CA 27-29

Cancer antigen 27-29 (CA 27-29) is used to predict early recurrence of disease in women with treated carcinoma of the breast.

The reference range of serum CA 27-29 is less than 38 U/mL. The upper limit of the range may vary depending on the laboratory and testing kit used for the test. Values obtained with different assay kits, methods, or laboratories cannot be used interchangeably.

Elevated CA 27-29 levels can be seen in healthy individuals, in benign conditions, and in other malignant conditions (see below). ^[1] CA 27-29 levels tend to remain relatively stable over time in benign conditions. Thus, an elevated level needs to be interpreted within the context of the patient’s history, physical examination, diagnostic imaging, and laboratory workup findings.

Benign causes of elevated CA 27-29 levels are as follows:

• Chronic hepatitis

• Liver cirrhosis

• Tuberculosis

• Sarcoidosis

• Benign breast disease

• Pelvic inflammatory disease ^[2]

• Endometriosis

• Ovarian cysts

• Systemic lupus erythematosus ^[3]

• Lactation and pregnancy

Malignant causes of elevated CA 27-29 levels are as follows:

• Breast cancer

• Small cell lung cancer

• Non-small cell lung cancer

• Liver cancer

• Colon cancer

• Gastric cancer

• Ovarian cancer

• Uterine cancer

• Endometrial cancer

• Prostate cancer

• Pancreatic cancer

Generally, the higher the CA 27-29 level, the more advanced the breast cancer or larger the tumor burden. ^[4] If the tumor produces CA 27-29, then tumor marker levels tend to increase as the tumor grows. The highest levels may be seen in metastatic breast cancer, particularly with metastases to the liver or the bones. However, CA 27-29 can be low or absent in all of these settings since not all breast cancers produce CA 27-29, or it may be too early in the disease process to detect CA 27-29 levels. Normal levels, therefore, do not ensure absence of localized or metastatic disease.

CA 27-29 levels, in conjunction with the history, physical examination, and diagnostic imaging findings, are typically used to monitor treatment response of metastatic breast cancer. A decrease in CA 27-29 levels can indicate tumor response or regression of disease. Stable or increasing CA 27-29 levels, despite adequate treatment, can indicate tumor nonresponsiveness or tumor recurrence.

CA 27-29 levels can also be serially obtained after treatment of metastatic breast cancer. In the absence of measurable disease, an increase in CA 27-29 levels could indicate treatment failure. A transient rise in CA 27-29 levels can occur during the first 4-6 weeks of starting therapy; ^[5] however, this does not usually correlate with disease progression and should be interpreted with caution.

 

Collection

Collection details are as follows:

• 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

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  Tiger top tube

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  Gold top tube

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• Collection method: Venipuncture

Panels

Panel details are as follows:

• Serum CA 27-29 is not part of a panel.

• CA 27-29 measurement may also be ordered with estrogen receptor, progesterone receptor, HER2/neu, or other genetic expression tests.

• Consideration may be given to ordering multiple tumor markers because of the heterogeneity in cell composition of each tumor. Other tumor markers to follow breast cancer include CEA, CA 15-3, HER2 extracellular domain, and CA 125. ^[6]

• CA 27-29 measures an overlapping antigen as the cancer antigen 15-3 (CA 15-3) assay. One or the other tumor marker is ordered, typically not both.

Description

Cancer antigen 27-29 (or CA 27-29) is an epitope of a large transmembrane mucin glycoprotein named MUC1 that is expressed on the cell surfaces of most glandular epithelia. ^[1] This protein, also known as polymorphic epithelial mucin or epithelial membrane antigen, has a large extracellular region, a transmembrane sequence, and a cytosolic domain. CA 27-29 represents a sequence of mucins on the extracellular region of this glycoprotein.

Physiologically, the MUC1 protein may be involved in protection, lubrication, and cell adhesion by decreasing the degree of cell to extra-cellular matrix and cell to cell interactions. ^{[1, 7]} The MUC1 protein and its overexpression may be causally related to cancer invasion and metastasis.

The MUC1 protein is often overexpressed and aberrantly glycosylated on its extracellular surface in malignant granular cells. ^{[7, 8]} In fact, the carbohydrate epitopes on MUC1 in breast cancer cells may be antigenically different than those in normal breast. As tumor cells shed the MUC1 protein into the bloodstream, CA 27-29 is recognized by a single monoclonal antibody, which recognizes a 20 amino-acid sequence in the mucin core. ^[1] This is in contrast to the CA 15-3 assay, which utilizes two monoclonal antibodies. However, there is overlap, in part, with the epitopes that are recognized by both assays. ^[1] Early stage breast cancers have a low incidence of elevated CA 27-29 and lower absolute levels, while higher-stage breast cancers have a higher incidence of elevated levels and higher absolute levels. Since all breast cancers do not express the CA 27-29 antigen, this assay cannot detect all breast cancers.

