Serum Markers For Breast Cancer Research Articles

Serum Ca 15-3: A Useful Tumor Marker in the Prognostication of Locally Advanced Breast Cancer

Locally advanced breast cancer (LABC) continues to be a common presentation of breast cancer worldwide. Various serum markers have been studied to know the behaviour, metastasis and prognosis of breast cancer without going through any invasive procedure. CA 15-3 measures the protein product of the MUC 1 gene and is the most commonly used serum marker in breast cancer. The main use of serum CA 15-3 is monitoring therapy response and elevated levels are associated with metastatic disease and in non-metastatic patients, it is associated with poor prognosis. The aim of the study was to know the role of serum CA 15-3 level in diagnosis, prognosis and therapy response in patients with locally advanced breast cancer and to assess its relationship with other variables like tumor size, microscopic grade, nodal burden and Ki-67 antigen expression. Serum CA 15-3 levels significantly decreased after neo-adjuvant chemotherapy and mastectomy and it remained elevated in patients with suspected or hidden metastasis. Serum CA 15-3 levels exhibited positive statistically significant correlation with tumor size. DOI: 10.21276/AWCH.1782

Thymosin beta 10 is a key regulator of tumorigenesis and metastasis and a novel serum marker in breast cancer

BackgroundThymosin beta 10 (TMSB10) has been demonstrated to be involved in the malignant process of many cancers. The purpose of this study was to determine the biological roles and clinical significance of TMSB10 in breast cancer and to identify whether TMSB10 might be used as a serum marker for the diagnosis of breast cancer.MethodsTMSB10 expression was evaluated by immunohistochemical analysis (IHC) of 253 breast tumors and ELISA of serum from 80 patients with breast cancer. Statistical analysis was performed to explore the correlation between TMSB10 expression and clinicopathological features in breast cancer. Univariate and multivariate Cox regression analysis were performed to examine the association between TMSB10 expression and overall survival and metastatic status. In vitro and in vivo assays were performed to assess the biological roles of TMSB10 in breast cancer. Western blotting and luciferase assays were examined to identify the underlying pathway involved in the tumor-promoting role of TMSB10.ResultsWe found TMSB10 was upregulated in breast cancer cells and tissues. Univariate and multivariate analysis demonstrated that high TMSB10 expression significantly correlated with clinicopathological features, poor prognosis and distant metastases in patients with breast cancer. Overexpression of TMSB10 promotes, while silencing of TMSB10 inhibits, proliferation, invasion and migration of breast cancer cells in vitro and in vivo. Our results further reveal that TMSB10 promotes the proliferation, invasion and migration of breast cancer cells via AKT/FOXO signaling, which is antagonized by the AKT kinase inhibitor perifosine. Importantly, the expression of TMSB10 is significantly elevated in the serum of patients with breast cancer and is positively associated with clinical stages of breast cancer.ConclusionTMSB10 may hold promise as a minimally invasive serum cancer biomarker for the diagnosis of breast cancer and a potential therapeutic target which will facilitate the development of a novel therapeutic strategy against breast cancer.

Evaluation of human secretoglobins and MIC-1 as serum diagnostic biomarkers for breast cancer.

