Serological Tumor Markers such as CA15-3 and CEA in Breast Cancer

By Priyanka Varma

BURLINGAME, Calif.

Sept. 27st, 2022

There are several serological tumor markers described in the literature for breast cancer, like Cancer Antigen 15-3 (CA15-3), BR 27.29, Carcinoembryonic Antigen (CEA), Tissue Polypeptide Antigen, tissue polypeptide specific antigen; out of these, the more frequently assessed ones are CA15-3 and CEA [Table 1]. However, owing to lack of sensitivity and specificity, none of the above markers can be utilized for early detection of breast cancer [1].

CA15-3 is a protein/tumor marker produced by Breast Cancer cells, typically found in metastasized breast cancer versus early stages of the disease, detected by a blood test. However, it is not specific to cancerous cells as non-cancerous conditions like endometriosis, pelvic inflammatory disease, liver disease also show an increase in the level of CA15-3 albeit not as high as with cancer [2]. CA15-3 assay measures polymorphic epithelial mucin(PEM), also known as episalin, a product of the MUC1 gene. PEM is shed form epithelial cells not only in breast, but also in lung, colon, pancreas, and ovary. MUC1 gene gets 10-fold upregulated in breast cancer as compared to healthy cells with decreased glycosylation and development of monoclonal antibodies owing to incomplete exposure of the core polypeptide backbone [3].CA15-3 is used as a prognostic marker and for monitoring treatment in patients with advanced breast cancer. A higher pre-operative concentration of bothCA15-3 (25-40 Kilo Units/ L) and CEA denote poor prognostic outcome. CA15-3concentrations gradually increase with advancing stage of breast cancer, ranging from 10% (Stage I) to 75% (stage IV) [1].

CEA is another tumor marker used for breast cancer and showed significantly higher levels in breast cancer patients versus healthy women(p<0.0001) in a study conducted on 47 breast cancer patients. This study also showed that metastatic breast cancer had higher level of this tumor marker as compared to localized disease. However, CEA is also not specific to breast cancer as its levels were also elevated in other cancers versus healthy women(p<0.001). CEA is also seen in bladder, lung, ovarian, thyroid cancers besides breast cancer [4, 5].  

In a study conducted on breast cancer patients, it was observed that significantly more women with metastatic breast cancer had increasedCA15-3 versus CEA levels (p<0.001) [6]. The American Society for Clinical Oncology clinical guidelines confirm the role of CA15-3 and CEA for monitoring response to treatment of metastatic breast cancer, with a treatment failure indicated by a rise of 20%-30% marker level in the absence of measurable disease [3].

Even though some studies depicted an early treatment based on increasing tumor marker concentration had improved prognosis, it was not recommended for asymptomatic patients to start new therapy based on tumor marker level [1].  

Bibliography:

1.    Michael J Duffy, Serum Tumor Markers in Breast Cancer: Are They of Clinical Value?, Clinical Chemistry, Volume52, Issue 3, 1 March 2006, Pages 345–351, https://doi.org/10.1373/clinchem.2005.059832

2.    Cancer antigen 15-3 (CA15-3) test | Canadian Cancer Society

3.    Lori J. Sokoll, Daniel W. Chan, Chapter 44 -Tumor markers, Editor(s): William Clarke, Mark A. Marzinke, Contemporary Practice in Clinical Chemistry (Fourth Edition) Academic Press, 2020,Pages 779-793,ISBN9780128154991,https://doi.org/10.1016/B978-0-12-815499-1.00044-2.(https://www.sciencedirect.com/science/article/pii/B9780128154991000442)

4.    Mujagić Z, Mujagic H, Prnjavorac B. The relationship between circulating carcinoembryonic antigen (CEA) levels and parameters of primary tumor and metastases in breast cancer patients. Med Arh.2004;58(1):23-6. PMID: 15017899.

5.    CEA Test (Carcinoembryonic Antigen): What It Is & Results (clevelandclinic.org)

6.    Comparison of circulating CA15-3 and carcinoembryonic antigen levels in patients with breast cancer. D F Hayes, V R Zurawski Jr, and D W Kufe; Journal of Clinical Oncology 1986 4:10, 1542-1550

7.    The CA 15-3 test and breast cancer: What it is and results (medicalnewstoday.com)

8.    Normal CA 27-29(Carbohydrate Antigen) in a blood test (mrlabtest.com)

9.    Tissue Polypeptide Antigen - an overview | ScienceDirect Topics

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