumor marker tests are often used to monitor the rate at which cancer grows and develops. Tracking tumor marker presence, activity, and absence can thus provide information on how fast the disease is developing, the type of targeted treatment that may help, the efficacy of treatment, and the potential recurrence of cancer post-treatment.
While not all cancers have tumor markers, or they do not have markers that have been clinically validated, metastatic breast cancer patients do, and patients can undergo tumor marker testing as part of disease monitoring and management.
Metastatic breast cancer (mBC) is the final stage (stage 4) of breast cancer, when cancer cells have undergone metastasis and spread beyond the breast and lymph nodes to other parts of the body, such as to organs like the liver, the brain, or lungs.
In the United States, it is estimated that there are more than 168,000 women living with mBC in 2020. While men can also get mBC, it is much rarer. The survivorship of mBC patients is not high, with one in three patients diagnosed with the disease living five years after the diagnosis. In some rarer cases, mBC patients may live ten or more years beyond diagnosis.
Metastatic breast cancer is also known as advanced breast cancer in Europe.
Typically, metastatic breast cancer patients undergo different drug therapies to shrink the tumors and prolong one's lifespan. However, tumors can become resistant to administered drug therapies over time. This is where tumor markers can come in.
In some cases, blood tests for tumor markers are performed to monitor mBC to see if the cancer is responding to treatment. These are also called liquid biopsies, as these tumor markers are found in bodily fluids such as the blood.
CA 15-3 and carcinoembryonic antigen (CEA) are the most relevant tumor markers in breast cancer. Studies have found a correlation between the presence of these markers and tumor size and nodal involvement in breast cancer patients during metastatic disease progression. Specifically, there were significantly higher concentrations of CA 15-3 and CEA in patients with larger tumors or in breast cancer patients with nodal involvement, rendering them useful for monitoring and managing mBC disease development.
Additionally, a newer, potential mBC tumor marker, Thymidine Kinase 1, have emerged in recent years. Patients with mBC are either on endocrine therapy (ET) for many years or progress quickly. Studies have shown that serum TK activity (TKa) can provide information on cell proliferation—specifically cancer cell proliferation—and is an upcoming, potential tumor marker for monitoring ET and predicting mBC outcome.
The benefits of liquid biopsies—particularly blood-based diagnostics—used as mBC monitoring tools are manifold. Clinicians can perform serial testing and measurements in a relatively non-invasive manner, often through regular blood draws as an alternative to surgical biopsies, and these blood-based tumor markers have the potential to provide immense insight into the biology of the cancer. This can guide treatment options and therapy selection, which can eliminate unnecessary medication and side effects for patients with mBC.
Real-time monitoring of the disease is also available from liquid biopsies. Tumor status can be determined and tracked consistently and frequently, and there is a level of reliability of the information provided from well-researched biomarkers, such as CA 15-3.
Nevertheless, while tumor marker testing is a valuable tool for those with breast cancer, it is also important to remember that not all tumor presence or activity is related to cancer. There are other conditions and diseases that can cause high levels of certain tumor markers. Additionally, there are cancer patients who do not produce the expected levels of tumor markers commonly found in their type of disease.
Clinicians therefore supplement tumor marker testing with other forms of screening and monitoring, such as performing regular scans, examining a patient's bloodwork, and performing biopsies to extract and analyze tissue cells.
And while liquid biopsies are an emerging monitoring tool for metastatic breast cancer patients and offer promise in analyzing biomarkers in blood, there are certain limitations: such as the lack of standardized assays and the need for further validation. As a result, more research is necessary to fully understand each marker's clinical utility.