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The CA 15-3 Cancer Marker Test And Its Accuracy

Women who have been through treatments for breast cancer are normally followed for five years to monitor their status and one of the tests frequently done by doctors is the CA 15-3 marker test. In this article I will share some information about the CA 15-3 test, discuss the accuracy of the test, and some new research.

What Is The CA 15-3 Cancer Marker Test?

CA 15-3 stands for cancer antigen 15-3 which is a protein produced by normal breast cells.  Some  people – not all – with cancerous breast tumors have an increased production of CA 15-3.  The protein does not cause or promote cancer, rather copies of it are cast off by tumor cells, the copies then enter the bloodstream and can be detected through a blood sample.

CA 15-3 Not That Reliable For Early Stage Breast Cancer

The problem with the CA 15-3 test is that it is not all that reliable, particularly for early breast cancer.  One source indicated that CA 15-3 is elevated in only about 10% of women with early localized breast cancer, while another source indicated the figure was 30%.  CA 15-3 levels can also be completely absent in early-stage breast cancer, making it quite difficult to rely upon this test for early stage cancers or those tumors that do not express the antigen.

A 1999 Italian study comparing the CA 15-3 test with another marker test, the CA 27-29, found that “CA27.29 discriminates primary breast cancer from healthy subjects better than CA15.3, especially in patients with limited disease.” ¹

Other Conditions Can Cause Elevated CA 15-3 Levels

CA 15-3 levels can also be elevated in healthy people, as well as in people with other cancers such as lung, pancreas, colon, ovary, or prostate.  Elevated levels are also seen in benign breast disease, cirrhosis, hepatitis, tuberculosis, pelvic inflammatory disease, endometriosis – and this is by no means an exhaustive list.

CA 15-3 More Useful In Metastatic Breast Cancer, Response To Treatment

For those with metastatic breast cancer, the CA 15-3 test does tend to be a bit more reliable an indicator, being elevated in 50-90% of those with breast cancer that has spread to other parts of the body, particularly when metastases to the bones or liver exist.  One French study ² found that 42% of women with metastases present had normal CA 15-3 levels, however.

The CA 15-3 test tends to be most useful for deciding whether a certain treatment is assisting the patient or not, as a decrease in CA 15-3 levels during treatment such as chemotherapy tells the doctor that the tumor is responding to the treatment, while a stable or increasing marker level may indicate that the tumor has not responded as well (or at all) to the treatment.

While it can be worrisome to the patient to be monitored for CA 15-3 – especially if the marker keeps rising over a period of time and various other tests have not picked up cancer activity – it can be a sign for the patient to be more proactive with their anti-cancer regimen rather than waiting for the development of physical symptoms.  Knowing levels are rising early on can have a huge impact on therapies chosen and survival.

New Study Indicates A Combo Of Marker Tests More Specific

A March 2015 study ³ indicated that a combination of 3 marker tests was more useful.  204 disease-free breast cancer patients who had undergone mastectomy were followed and monitored for an average of 3.7 years with a combination of three marker tests.  Researchers employed the CA 15-3, one called TPA (for tissue polypeptide antigen, more on that below), and one called CEA (for carcinoembryonic antigen, more on that below).  This study indicated that “the sensitivity of the CEA-TPA-CA15.3 tumor marker panel was 93%, the specificity was 97.6% and the rate of false ‘warning signals’ per year of follow-up was 9 per 100 patients.”

In addition to the above study, another smaller but interesting Iraqi study on women with breast cancer indicated that tissue polypeptide antigen (TPA) levels were a good indicator of disease progression, as well as tumor response. ⁴

The carcinoembryonic antigen test (CEA) was studied in patients with metastatic colorectal cancer treated with chemotherapy.  The researchers reported that low levels of CEA were indicative of progression-free survival. ⁵

Obviously, new marker tests are being discovered and researched.  A study yet to be published in the Journal of Proteomics ⁶ reported that there was a necessity for the identification of new markers for breast cancer that could lead to early detection and also provide evidence of effective treatment.  The researchers examined 1,020 polypeptides and discovered 78 that were overexpressed in all cancer lines. This kind of forward-thinking research may help us to discover new and better ways of identifying earlier the existence of breast cancer as well as response to treatments.

In the meantime, and to sum up, please be aware that a CA 15-3 tumor marker test on its own does not provide enough information to screen for the presence of breast cancer.  Normal levels do not ensure the absence of localized or metastatic breast cancer, further tests should be employed.

2017 Update: See also my article The Telomerase Test for Monitoring Breast Cancer.

References:

http://breastcancer.about.com/od/tumormarkers/f/ca_15-3.htm

http://emedicine.medscape.com/article/2087491-overview#aw2aab6b3

1.  Comparison of the Diagnostic Accuracy of CA27.29 and CA15.3 in Primary Breast Cancer – http://www.clinchem.org/content/45/5/630.short

2.  Value of CA 15-3 determination in the initial management of breast cancer patients – http://annonc.oxfordjournals.org/content/20/5/962.2.full

3.  An individual reference limit for ‘early’ diagnosis of metastatic breast cancer during postoperative follow-up – http://www.ncbi.nlm.nih.gov/pubmed/25808435

4. Tissue polypeptide antigen & interleukin-6: Are their serum levels a predictor for response to chemotherapy in breast cancer? – http://www.ncbi.nlm.nih.gov/pubmed/25225536

5.  The Association of Serum Carcinoembryonic Antigen, Carbohydrate Antigen 19-9, Thymidine Kinase, and Tissue Polypeptide Specific Antigen with Outcomes of Patients with Metastatic Colorectal Cancer Treated with Bevacizumab: a Retrospective Study – http://www.ncbi.nlm.nih.gov/pubmed/25875421

6.  Determination of the protein expression profiles of breast cancer cell lines by quantitative proteomics using iTRAQ labelling and tandem mass spectrometry – http://www.ncbi.nlm.nih.gov/pubmed/25918110

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