Uncovering the Important Role of CA15-3 in Predicting Distant Metastasis of Breast Cancer

CA15-3 represents a tumor marker derived from a soluble part of the MUC1 glycoprotein antigen and served initially to monitor serum levels in breast cancer patients. CA15-3 functions as one of the primary tumor markers for breast cancer investigations particularly regarding distant metastasis surveillance. While CA15-3 lacks specificity as a diagnostic tool for breast cancer it proves essential for monitoring disease progression and treatment response along with providing warnings for potential recurrence.

• Molecular source: MUC1 represents a transmembrane glycoprotein found on the surfaces of many epithelial cells throughout the body. Breast cancer cells exhibit overexpression of this protein while simultaneously secreting it into the bloodstream.
• Detection method: The levels of CA15-3 in serum serve as a measurement for monitoring disease status.
• Normal range: The standard reference value for this measurement typically stands below 30 U/mL although laboratories may report slight variations.

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Harm of Breast Cancer to Women

Tumor growth can cause pain, lumps, nipple discharge or skin deformation. In the late stage, distant metastases such as bones, lungs, liver, and brain may occur, leading to organ failure. Chemotherapy, radiotherapy, surgery, and hormone therapy in the treatment of breast cancer can cause hair loss, nausea, decreased immunity, menstrual disorders, or early menopause. Some patients experience lymphedema or limited motor function.

Important Role of CA15-3

CA15-3 is a fragment released into the blood by MUC1 glycoprotein, which is mainly secreted by breast cancer cells. It can be quantitatively analyzed by serum testing.

Function of Source Protein MUC1

CA15-3 is derived from the exocytic fragment of MUC1 protein. In normal epithelial cells, MUC1 can prevent pathogen attachment and protect the epithelial barrier. The intracellular structure of MUC1 can participate in the signaling pathways of cell proliferation, apoptosis and differentiation. The glycosylation form of MUC1 can regulate immune recognition and affect tumor immune escape.

Role in Tumors

In tumors such as breast cancer, the MUC1 structure mutates and the glycosylation is abnormal, which promotes the adhesion, invasion and metastasis of tumor cells.

The Important Role of CA15-3 in Predicting Distant Metastasis of Breast Cancer

Monitoring Distant Metastasis

During the metastasis of breast cancer, CA15-3 levels often increase significantly, especially in common metastatic sites such as bones, liver, and lungs. Continuously elevated CA15-3 indicates the possible presence of occult distant metastasis, that is, imaging has not yet found, but biochemical changes have occurred. Many studies have shown that the increase in CA15-3 may be earlier than the clinical or imaging findings of metastatic lesions, which is expected to achieve early intervention.

Evaluating Treatment Response

During systemic treatment (such as chemotherapy, endocrine therapy, targeted therapy), a decrease in CA15-3 levels often indicates that the treatment is effective. If CA15-3 levels continue to increase, it may indicate drug resistance, disease progression, or the formation of new metastatic lesions.

Predicting the Risk of Recurrence

For patients with early breast cancer, regular monitoring of CA15-3 after surgery can help predict recurrence, especially the risk of distant metastasis. CA15-3 levels may have begun to increase several months before recurrence, which provides a window period for early intervention.

Combined with Other Markers to Improve Prediction Accuracy

CA15-3 is often used in combination with CEA (carcinoembryonic antigen), CA27.29, etc. to improve sensitivity and specificity. Combined marker monitoring is particularly important in patients with HER2-positive or triple-negative breast cancer.

Sensitivity and Specificity of CA15-3

Limitations of CA15-3

• Non-specific elevation: Liver cirrhosis and cancers of the ovary and lung can lead to increased CA15-3 levels.
• No expression in some breast cancer patients: Not all breast cancer patients will have elevated CA15-3, especially in the early stages.
• Cannot replace imaging examinations: should be used in conjunction with CT, PET/CT, bone scans, etc.

CA15-3 has important value in predicting distant metastasis of breast cancer, especially in monitoring disease progression and recurrence, providing strong support for individualized treatment. However, its limitations should be noted, and it needs to be combined with other means for comprehensive analysis. Regular physical examinations, imaging examinations, and tumor marker monitoring (such as CA15-3) when necessary are particularly important for high-risk women.

References

1. Hayes, D., et al. Comparison of circulating CA15-3 and carcinoembryonic antigen levels in patients with breast cancer. Journal of Clinical Oncology. 1986, 4(10): 1542-1550.
2. Li, J., et al. Tumor markers CA15-3, CA125, CEA and breast cancer survival by molecular subtype: a cohort study. Breast Cancer. 2020, 27: 621-630.