Breast Cancer Biomarkers

Candidate breast cancer biomarker
Protein Names Clinical Markers Human Swiss Prot # Comments Quality Products (Protein, antibody, ELISA kit & cDNA clone)
Angiopoietin 1   Q15389 Involved in vasculature modeling, it is increased in breast cancer (Caine et al. 2003). Angiopoietin 1 / ANG1 / ANGPT1
Angiopoietin 2   O15123 It is involved in vasculature modeling in that it is an antagonist of angiopoietin 2. It is increased in breast cancer (Caine et al. 2003). Angiopoietin-2 / ANG2
Breast cancer 2 early onset   P51587 BRCA2 is a breast cancer susceptibility gene. Five percent of early onset breast cancer cases express mutations in Brca 1 or 2 (Lalloo and Evans 1999). BRCA2
Small inducible cytokine A2(CCL2)   P13500 CCL2 is a monocyte, chemotactic and activating factor increased in some breast cancer (Lebrecht et al. 2004). CCL2/MCP-1
Coagulation factor XIII B chain   P05160 The protein carrier subunit of factor XIII, it crosslinks fibrin. It is decreased in breast cancer tissues (Jiang et al. 2003). Coagulation Factor XIII B chain
Endoglin   P17813 An angiogenesis factor increased in breast cancer (Li et al. 2000). Endoglin/CD105
Erythropoietin   P01588 A stimulator of erythropoiesis associated with malignant cells and tumor vasculature in breast cancer (Acs et al. 2001). Erythropoietin / EPO
E-selectin   P16581 An adhesion molecule, sE-selectins increased in metastatic breast cancer especially in patients with liver metastases (Hebbar and Peyrat 2000). E-Selectin/CD62e/SELE
Interleukin 6 signal transducer   P40189 A signal transducer molecule, increased in breast cancer (Karczewska et al. 2000). gp130/CD130
Hepatocyte growth factor yes P14210 A growth factor for a broad spectrum of tissues and cell types. Hepatocyte growth factor has no detectable protease activity. It is increased in breast cancer tissues (Parr et al. 2004). HGF / Hepatocyte Growth Factor
Intercellular Adhesion Molecule 1   P05362 A lymphocyte adhesion molecule elevated in melanoma (Boyano et al. 2000), hepatocellular cancer (Tsujisaki et al. 1991), breast cancer (Altomonte et al. 1999), and extranodal lymphomas (Lei and Johnson 2000). ICAM-1/CD54
Insulin yes P01308 Serum insulin levels were clearly higher in patients with breast cancer than in patients with benign breast disease and healthy controls (Han et al. 2005). Insulin Receptor
Lactotransferrin   P02788 An iron-binding protein that modulates iron metabolism, hematopoiesis, and immunologic reactions. It is increased in gastrointestinal, lung and breast cancer patients (Vasil'ev and Avdeev 1985). Lactotransferrin/LTF
Midkine   P21741 Midkine has heparin binding activity, and growth promoting activity, it is increased in breast cancer patients (Ikematsu et al. 2000). Midkine
Proliferating cell nuclear antigen   P12004 A DNA repair protein. Increased levels in breast cancer (Kushlinskii et al. 2004). PCNA
Urokinase plasminogen activator surface receptor, U-PAR   Q03405 The urokinase-type plasminogen activator receptor is a key molecule in the regulation of cell-surface plasminogen activation. It is increased in colorectal cancer and associated with poor prognosis in patients with metatatic breast cancer (Begum et al. 2004). PLAUR/CD87
Vascular cell adhesion molecule 1   P19320 VCAM-1 mediates the adhesion of monocytes and lymphocytes to cytokine-activated endothelium. It is correlated with microvessel density in early breast cancer tumors and increased in women with lymph node-positive and high-grade breast tumors (Byrne and Bundred 2000). VCAM-1/CD106
Fms-related tyrosine kinase 1, VEGFR1   P17948 An oncogene that is important for the control of cell proliferation and differentiation, it is reduced in breast cancer (Caine et al. 2003). VEGFR1/FLT-1
X box binding protein-1   P17861 A transcription factor essential for hepatocyte growth, the differentiation of plasma cells, immunoglobulin secretion, and the unfolded protein response. It is increased in identical twins with multiple myeloma(Munshi et al. 2004) hXBP-1 mRNA expression was increased in primary breast cancers but hardly detectable in non-cancerous breast tissue (Fujimoto et al. 2003). XBP1
17beta- Hydroxysteroid dehydrogenase type 1 (17HSD1)   x 17HSD1 converts estrone to estradiol in the ovary, placenta and the breast. Signals for 17HSD1 mRNA were detected in 16% of breast cancer specimens (Oduwole et al. 2004).  
Alpha-1-acid glycoprotein 1, orosomucoid   P02763 An acute phase protein showing a 3–4 fold increase during inflammation or tissue damage, levels peak 3–5 days after the initiating event. It is increased in breast cancer (Tesarova et al. 2003).  
Alpha-lactalbumin   P00709 The principle milk protein that functions in the synthesis of lactose, it is increased in some breast cancer patients (Vasil'ev and Avdeev 1985).  
Bone sialoprotein II   P21815 A noncollagenous bone protein increased in prostate, colon, and breast cancer (Fedarko et al. 2001).  
Breast cancer 1 early onset   P38398 The BRCA1 protein is a tumor suppressor that mediates DNA damage and repair, transcriptional activity and chromosomal stability. However, while inherited mutations of BRCA1 are responsible for about 40–45% of hereditary breast cancers, these mutations account for only 2–3% of all breast cancers (Rosen et al. 2003).  
CA 15.3 yes x A monoclonal antibody identified cancer antigen increased in patients with metastatic breast cancer (Lockhart et al. 1999).  
CA 27.29 yes x A monoclonal antibody identified cancer antigen most frequently used to follow response to therapy in patients with metastatic breast cancer (Perkins et al. 2003).  
Coagulation factor XIII A chain   P00488 The catalytic unit of factor XIII which crosslinks fibrin, is decreased in breast cancer tissues (Jiang et al. 2003).  
Estrogen receptor 1 yes P03372 The estrogen receptor is a steroid receptor which stimulates hormone-specific transcription of specific genes. Most breast cancers express estrogen and progesterone receptor (ERalpha and PR) (Clarke et al. 2005).  
Geminin   O75496 Geminin is a potent inhibitor of origin assembly and re-replication in multicellular eukaryotes and is a negative regulator of DNA replication during the cell cycle. Geminin expression is increased in 56% and of colon cancers, 58% of rectal cancers, and 60% of human primary breast cancers (Montanari et al. 2005).  
Keratin, type I cytoskeletal 19, cytokeratin 19   P08727 A cytoskeleton protein increased in bladder (Morita et al. 1997) and breast cancer (Grunewald et al. 2000).  
Lutropin beta chain, Luteinizing hormone   P01229 A gonadotropic hormone decreased in breast cancer (Micheli et al. 2004).  
Mammary Serum Antigen   x A serum glycoprotein on breast cancer cells detectable in serum. It may be an early prognostic marker in breast cancer (Smart et al. 1990).  
p65 oncofetal protein   x A novel member of the superfamily of genes that encode nuclear receptors for various hydro-phobic ligands such as steroids, vitamin D, retinoic acid, and thyroid hormones, it is increased in 90% of breast cancer patients (Mirowski et al. 1994).  
Pregnancy- associated plasma protein-A   Q13219 PAPP-A can bind a variety of cytokines and specifically cleave a binding protein for insulin-like growth factors, thereby serving as a modulator of cytokine activity. It is increased in breast cancer (Kuhajda and Eggleston 1985).  
Riboflavin carrier protein   x Riboflavin carrier proteins transports vitamin B2 across placental membranes, a process critical for maintenance of pregnancy. It is 3 to 4-fold higher in breast cancer patients. In addition, there seems to be a good correlation between rising RCP levels and disease progression (Karande et al. 2001).  
Breast cancer biomarker background

