CA 15-3

Updated: May 24, 2012

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Reference Range
Cancer antigen 15-3 (CA 15-3) is used to monitor response to breast cancer treatment and disease recurrence. The reference range of serum CA 15-3 is less than 30 U/mL. The upper limit of the range varies depending on the laboratory and kit used for the test. Values obtained with different assay kits, methods, or laboratories cannot be used interchangeably.

Interpretation
CA 15-3 levels are most commonly used to monitor metastatic breast cancer during active therapy. Tumor marker levels must be used in conjunction with the history, physical examination, and diagnostic imaging. A decrease in marker levels during treatment can indicate tumor response, whereas stable or increasing levels despite adequate treatment can indicate that the tumor is not responding to treatment or that the tumor is recurring. CA 15-3 measurement can also be used to survey disease recurrence after treatment of metastatic breast cancer. In the absence of measurable disease, an increase in CA 15-3 levels could indicate treatment failure. However, CA 15-3 levels can rise during the initial 4-6 weeks of starting therapy. This transient rise does not usually correlate with disease progression. Higher CA 15-3 levels have been correlated with more advanced stages of breast cancer [1] or with larger tumor burden. If the tumor produces CA 15-3, marker levels will increase as the tumor grows. The highest levels may be seen in metastatic breast cancer, particularly when metastases to the liver or bones exist. However, CA 15-3 can be low or absent in all of these settings, since not all breast cancers produce CA 15-3 or early-stage breast cancers may not produce detectable CA 15-3 levels. Thus, normal levels do not ensure the absence of localized or metastatic breast cancer. Elevation of CA 15-3 levels can also be seen in healthy individuals, in benign conditions, and in other malignant conditions. However, CA 15-3 levels tend to remain relatively stable over time in benign conditions; thus, elevated levels need to be interpreted within the context o f the patients history and physical examination, diagnostic imaging, and laboratory workup. Benign causes of elevated CA 15-3 levels are as follows:[2] Chronic hepatitis

Liver cirrhosis Tuberculosis Sarcoidosis Benign breast disease Pelvic inflammatory disease Endometriosis Systemic lupus erythematosus Lactation and pregnancy Malignant causes of elevated CA 15-3 levels are as follows: Small cell lung cancer Non-small cell lung cancer Liver cancer Colon cancer Ovarian cancer Endometrial cancer Pancreatic cancer

Collection and Panels

Collection

Specimen: Serum Container: Red-top tube (see the first image below), tiger-top tube (see the second image below), or gold-top tube (see the third image below). Discuss collection methods with your laboratory prior to collecting the

specimen.

Red-top tube.

Red/black-top

tube. Also called tiger-top tube and SST (serum separator tube). tube.

Venous blood collection gold-top (serum separator)

Collection method: Venipuncture

Panels
Serum CA 15-3 is not typically part of a panel. CA 15-3 may also be ordered with other tests such as estrogen receptor, progesterone receptor, HER2/neu, or other genetic expression tests. Consideration may be given to ordering multiple tumor markers due to the heterogeneity in cell composition of each tumor. Other tumor markers for epithelial-derived carcinomas include CEA, CA 19-9, and CA 125.[3] Cancer antigen 27.29 (CA 27.29) measures the same antigen in the blood as CA 15-3. One or the other tumor marker is ordered, typically not both.

Background
Description
Cancer antigen 15-3, or CA 15-3, is an epitope of a large transmembrane glycoprotein named MUC1 that is derived from the MUC1 gene. The MUC1 protein, also known as polymorphic epithelial mucin or epithelial membrane antigen, has a large extracellular region, a transmembrane sequence, and a cytosolic domain. This protein is frequently overexpressed and aberrantly glycosylated on its extracellular region in breast cancer. [4] Physiologically, the MUC1 protein may be involved in cell adhesion by decreasing the degree of cell-toextracellular matrix and cell-to-cell interactions.[4] It has been suggested that the MUC1 protein and its overexpression may be causally related to cancer invasion and metastasis. The CA 15-3 antigen (also known as MUC1, from which it is derived) represents sequences of mucins that are often overexpressed in malignant glandular cells, such as breast cancer. [5] These carbohydrate epitopes may be antigenically different than those in normal breast cells. As tumor cells shed this MUC-1 antigen into the bloodstream, it is recognized by 2 monoclonal antibodies in a radioimmunoassay. These 2 antibodies target epitopes located on the peptide core of the extracellular domain of MUC1. Early-stage breast cancers have a low incidence of elevated CA 15-3 levels, while higher-stage breast cancers have an increased incidence of elevated levels as well as higher absolute levels. However, not all breast cancers express the CA 15-3 antigen, so this assay cannot detect all breast cancers. The MUC-1 protein can also be measured in the peripheral blood by a related test, CA 27.29