The CA 15-3 assay can be used instead of the CA 27-29 assay. Although CA 27-29 may be more sensitive for breast cancer, its indications and limitations parallel those of CA 15-3. ^[5]

Indications/Applications

A study by Jeong et al found chemiluminescence immunoassay to be the most common immunologic technique used for the detection of CA 27-29. In contrast, the detection of CA 15-3 and carcinoembryonic antigen (CEA) were most frequently detected through enzyme-linked immunosorbent assay (ELISA), with electroluminescence and chemiluminescence immunoassays being the second and third most common immunologic techniques used, respectively. ^[9]

CA 27-29 for screening, diagnosing, or staging breast cancer

Data is currently insufficient to recommend the use of CA 27-29 for screening, diagnosing, or staging breast cancer. ^{[5, 10, 11, 12]} CA 27-29 is infrequently elevated in early stage breast cancers or is completely absent from other breast cancers, making it difficult to detect early stage cancers or those tumors that do not express this antigen. Interestingly, the presence of this tumor marker in early stage breast cancer may predict worse outcomes, ^[5] but its implication on management of early stage breast cancers remains unclear. On the other hand, high levels of CA 27-29 can indicate metastatic disease, but evidence is insufficient to incorporate these marker levels into the staging system. Furthermore, since both benign and malignant conditions other than breast cancer can cause elevation in marker levels, this assay cannot be reliably used to screen or diagnose breast cancer.

CA 27-29 for detection of recurrent disease after treatment of primary breast cancer

Currently, data are insufficient to recommend the use of CA 27-29 to monitor recurrence of breast cancer after primary and/or adjuvant treatment of a primary breast cancer. Several studies have shown that an increase in CA 27-29 may predict recurrence approximately 5-6 months prior to the onset of signs/symptoms or positivity of other tests. ^{[5, 13, 14]} However, no randomized clinical trials show that early detection and treatment of these asymptomatic recurrences improve overall survival, disease-free survival, and quality of life. ^[5]

Moreover, using results from the SUCCESS-A breast cancer trial, Hepp et al advised that increased CA 27-29 levels be interpreted cautiously in patients who undergo treatment with granulocyte colony-stimulating factor (G-CSF) during adjuvant chemotherapy, finding that patients who received G-CSF demonstrated a significantly greater rise in CA 27-29 levels than did individuals to whom G-CSF was not administered. ^[15]

CA 27-29 for clinical management of metastatic breast cancer

The overall sensitivity and specificity of CA 27-29 is low when this assay is used in all patients. However, sensitivity and specificity are considerably higher in advanced (metastatic) or recurrent disease. CA 27-29 levels may increase in higher-stage breast cancers and larger tumors, which is consistent with its putative role in anti-adhesion, cancer cell invasion, and metastases. ^[7]

CA 27-29 can be used in conjunction with the history, physical examination, and diagnostic imaging to monitor therapeutic response of metastatic breast cancer. CA 27-29, however, should not be used alone to monitor treatment response in this setting. Additionally, if no other indication of measurable disease (ie, by history, physical exam, or imaging) are present, an elevation in CA 27-29 can otherwise signify treatment failure. However, false rises in CA 27-29 may occur in the first 4-6 weeks of therapy, and caution should be used when interpreting these results. ^[5]

Considerations

Breast cancer is one of several conditions that may cause elevated levels of CA 27-29, and not all breast cancers cause an elevation in marker levels. Thus, a rise in CA 27-29 levels could be due to conditions other than breast cancer, making screening and diagnosis difficult.

Early stage breast cancers have a low incidence of CA 27-29, which confers a low sensitivity in this population of patients. Although high levels of CA 27-29 can indicate metastatic disease, evidence is currently insufficient to incorporate CA 27-29 levels into the staging system.

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 detection of early recurrence leads to more effective therapy and an improvement in patient outcome. The cost-effectiveness of early treatment and its impact on toxicity also remain unknown.

Low sensitivity in early stage breast cancer, low overall specificity, and lack of effective treatment for recurrences are important limitations of the CA 27-29 assay. ^[16] Prospective, randomized trials will be needed to further clarify the clinical utility and impact on patient outcome of CA 27-29.