CA 15-3

Other names: Cancer Antigen 15-3, Cancer Antigen (CA) 15-3, CA 153

check icon Optimal Result: 0 - 31 U/mL.

Cancer antigen 15-3 (CA 15-3) is a tumor marker used to monitor the response to breast cancer treatment and detect disease recurrence. The reference range of serum CA 15-3 is typically less than 30 U/mL, but the upper limit varies based on the specific laboratory and test kit used. It's important to note that results obtained from different assay kits, methods, or laboratories should not be used interchangeably.

CA 15-3 levels are commonly employed to monitor metastatic breast cancer during active therapy. However, these levels must be used in conjunction with the patient's history, physical examination, and diagnostic imaging. A decrease in marker levels during treatment may indicate a positive response to therapy, while stable or increasing levels despite adequate treatment may suggest treatment failure or disease recurrence.

Additionally, CA 15-3 measurement can be used to survey disease recurrence after treatment of metastatic breast cancer. In cases without measurable disease, an increase in CA 15-3 levels could indicate treatment failure. However, it's worth noting that CA 15-3 levels can temporarily rise during the first 4-6 weeks of starting therapy, and this transient rise usually does not correlate with disease progression.

Higher CA 15-3 levels have been associated with more advanced stages of breast cancer or larger tumor burden. When the tumor produces CA 15-3, marker levels will increase as the tumor grows. The highest levels of CA 15-3 are often observed in metastatic breast cancer, especially when metastases are present in the liver or bones. However, CA 15-3 can be low or absent in some cases since not all breast cancers produce this marker, and early-stage breast cancers may not have detectable CA 15-3 levels. As a result, normal CA 15-3 levels do not guarantee the absence of localized or metastatic breast cancer.

Studies have shown that in 62% of patients treated for early breast cancer in whom metastases were found, CA 15-3 levels were above 30 U/mL at the time of metastases discovery. In 37% of patients, the higher CA 15-3 level was the first sign leading to the diagnosis of metastases, with liver and bone metastases being the most common.

It's essential to consider that elevated CA 15-3 levels can also be seen in healthy individuals, as well as in benign and other malignant conditions. Consequently, elevated levels need to be interpreted within the context of the patient's medical history, physical examination, diagnostic imaging, and laboratory workup.

While CA 15-3 testing can provide valuable information in monitoring response to treatment and detecting disease recurrence, it has limitations. The sensitivity of CA 15-3 is low in early-stage breast cancer, and it may not be detected in all breast cancers. Moreover, its overall specificity is limited, making it challenging to reliably screen, diagnose, or stage breast cancer based solely on CA 15-3 levels.

In conclusion, CA 15-3 is a useful marker for monitoring breast cancer treatment response and detecting disease recurrence, particularly in cases of metastatic breast cancer. However, it should be used in combination with other clinical and imaging assessments for a comprehensive evaluation of the patient's condition. Furthermore, its limitations should be considered when interpreting the results, and more research is needed to explore its full clinical utility and impact on patient outcomes.

References:

De Cock L, Heylen J, Wildiers A, Punie K, Smeets A, Weltens C, Neven P, Billen J, Laenen A, Wildiers H. Detection of secondary metastatic breast cancer by measurement of plasma CA 15.3. ESMO Open. 2021 Aug;6(4):100203. doi: 10.1016/j.esmoop.2021.100203. Epub 2021 Jul 13. PMID: 34271308; PMCID: PMC8282974.

Bon GG et al. Clinical and technical evaluation of ACS™BR serum assay of MUC1 gene-derived glycoprotein in breast cancer, and comparison with CA 15-3 assays. Clinical Chemistry. 1997. 43(4):585-593.

Wu JT. Expression of monoclonal antibody-defined tumor markers in four carcinomas. Ann Clin Lab Sci. 1989 Jan-Feb;19(1):17-26. PMID: 2916833.

Duffy MJ, Shering S, Sherry F, McDermott E, O'Higgins N. CA 15-3: a prognostic marker in breast cancer. Int J Biol Markers. 2000 Oct-Dec;15(4):330-3. doi: 10.1177/172460080001500410. PMID: 11192829.

Klee GG, Schreiber WE. MUC1 gene-derived glycoprotein assays for monitoring breast cancer (CA 15-3, CA 27.29, BR): are they measuring the same antigen? Arch Pathol Lab Med. 2004 Oct;128(10):1131-5. doi: 10.5858/2004-128-1131-MGGAFM. PMID: 15387710.

Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, Somerfield MR, Hayes DF, Bast RC Jr; American Society of Clinical Oncology. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007 Nov 20;25(33):5287-312. doi: 10.1200/JCO.2007.14.2364. Epub 2007 Oct 22. PMID: 17954709.

Ebeling FG, Stieber P, Untch M, Nagel D, Konecny GE, Schmitt UM, Fateh-Moghadam A, Seidel D. Serum CEA and CA 15-3 as prognostic factors in primary breast cancer. Br J Cancer. 2002 Apr 22;86(8):1217-22. doi: 10.1038/sj.bjc.6600248. PMID: 11953875; PMCID: PMC2375330.

Wang G, Qin Y, Zhang J, Zhao J, Liang Y, Zhang Z, Qin M, Sun Y. Nipple discharge of CA15-3, CA125, CEA and TSGF as a new biomarker panel for breast cancer. Int J Mol Sci. 2014 May 28;15(6):9546-65. doi: 10.3390/ijms15069546. PMID: 24879526; PMCID: PMC4100109.

Kokko R, Holli K, Hakama M. Ca 15-3 in the follow-up of localised breast cancer: a prospective study. Eur J Cancer. 2002 Jun;38(9):1189-93. doi: 10.1016/s0959-8049(01)00429-4. PMID: 12044504.

Nicolini A, Tartarelli G, Carpi A, Metelli MR, Ferrari P, Anselmi L, Conte M, Berti P, Miccoli P. Intensive post-operative follow-up of breast cancer patients with tumour markers: CEA, TPA or CA15.3 vs MCA and MCA-CA15.3 vs CEA-TPA-CA15.3 panel in the early detection of distant metastases. BMC Cancer. 2006 Nov 20;6:269. doi: 10.1186/1471-2407-6-269. PMID: 17116247; PMCID: PMC1684262.

Kruse V, Van de Wiele C, Borms M, Maes A, Pottel H, Sathekge M, Cocquyt V. CA 15.3 measurements for separating FDG PET/CT positive from negative findings in breast carcinoma recurrence. Factors influencing the area under the ROC curve. Nuklearmedizin. 2014 Aug 6;53(4):131-8. doi: 10.3413/Nukmed-0634-13-12. PMID: 25100557.

Cervino AR, Saibene T, Michieletto S, Ghiotto C, Bozza F, Saladini G, Evangelista L. Correlation between cancer antigen 15.3 value and qualitative and semiquantitative parameters of positron emission tomography/computed tomography in breast cancer patients. Curr Radiopharm. 2014;7(1):20-8. doi: 10.2174/1874471007666140515111134. PMID: 24836946.

Nicolini A, Carpi A, Ferrari P, Morganti R, Mazzotti V, Barak V, Duffy MJ. An individual reference limit of the serum CEA-TPA-CA 15-3 tumor marker panel in the surveillance of asymptomatic women following surgery for primary breast cancer. Cancer Manag Res. 2018 Dec 13;10:6879-6886. doi: 10.2147/CMAR.S177522. PMID: 30588093; PMCID: PMC6300365.

Heylen J, Punie K, Smeets A, Neven P, Weltens C, Laenen A, Wildiers H. Elevated CA 15.3 in Newly Diagnosed Breast Cancer: A Retrospective Study. Clin Breast Cancer. 2022 Aug;22(6):579-587. doi: 10.1016/j.clbc.2022.04.007. Epub 2022 Apr 30. PMID: 35668001.

Sturgeon C. Practice guidelines for tumor marker use in the clinic. Clin Chem. 2002 Aug;48(8):1151-9. PMID: 12142367.

What does it mean if your CA 15-3 result is too high?

Elevation of CA 15-3 levels can be seen in healthy individuals, in benign conditions, and in other malignant conditions. However, CA 15-3 levels tend to remain relatively stable over time in benign conditions; thus, elevated levels need to be interpreted within the context of the patient’s history and physical examination, diagnostic imaging, and laboratory workup.

Benign causes of elevated CA 15-3 levels are as follows:

→ Chronic hepatitis

→ Liver cirrhosis

→ Tuberculosis

→ Sarcoidosis

→ Benign breast disease

→ Pelvic inflammatory disease

→ Endometriosis

→ Systemic lupus erythematosus

→ Lactation and pregnancy

Malignant causes of elevated CA 15-3 levels are as follows:

→ Small cell lung cancer

→ Non-small cell lung cancer

→ Liver cancer

→ Colon cancer

→ Ovarian cancer

→ Endometrial cancer

→ Pancreatic cancer

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