Indications/Applications
CA 15-3 testing to screen, diagnose, and stage breast cancer Currently, insufficient data exists to recommend the use of CA 15-3 measurement for screening, diagnosing, or staging breast cancer.[6] CA 15-3 levels are elevated infrequently in early-stage breast cancer or completely absent from other breast cancers, making it difficult to detect early-stage cancers or those tumors that do not express this antigen. However, several studies report prognostic value of the CA 15-3 marker in early-stage

breast cancer.[6, 7] Presence of this tumor marker may predict a worse outcome, but the implication on management of early-stage breast cancer remains unclear. This marker has no clinical value in breast cancers that do not produce the CA 15-3 marker. CA 15-3 levels may also be increased in several benign and malignant conditions. This results in low sensitivity, specificity, and positive predictive values, making it difficult to reliably screen, diagnose, or stage breast cancers. The CA 27.29 assay is slightly more sensitive for breast cancer, but its indications and limitations are identical to the CA 15-3 assay.[6] CA 15-3 testing to detect recurrent disease after treatment of primary breast cancer Currently, insufficient data exists to recommend the use of CA 15-3 testing for monitoring the recurrence of breast cancer after primary and/or adjuvant treatment of a primary breast cancer. Several studies have shown that an increase in CA 15-3 levels may predict recurrence approximately 56 months prior to the onset of signs or symptoms, or positivity of other tests.[6, 8, 9] However, no randomized clinical trials have shown that early detection and treatment of these asymptomatic or occult recurrences improve overall survival, disease-free survival, and quality of life.[6] Additionally, the cost-effectiveness and impact of increased treatment toxicity with early detection is unclear. CA 15-3 testing for clinical management of metastatic breast cancer The overall sensitivity and specificity of CA 15-3 for all breast cancers is low. However, the sensitivity and specificity is higher for advanced (metastatic) or recurrent disease. Studies have shown that CA 15-3 levels may increase in larger tumors and higher-stage breast cancers, which is consistent with its putative role in antiadhesion, cancer cell invasion, and metastases.[4] CA 15-3 testing, in conjunction with the history, physical examination, and diagnostic imaging, can be used to monitor response of metastatic breast cancer to active therapy.[6] CA 15-3 measurement, however, should not be used alone to monitor treatment response in this setting. Additionally, if no other indication of measurable disease exists (ie, via history, physical examination, or imaging), an increase in CA 15-3 levels can represent a failure of treatment. False rises in CA 15-3 levels may occur in the first 4-6 weeks of therapy, and caution should be used when interpreting these results. [6]

Considerations
Breast cancer is one of several conditions that may cause elevated levels of CA 15-3. Elevated levels can be seen in healthy individuals, in benign conditions, and in other malignant conditions. Thus, elevated CA 15-3 levels could be due to conditions other than breast cancer, making interpretation and accurate diagnosis difficult. CA 15-3 levels may be absent or low in early-stage breast cancer, which precludes widespread use of this marker in screening. On the other hand, high levels of CA 15-3 can indicate metastatic disease, but currently insufficient evidence exists to incorporate marker levels into the staging system. Studies have shown that early recurrence of disease can be predicted by an average of 5-6 months prior to other signs or symptoms. However, the benefit of this post-treatment monitoring is controversial since no studies have shown that measurement of this tumor marker leads to more effective therapy and an improvement in patient outcome. Low sensitivity in early-stage breast cancer, low overall specificity, and lack of effective treatment when recurrences are detected are important limitations of the CA 15-3 assay.[10] Prospective, randomized trials will be needed to further clarify the clinical utility and impact on patient outcome of CA 15-3 measurement.

