Breast Cancer Tumor Marker Tests

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Breast cancer tumor markers are substances that are produced by cancer cells or by the body in response to cancer, and include tests such as CA 15-3, CA 27.29, CEA, CA-125, and circulating tumor cells (CTCs). They can be used to monitor for progression of the cancer, evaluate the response to treatment, or herald a recurrence, and may be able to predict who will have a late recurrence. There are many limitations to these tests, as not all cancers cause an elevation in levels, and when the levels are elevated, it may be due to a condition other than cancer. Tumor marker tests are not used alone to evaluate or plan breast cancer treatment, but may be helpful as an adjunct to other tests such as imaging studies.

Receptor tests such as estrogen receptor and HER2 receptor tests are considered biomarkers, but are used in a different way than tumor marker tests and are discussed elsewhere on this site.

Purpose of Tests

Tumor markers are substances that can be detected in blood or urine when a tumor is present, and are either secreted by a tumor, or by the body in response to a cancer. There are several different types of tumor marker tests used with breast cancer, and these vary in many ways. Some of these tests are used only for people with breast cancer, whereas others may be used for people with a number of different cancers.

Indications for Tests

Breast cancer tumor marker tests may be used for a number of different reasons and in different settings. These include:

  • To screen for cancer (tumor marker tests are not ordinarily used to screen for or diagnose breast cancer, and even if the tests are done, they must be interpreted along with other tests)
  • To see if a cancer is progressing (especially with metastatic breast cancer)
  • To screen for recurrence of a cancer
  • To monitor the response to treatment of a cancer

Tumor Marker Tests for Breast Cancer

There are several tumor marker tests available, with the most commonly used at the current time being CA 15-3 and CA 27.29.

Cancer Antigen 15-3 (CA 15-3)

Cancer Antigen 15-3 (CA 15-3) is a protein produced by breast tissue, including both normal breast cells and cancerous breast cells. CA 15-3 is released into the bloodstream when these cells break down. The test has limitations, in that increased levels are only found in 30 percent of people with early stage and 50 percent to 90 percent of people with metastatic breast cancer. Levels may also be increased due to non breast cancer related conditions such as cirrhosis, lupus, pelvic inflammatory disease, and much more.

It may be used to:

  • Screen for recurrence: Increasing levels may mean a breast cancer has returned.
  • To see if a breast cancer is progressing: Increasing levels may mean that a breast cancer is worsening. Levels tend to be particularly high when women develop bone metastases and liver metastases from breast cancer.
  • To monitor the response to treatment: If levels are decreasing, the treatments used may be working, though there are exceptions (see below under limitations), and levels often take 4 weeks to 6 weeks to decrease when a tumor is decreasing in size.

Cancer Antigen 27.29 (CA 27.29) such TRU-QUANT

Cancer Antigen 27.29 (CA 27.29) is a glycoprotein found on the surface of epithelial cells such as breast cancer cells. Levels may be increased in people with breast cancer, but also with cancers such as lung cancer, colon cancer, and ovarian cancer, as well as benign conditions like ovarian cysts and liver disease.

It may be used:

  • As a supplemental test in diagnosis: While never used alone, it may be used as an added test in making the diagnosis of breast cancer.
  • To monitor for recurrence: Increasing levels of CA 27.29 might mean a recurrence of breast cancer, and levels often begin to increase around 5 months before signs of a recurrence are noted. That said, it's not certain whether detecting a recurrence early can make any difference in long-term survival.
  • To monitor for progression: Increasing levels often mean a cancer is progressing.
  • To evaluate the response to treatment: If a treatment is working, levels often decrease.

In general, the CA 27.29 test provides information that is very similar to the CA 15-3 test, and most of the time, only one of these tests will be ordered.

CA-125

Cancer antigen 125 (CA-125) is more commonly known as the tumor marker often used to monitor ovarian cancer, but may be used as a test to monitor breast cancer as well.

Carcinoembryonic Antigen (CEA)

Carcinoembryonic Antigen (CEA) is another tumor marker that can be used to monitor breast cancer. CEA is present in small amounts on the blood of everyone, but levels can be elevated with a number of different cancers, including those of the breast, colon, pancreas, and more, as well as in several benign conditions. Levels are also increased in people who smoke. One limitation in particular is that levels usually rise in response to chemotherapy, even if the chemotherapy drugs are effective due to the breakdown of cancer cells.