Breast cancer is still one of the leading causes of cancer death in women, but there has been a sustained decline in mortality rates over the last decades. Breast cancer treatment has experienced several changes in the past decades due to the discovery of specific prognostic and predictive breast cancer biomarkers that enable the application of more individualized therapies to different molecular subgroups.

In addition to the classical clinical prognostic factors of breast cancer, established molecular breast cancer biomarkers such as estrogen receptor and progesterone receptor have played a significant role in the selection of patients benefiting from endocrine therapy for many years. The shift toward an earlier diagnosis of breast cancer due to improved imaging methods and screening programs highlights the need for new factors and combinations of breast cancer biomarkers to quantify the residual risk of patients and to indicate the potential value of additional treatment strategies. The breast cancer biomarker of proliferation Ki67 has recently emerged as an important marker due to several applications in neoadjuvant therapy in addition to its moderate prognostic value. With the introduction of high-throughput technologies, numerous multigene signatures have been identified that aim to outperform traditional markers: current prospective clinical trials are seeking evidence for their definitive role in breast cancer. There exist many more factors and approaches that have the potential to become relevant in the near future including the detection of single disseminating and circulating tumor cells in blood and bone marrow as well as of circulating cell-free DNA and microRNA. Careful randomized prospective testing and comparison with existing established factors will be required to select those emerging breast cancer biomarkers that offer substantial cost-effective benefit and thereby justify their routine use for breast cancer therapy decision-making.

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