References
1. 2. Swart, R. Medscape: Breast Cancer. Available from: http://emedicine.medscape.com/article/1947145overview. Bon GG et al. Clinical and technical evaluation of ACSBR serum assay of MUC1 gene -derived glycoprotein in breast cancer, and comparison with CA 15-3 assays. Clinical Chemistry. 1997;43(4):585593. Wu, J. Expression of monoclonal antibody-defined tumor markers in four carcinomas. Ann Clin Lab Sci. 1989;19:17-26. Duffy, M., et al. CA 15-3: a prognostic marker in breast cancer. Int J Biol Markers. 2000;15(4):330-3. Klee GG, Schreiber WE. MUC1 gene-derived glycoprotein assays for monitoring breast cancer (CA 153, CA 27.29, BR): are they measuring the same antigen?. Arch Pathol Lab Med. Oct 2004;128(10):1131-5.[Medline].

3. 4. 5.

6.

Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. Nov 20 2007;25(33):5287-312. [Medline]. Ebeling FG, Stieber P, Untch M, Nagel D, Konecny GE, Schmitt UM. Serum CEA and CA 15-3 as prognostic factors in primary breast cancer. Br J Cancer. Apr 22 2002;86(8):1217-22. [Medline]. Kokko R, Holli K, Hakama M. Ca 15-3 in the follow-up of localised breast cancer: a prospective study. Eur J Cancer. Jun 2002;38(9):1189-93. [Medline]. Nicolini A, et al. Intensive post-operative follow-up of breast cancer patients with tumour markers: CEA, TPA or CA15.3 vs MCA and MCA-CA15.3 vs CEA-TPA-CA15.3 panel in the early detection of distant metastases. BMC Cancer. Nov 2006;20(6):269.

7. 8. 9.

10. Sturgeon C. Practice guidelines for tumor marker use in the clinic. Clin Chem. Aug 2002;48(8):11519.[Medline]. 11. Axelrod, D. Hepatocellular Carcinoma Available from: http://emedicine.medscape.com/article/197319overview. 12. Bartels, C. Systemic Lupus Erythematosus. 13. Creasman, W. Endometrial Carcinoma Available from: http://emedicine.medscape.com/article/254083overview. 14. Dragovich, T. Colon Adenocarcinoma Available from: http://emedicine.medscape.com/article/277496overview. 15. Dragovich, T. Pancreatic Cancer Available from: http://emedicine.medscape.com/article/280605overview. 16. Green, A. Ovarian Cancer Available from: http://emedicine.medscape.com/article/255771-overview. 17. Herchline, T. Tuberculosis. Available from: http://emedicine.medscape.com/article/230802-overview. 18. Kamangar, N. Sarcoidosis. Available from: http://emedicine.medscape.com/article/301914-overview. 19. Kapoor, D. Endometriosis. Available from: http://emedicine.medscape.com/article/271899-overview. 20. Shepherd, S. Pelvic Inflammatory Disease. Available from: http://emedicine.medscape.com/article/256448-overview. 21. Tan, W. Small Cell Lung Cancer. Available from: http://emedicine.medscape.com/article/280104overview. 22. Tan, W. Non-Small Cell Lung Cancer. Available from: http://emedicine.medscape.com/article/279960overview. 23. Wagner, C. Human milk and lactation. Available from: http://emedicine.medscape.com/article/1835675overview. 24. Wolf, D. Cirrhosis. Available from: http://emedicine.medscape.com/article/185856-overview.

Question: What is the cancer antigen 15-3 (CA 15-3) blood test for breast cancer? Cancer Antigen 15-3 (CA 15-3) is a blood test that is given during or after treatment for breast cancer. It is most useful in monitoring advanced breast cancer and your response to treatment. CA 15-3 is not a blood test that screens for breast cancer. It is a tumor marker test that is helpful in tracking cancers that overproduce CA 15-3. Answer: About Cancer Antigen 15-3 (CA 15-3) CA 15-3 is a protein that is a normal product of your breast tissue, and it does not cause breast cancer. If a cancerous tumor (cells growing out of control) is present in your breast, though, your levels of CA 15-3 may increase as the number of cancer cells increase. Tumor cells will shed copies of the CA 15-3 protein, which can be measured by this blood test and by a related test of cancer antigen 27.29 (CA 27.29). Should I Have a CA 15-3 Tumor Marker Test? Not every breast tumor causes a rise in CA 15-3, so for patients with tumors that do not produce CA 15-3 or with early-stage breast cancer, this test is not useful. Only about 30% of patients with localized breast cancer (cancer limited to the breast) will have increased levels of CA 15-3. In patients with metastatic breast cancer, CA 15-3 can be found in 50 to 90% of all cases. Reasons to Have a CA 15-3 Tumor Marker Test If you have completed treatment for breast cancer, your doctor may test your blood for CA 15-3 on a regular schedule to see if your levels of this antigen are rising or remaining steady. Rising levels of CA 15-3 may indicate a recurrence of breast cancer, but since other conditions can cause higher levels of this antigen, the test results must be taken in to consideration with the results of imaging studies, your symptoms and other tests forhormone sensitivity, HER2/neu and BRCA genes. Benefits of the CA 15-3 Blood Test Your levels of CA 15-3 will help your doctor determine if:

