Cancer associated antigen 549 (CA 549) test

CA 549 Overview

Cancer Associated Antigen 549 (CA 549) is a tumor marker primarily associated with breast cancer. It belongs to the family of high-molecular-weight mucin glycoproteins, similar to other breast cancer markers like CA 15-3.

The CA 549 test measures the level of this antigen in the blood (serum). Its main clinical application is in monitoring patients already diagnosed with breast cancer, particularly for assessing treatment response and detecting disease recurrence or progression, especially in the metastatic setting.

Biology of CA 549

CA 549 is identified as a mucin-like glycoprotein with a large molecular weight, estimated to be around 400,000-500,000 Daltons (400-500 kDa). Like CA 15-3 and CA 27.29, CA 549 detects epitopes (antigenic sites) on the MUC1 protein.

MUC1 is a transmembrane protein normally found on the apical surface of many glandular epithelial cells, including breast ductal cells. In breast cancer cells, MUC1 is often overexpressed, has altered glycosylation patterns (different sugar chains attached), and loses its typical polarized location, leading to increased shedding of MUC1 fragments (including the epitopes detected by the CA 549 assay) into the bloodstream.

Clinical Indications for CA 549 Testing

The primary indication for the CA 549 test is:

• Monitoring diagnosed breast carcinoma: Tracking changes in CA 549 levels over time can help assess the effectiveness of treatment (surgery, chemotherapy, hormonal therapy, radiation) and provide early warning of disease recurrence or progression, particularly in patients with metastatic breast cancer.

CA 549 is not recommended for screening asymptomatic women for breast cancer or for making the initial diagnosis of breast cancer, due to its insufficient sensitivity and specificity.

Interpretation of CA 549 Levels

Results should always be interpreted alongside clinical evaluation, imaging studies, and potentially other tumor markers.

• Normal Range: The upper limit of the normal range for CA 549 is typically considered to be < 11 U/mL (Units per milliliter). However, this threshold can vary slightly based on the specific laboratory and assay method used. Always refer to the reporting laboratory's reference range.
• Elevated Levels in Breast Cancer:
  • Elevated levels are most frequently seen in patients with advanced or metastatic breast cancer. Sensitivity is generally low in early-stage disease.
  • The degree of elevation often correlates with the extent of disease (tumor burden).
  • Serial measurements are key: A significant rise suggests disease progression or recurrence, while a significant fall suggests response to therapy.

Factors Affecting CA 549 Levels

Elevated CA 549 levels are not exclusive to breast cancer:

• Other Malignancies: Elevations can sometimes occur in other cancers, such as ovarian, lung, prostate, or colorectal cancer, usually in advanced stages.
• Benign Conditions: Mild to moderate elevations can be observed in some non-malignant conditions:
  • Benign liver diseases (e.g., cirrhosis, hepatitis - reported in up to 30% of cases).
  • Benign breast conditions (mastopathies - occasionally).
  • Benign ovarian cysts or conditions.
  • Kidney failure.
• Pregnancy: Levels can increase during pregnancy.

Limitations & Relationship to Other Markers

• Specificity: Not specific to breast cancer; can be elevated in other cancers and benign conditions.
• Sensitivity: Often normal in early-stage breast cancer. Not all metastatic breast cancers lead to elevated levels.
• Comparison to CA 15-3 / CA 27.29: CA 549 measures epitopes on the same MUC1 protein as CA 15-3 and CA 27.29. While using different antibodies, their clinical performance characteristics are generally considered very similar. In terms of "information content" for monitoring breast cancer, CA 549 is typically not significantly different from CA 15-3 or CA 27.29. Measuring multiple MUC1-based markers simultaneously (e.g., CA 549 + CA 15-3) is generally not recommended as it usually does not add significant diagnostic or monitoring value.
• Monitoring Focus: Best used for serial monitoring in diagnosed patients with initially elevated levels.

The CA 549 Blood Test Procedure

• Sample Type: Blood serum.
• Preparation: No special patient preparation (e.g., fasting) is usually required.
• Collection: Standard venipuncture (blood draw from a vein).
• Analysis: Measured using specific immunoassays in a clinical laboratory.

References

1. Duffy, M. J. (2006). Serum tumor markers in breast cancer: are they of clinical value? *Clinical Chemistry*, 52(3), 345–351. https://doi.org/10.1373/clinchem.2005.061417 (Discusses various breast cancer markers including MUC1 antigens)
2. National Cancer Institute (NCI). (n.d.). Tumor Markers. Retrieved from https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet
3. American Society of Clinical Oncology (ASCO). (2015). Use of Biomarkers to Guide Decisions on Systemic Therapy for Women With Metastatic Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. *Journal of Clinical Oncology*, 33(27), 3057–3062. https://doi.org/10.1200/JCO.2015.61.1459 (While focusing on therapy decisions, it references the role of markers like CA 15-3/27.29)
4. Klee, G. G., & Schreiber, W. E. (2004). MUC1 antigen assays (CA 15-3, CA 27.29, and BR) in breast cancer. *Mayo Clinic Proceedings*, 79(2), 199–202. https://doi.org/10.4065/79.2.199 (Discusses related MUC1 markers)