Mucins are large and complex glycoproteins that are expressed by several epithelial tissues. Mucins have been grouped into 7 distinct families, MUC-1 though MUC-7, based on their genetic and biochemical characteristics. MUC-1 mucins are expressed at the luminal surface of glandular cells. In malignant cells, this mucin is over-expressed and increased amounts are shed into the circulation. Monoclonal antibodies that recognize distinct epitopes on this molecule have been used to develop immunoassays that quantitate MUC-1 mucin levels in serum. Clinically, these immunoassays have been used to monitor breast cancer recurrence. The first assay available was CA15.3.
CA 15.3 is not specific for breast cancer because levels are also increased in patients with gastric, colorectal, lung, pancreas, ovarian, uterine, and cervical cancers. Levels are also elevated in some healthy women; 10% of patients with benign breast diseases, and 40% of patients with inflammatory liver diseases. CA 15.3 levels are not elevated during pregnancy or lactation.
CA 15.3 is not very sensitive in detecting early breast cancer; only 5 to 30% of patients with stage I and II cancer have elevated levels. CA 15.3 is not very useful in the differential diagnosis of breast masses, since it is elevated in some benign breast diseases and often not elevated in early breast cancer. CA 15.3 levels do not correlate with known prognostic factors, such as histologic grade, receptor status, or age. It does not have prognostic value for predicting which patients with metastatic disease will respond to therapy.
CA 15.3 is not sensitive enough to accurately monitor the disease course in patients with no evidence of disease after their primary therapy. CA 15.3's positive predictive value for relapse was only 41% for the first antigen elevation and 58% for two consecutive antigen elevations.
The American Society of Clinical Oncology published a practice guideline on the use of tumor markers in 1996. The expert panel concluded that CA15.3 is of limited value for detecting disease recurrence in postoperative patients because it is not a sensitive indicator of micro-metastases and the test generates false positive and false negative results.
A more promising application for CA 15.3 is monitoring the response to metastatic cancer therapy. In metastatic breast cancer, 70 to 90% of patients have elevated levels of mucin antigens. When mucin antigens are elevated, there is better correlation between mucin antigen serial levels and disease activity. Antigen levels must change at least 25% above the pre-change value before they are considered clinically significant.
For sensitivity, the correlation of changes in antigen levels with clinical course is defined as an increase of 25% or more in patients with progressive disease, a decrease of 25% or more in patients with regressive disease, and as a variation of less than 25% in patients with stable disease. Care must be taken not to over interpret rising antigen levels, since transient spikes lasting 30 to 100 days may occur shortly after therapy, due to tumor cell lysis. Monitoring the disease course of patients with metastatic disease is the most successful application of breast cancer mucin assays to date.
Reference range is 0-29 U/mL.
Specimen requirement is one SST tube of blood.
References
Geraghty JG, et al. CA 15-3 in patients with locoregional and metastatic breast carcinoma. Cancer. 1992;70(12):2831-2834
Kallioniemi OP, et al. Serum CA 15-3 assay in the diagnosis and follow-up of breast cancer. Br J Cancer. 1988;58(2):213-215
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