Your treatment is working or needs adjustment Your cancer has made an early recurrence, without noticeable symptoms Your cancer has progressed You have other conditions

Other Benign Conditions Test High for CA 15-3 Breast cancer is only one condition that may cause high levels of CA 15-3. Pregnancy and lactation also increase your levels of CA 15-3. Several noncancerous conditions (benign breast or ovarian disease, endometriosis, pelvic inflammatory disease and hepatitis) can bring up your levels of CA 15-3.

CA 15-3 and Other Cancers Ovarian, lung and prostate cancers may also produce CA 15-3.
Sources: American Cancer Society. Tumor Markers. What Are Tumor Markers? Revised: 01/04/2006. American Association for Clinical Chemistry. Lab Tests Online. CA 15-3. Last reviewed on June 24, 2006. American Society of Clinical Oncology. ASCO Patient Guide: Tumor Markers for Breast Cancer. Last Updated: October 22, 2007.

Cancer antigen 15-3 (CA15-3)

Why a CA15-3 test is done How a CA15-3 test is done What the results mean What happens if a change or abnormality is found

Cancer antigen 15-3 (CA15-3) is a protein produced by a variety of cells, particularly breast cancer cells. Why a CA15-3 test is done A CA15-3 test may be done to check:

a persons response to treatment for breast cancer o This is the main use of CA15-3 tests. if breast cancer has come back (recurred) after treatment

Back to top How a CA 15-3 test is done A CA15-3 test is usually done in a private laboratory or hospital laboratory. No special preparation is usually needed.

CA15-3 is usually measured by a blood test. The sample is sent to a laboratory to be analyzed by special machines.

Back to top What the results mean An increased CA15-3 value can occur in non-cancerous and cancerous conditions.

non-cancerous conditions o pregnancy o lactation o endometriosis o pelvic inflammatory disease o benign breast or ovarian disease o liver diseases such as cirrhosis or hepatitis cancerous conditions o breast cancer CA15-3 is often increased in advanced breast cancer or when cancer has spread (metastasized). It is rarely increased in women with early stage breast cancer. o lung cancer o ovarian cancer o pancreatic cancer o liver cancer o stomach cancer

In cancerous conditions:

A decrease or return to normal value may mean that the cancer has responded well to treatment. An increase may mean that the cancer is not responding well to treatment, is still growing or is coming back (recurring). o A slight increase may not be significant. The doctor looks at trends in the increase over time.

Back to top What happens if a change or abnormality is found The doctor will decide if more tests, procedures, follow-up care or additional treatment is needed.

References
Cancer information / Diagnosis and treatment / Tests and procedures / Cancer antigen 15-3 (CA 15-3) Tumor Markers. American Association for Clinical Chemistry. (2010, November 24). Lab Tests Online.

CA 15-3. American Association for Clinical Chemistry. (2011, March 22). Lab Tests Online.

American Cancer Society. (2009, 12/21). Tumor Markers. Atlanta: American Cancer Society.

CA15.3. BC Cancer Agency. (2004, January). Cancer Management Guidelines. (Reviewed Edition). Vancouver, BC: BC Cancer Agency.

Fischbach F. & Dunning MB. (2009). Manual of Laboratory and Diagnostic Tests. (8th Edition). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins.

