Female breast cancer has now surpassed lung cancer as the leading cause of global cancer incidence in 2020. The elevated incidence rates in higher HDI countries reflect a longstanding higher prevalence of reproductive and hormonal risk factors (early age at menarche, later age at menopause, advanced age at first birth, fewer number of children, less breastfeeding, menopausal hormone therapy, oral contraceptives) and lifestyle risk factors (alcohol intake, excess body weight, physical inactivity), as well as increased detection through organized or opportunistic mammographic screening.
Some serum tumor markers including HER/neu, CA15-3 and CEA have been reported to be elevated in some patients with breast cancer.
CA15-3 is recommended to be used in postoperative surveillance in patients with no evidence of disease, monitoring therapy in advanced disease, assessing prognosis. High preoperative levels (e.g. >30 U/L) always predict adverse outcome[2].
CEA can be used in post-operative surveillance in patients with no evidence of disease, monitoring therapy in advanced disease, especially if CA 15-3/BR 27.29 is not elevated. And it can also be used in assessing prognosis that high preoperative levels predict adverse outcome[2].
HER-2/neu proteins are transmembrane glycoproteins with tyrosine protein kinase activity and are members of the epidermal growth factor receptor protein (EGFR) family. The extracellularstructural domain (ECD) of HER-2/neu can be cleaved by metalloproteinases and released from the cell surface into the humoral circulation [3]. . Overexpression of HER-2/neu can potentially activate the EGFR signalling pathway, which can also promote EGFR-mediated transformation and tumourigenesis [4,5] . Abnormal serum HER-2/neu protein has been reported in 33% of breast cancer, 23% of locally recurrent breast cancer and 44% of metastatic breast cancer patients [6] . In addition, HER-2/neu protein has been reported to be overexpressed in many other types of tumours of epithelial origin, such as gastric, lung, and liver cancers .[7,8].
[1] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID: 33538338.
[2] Sturgeon CM, Duffy MJ, Stenman UH, Lilja H, Brünner N, Chan DW, Babaian R, Bast RC Jr, Dowell B, Esteva FJ, Haglund C, Harbeck N, Hayes DF, Holten-Andersen M, Klee GG, Lamerz R, Looijenga LH, Molina R, Nielsen HJ, Rittenhouse H, Semjonow A, Shih IeM, Sibley P, Sölétormos G, Stephan C, Sokoll L, Hoffman BR, Diamandis EP; National Academy of Clinical Biochemistry. National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem. 2008 Dec;54(12):e11-79. doi: 10.1373/clinchem.2008.105601. PMID: 19042984.
[3] Codony-Servat J, Albanell J, Lopez-Talavera JC, et al. Cleavage of the HER2 ectodomain is a pervanadate-activable process that is inhibited by the tissue inhibitor of metalloproteases-1 in breast cancer cells. Cancer Res. 1999 Mar 15;59(6):1196-1201.
[4] Ross JS, Fletcher JA. The HER-2/neu Oncogene in Breast Cancer: Prognostic Factor, Predictive Factor, and Target for Therapy. Oncologist. 1998;3(4):237-252.
[5]Meden H, Kuhn W. Overexpression of the oncogene c-erbB-2 (HER2/neu) in ovarian cancer: a new prognostic factor. Eur J Obstet Gynecol Reprod Biol. 1997 Feb;71(2): 173-179.
[6]Lam L, McAndrew N, Yee M, et al. Challenges in the clinical utility of the serum test for HER2 ECD. Biochim Biophys Acta. 2012 Aug;1826(1):199-208.
[7] Wu JT, Astill ME, Zhang P. Detection of the extracellular domain of c-erbB-2 oncoprotein in sera from patients with various carcinomas: correlation with tumor markers. J Clin Lab Anal. 1993;7(1):31-40.
[8]Myers RB, Brown D, Oelschlager DK, et al. Elevated serum levels of p105(erbB-2) in patients with advanced-stage
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