Circulating Tumor Cells (CTCs)

When a cancer is present, some of the cells continually break off and are absorbed into the bloodstream. A test for circulating tumor cells tests for these cells in the blood. The CellSearch test is most often used for people who have metastatic breast cancer, and may have benefit in guiding treatment decisions, such as whether or not to use treatment with a single therapy or not.

Though still investigational, circulating tumor cells may be used down the line to predict who will have a late recurrence of breast cancer. For women who have estrogen receptor positive breast cancer, roughly 50 percent of recurrences occur at least 5 years after the initial diagnosis. Researchers now found that for women who have circulating tumor cells detected on a blood test done 5-years after diagnosis, the chance that the cancer will recur is 21.7 times higher than those who do not have detectable circulating tumor cells. In the future, the test could be used to help answer the question of how long medications such as aromatase inhibitors should be continued and more.

Limitations

There are a number of limitations to tumor marker testing for breast cancer, including false negatives and false positives.

A false positive is a result that indicates there is a problem when one is not present. With a false positive, there is both the risk of overtreating a cancer based on a misleading test, and the consequent anxiety it causes. A false negative occurs when a test is normal, but a cancer is present or growing.

These tests can also be very expensive, and may or may not be covered by insurance.

Some treatments can cause the results of tumor marker tests to be inaccurate. For example, treatment with the drug Afinitor (everolimus) causes the CA 15-3 test results to actually move in the opposite direction of what is happening.

These tests may also not reflect what is actually happening with a cancer, as levels may take several weeks and sometimes up to 3 months (with CA 27.29) to reflect changes in the cancer.

Finally, human error, such as an incorrectly taken specimen or lab error can lead to erroneous results.

Testing

When your oncologist recommends a tumor marker test, she will explain why the test may be helpful, what the results may mean, and will discuss the limitations of the test.

Preparation

There is no specific preparation needed for these tests.

During the Test

Tumor marker tests are done through a simple blood draw, although for those who have had chemotherapy, this is not always so simple. If you have a port or a pic-line, the sample can be taken using these devices.

After the Test

Tumor marker tests take different periods of time before results are available. Ask you doctor when you can expect to hear your results, and if you will hear about them over the phone or if you need to make an appointment.

Interpreting Results

The results of tumor marker tests can't be properly interpreted by looking at the numbers alone without findings from a physical exam and imaging studies, but rather, are one of the pieces that may help doctors know if a breast cancer is growing, decreasing with treatment, or has recurred.

Normal Ranges

The normal ranges for breast cancer tumor markers is as follows:

  • CA !5-3: The normal range is less than 30 units/mL.
  • CA 27.29: The normal range is less than 38 units/mL.
  • CA-25: The normal range is 0 to 35 U/mL
  • CEA: The normal level is less than 2.5 ng/mL in non-smokers and less than 5 ng/mL in people who smoke.
  • Circulating Tumor Cells: In general, the level of circulating tumor cells should be zero if no evidence of cancer is present. In those who have metastatic cancer, the change over time is usually more important than the absolute level.

A Word From Verywell

Breast cancer tumor marker tests may be used as an adjunct to monitor progression or response to treatment, but should never be used alone as a measure to guide treatment. While helpful, there are several limitations to these tests, and for most tests, a number of reasons why the number could be high or low unrelated to breast cancer.

Learning about your cancer and being your own advocate in your care can help you feel more in control of your disease, and sometimes, may even make a difference in outcome. The fact that you are looking at this article means that you are playing an active role in your care. Keep asking questions. The treatment and monitoring of breast cancer is improving rapidly, and it's hard for any one person, even a breast cancer oncologist, to stay on top of every change. As a survivor, nobody is more motivated than you to make sure you receive the best and most up-to-date care possible.

Sources:

Bast, R., Croce, C., Hait, W. et al. Holland-Frei Cancer Medicine. Wiley Blackwell, 2017.

Davis, A., Pierga, J., Dirix, L. et al. The Impact of Circulating Tumor Cells (CTCs) Detection in Metastatic Breast Cancer (MBC): Implications of "Indolent" Stage IV Disease. Journal of Clinical Oncology. 2018. 36(15_Suppl):1019.

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