Read more: http://www.cancer.ca/Reference/?cceid=4001#ixzz2mEH75NOx

Test ID: CA153 Cancer Antigen 15-3 (CA 15-3), Serum

Overview Specimen Clinical and Interpretive Performance Fees and Coding
LIS RESOURCES

Setup Information: Excel | PDF

Sample Report Setup Reference Guide

NY State Approved
Yes

Useful For
The management of breast cancer patients when used in conjunction with clinical information and other diagnostic procedures. Serial testing can assist in early detection of disease recurrence in previously treated stage II and III breast cancer patients

Monitoring response to therapy in metastatic breast cancer patients

Method Name
Electrochemiluminescence Immunoassay

Reporting Name
Cancer Ag 15-3, (CA 15-3), S

Aliases
CA 15-3 (Cancer Antigen 15-3) CA153 MUC-1 Mucin-Like Carcinoma-Associated Antigen

Specimen Type
Serum

Specimen Required
Collection Container/Tube:

Preferred: Red top Acceptable: Serum gel Specimen Volume: 0.5 mL

Specimen Minimum Volume

0.45 mL

Reject Due To
Hemolysis Mild OK; Gross reject Lipemia Icterus Other Mild OK; Gross OK NA NA

Specimen Stability Information

Specimen Type Temperature Serum Time Refrigerated (preferred) 7 days Frozen 90 days

Useful For
The management of breast cancer patients when used in conjunction with clinical information and other diagnostic procedures. Serial testing can assist in early detection of disease recurrence in previously treated stage II and III breast cancer patients

Monitoring response to therapy in metastatic breast cancer patients

Clinical Information
Carcinoma of the breast is the most prevalent form of cancer in women. These tumors often produce mucinous antigens that are large molecular weight glycoproteins with O-linked oligosaccharide chains. Tumor-associated antigens encoded by the human MUC-1 gene are known by several names, including MAM6, milk mucin antigen, cancer antigen (CA) 27.29, and CA 15-3.

CA 15-3 assay values are not elevated in most normal individuals and are frequently elevated in sera from breast cancer patients.

Nonmammary malignancies in which elevated CA 15-3 assay values have been reported include: lung, colon, pancreas, primary liver, ovary, cervix, and endometrium.

Reference Values
Males: <30 U/mL (use not defined) Females: <30 U/mL

Interpretation

Increasing and decreasing values show correlation with disease progression and regression, respectively.(1) Increasing cancer antigen 15-3 (CA 15-3) assay values in patients at risk for breast cancer recurrence after primary therapy may be indicative of recurrent disease before it can be detected clinically (2,3) and may be used as an indication that additional tests or procedures should be performed.

Cautions
Testing for cancer antigen 15-3 (CA 15-3) should be performed in conjunction with other clinical methods used for the early detection of recurrence.

Measurement of CA 15-3 is not useful as a cancer-screening test.

Some patients, who have been exposed to mouse antigens, whether in the environment or as part of treatment or imaging procedures, may have circulating antimouse antibodies. These antibodies may interfere with the assay reagents to produce unreliable CA 15-3 assay results

Wait at least 8 hours after the last biotin administration before drawing a specimen from patients receiving therapy with high doses of biotin (ie, >5 mg/day) to avoid assay interference.

In rare cases, interference due to extremely high titers of antibodies to ruthenium or streptavidin can occur.

Clinical Reference
1. Molina R, Zanon G, Filella X, et al: Use of serial carcinoembryonic antigen and CA 15-3 assays in detecting relapses in breast cancer patients. Breast Cancer Res Treat 1995;36:41-48 2. Geraghty JG, Coveney EC, Sherry F, et al: CA 15-3 in patients with locoregional and metastatic breast carcinoma. Cancer 1992;70:2831-2834 3. Kallioniemi OP, Oksa H, Aaran RK, et al: Serum CA 15-3 assay in the diagnosis and follow-up of breast cancer. Br J Cancer 1988;58:213-215

Method Description
The instrument used is the Roche Cobas. The Roche cancer antigen 15-3 (CA 15-3) method is a sandwich electrochemiluminescence immunoassay that employs a biotinylated monoclonal CA 15-3-specific antibody and a monoclonal CA 15-3-specific antibody. CA 15-3 in the automatically prediluted specimen reacts with both the biotinylated monoclonal CA 15-3-specific antibody (mouse) and the monoclonal CA 15-3-specific antibody (mouse) labeled with a ruthenium complex, forming a sandwich complex. Streptavidin-coated microparticles are added and the mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of voltage to the electrode induces the chemiluminescent emission, which is then measured.(Package insert: Roche CA 15-3 reagent, Roche Diagnostic Corp., Indianapolis, IN 2010-09, V14)

Day(s) and Time(s) Test Performed

Monday through Friday; 5 a.m.-12 a.m.

Saturday; 6 a.m.-6 p.m.

Analytic Time
1 day

Maximum Laboratory Time

3 days

Specimen Retention Time

3 months

Performing Laboratory Location

Rochester