Abstract Abstract #2005 Using microarray and quantitative RT-PCR analysis, we found mRNA corresponding to several members of the human secretoglobin family and MIC-1 to be highly expressed in various cancer tissues, as compared to the corresponding normal tissues. Our target ECM2, known in the literature as Lipophilin B (LipB), was found to be upregulated in endometrial, uterine, breast and prostate cancer tissues. Our target ECM3, also known as Mammaglobin B (MamB) or Lipophilin C, was found to be upregulated in endometrial and uterine cancer tissues. DD-X065, also known in the literature as macrophage inhibitory cytokine-1 (MIC-1), a member of the transforming growth factor-beta (TGF-b) family, was found to be upregulated in breast, colon, lung, ovarian, and prostate cancer tissues.
 There is considerable evidence suggesting that members of the secretoglobin family exist predominantly as heterodimers and higher order complexes. Mammaglobin A (MamA) protein has been found to be present in breast tissue in a complex with LipB protein. We generated a series of mouse monoclonal antibodies directed against different complexes composed of members of the family, including MamA, LipB, and MamB. Employing these specific antibodies, we have developed sensitive immunoassays to measure serum levels of several of the complexes.
 In the current study, we evaluated serum from breast cancer patients for levels of two secretoglobin family complexes: MamA/LipB and MamB/LipB, as well as for MIC-1, utilizing our previously established ELISA assay2.
 The study comprised serum samples from 150 normal healthy individuals and 250 breast cancer patients. The sensitivity and specificity of the assays for detection of breast cancer were quantified by receiver operating characteristic (ROC) analysis. Compared to normal healthy individuals, the median serum concentrations of MamA/LipB was increased by approximately 2.8 fold in breast cancer, irrespective of stage. ROC analysis of breast cancer patients versus normal healthy individuals resulted in an AUC of 0.67 in all stages. For MamB/LipB, the median serum concentration in cancer serum was increased over normals by approximately 1.8 fold and the corresponding AUC was 0.62. The median serum concentration for MIC-1 in cancer serum was increased over normals by approximately 1.1 fold and the corresponding AUC was 0.61. The sensitivity of the MIC-1 assay was greater than that of any of the secretoglobin family complex assays at 90%, 95% and 98%.
 Our study suggests that MIC-1 and members of the secretoglobin family may be promising serum markers for breast cancer. Their utility may be improved when used in combination with other novel diagnostic biomarkers. Further studies are underway to validate the clinical potential of this family of markers.
 2Bistrup, A, et al., (2007) Proceedings of 98th AACR Annual Meeting, Los Angeles, CA. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2005.

Elevated levels of thymidine kinase 1 peptide in serum from patients with breast cancer

Objectives. Thymidine kinase (TK) has an important role in DNA synthesis and is thus related to cell proliferation and turn-over. Traditionally, TK has been measured by enzymatic activity or radioimmunoassays. These assays are difficult to adapt to random access instruments. The aim of this study was to evaluate a new immunological sandwich assay for detection of TK peptides in serum from breast cancer patients.Material and methods. Serum samples were collected from patients with breast cancer and stored frozen at −70°C. The samples were collected after surgery, after metastatic tumor recurrence and after chemotherapy due to tumour recurrence. Patients’ serum samples were analysed by the TK enzyme-linked immunosorbent assay (ELISA).Results. In receiver operating characteristics (ROC) analyses of TK1 for diagnosis of breast cancer, the area under the curve (AUC) collected four weeks after surgery was 0.56 (95% CI 0.47–0.65), for samples collected postsurgically after tumour recurrence 0.73 (95% CI 0.65–0.80), and after chemotherapy 0.64 (95% CI 0.56–0.72).Conclusions. This study indicates that the tumour proliferation marker TK has a potential as a serum marker in breast cancer. Further studies are warranted to verify this observation.

Mammaglobin A: A Promising Marker for Breast Cancer

Most tumor markers in routine clinical practice lack organ specificity (1). For example, CA 15-3, BR 27.29, and carcinoembryonic antigen, which are widely used serum markers for breast cancer, can be increased in patients with most types of adenocarcinoma, especially if distant metastases are present [for a review, see Ref. (2)]. Using a modified differential display technique, Watson and Fleming (3)(4) identified a novel gene that appeared to be expressed only in breast tissue. This gene, which was designated mammaglobin ( MG ), was found to encode a 93-amino acid protein with a predicted molecular mass of 10.5 kDa (4). MG mRNA expression was reported to be increased at least 10-fold relative to nonmalignant breast tissue in 8 of 35 (23%) breast carcinomas (4), and MG protein was detected by immunohistochemistry in 81 of 100 breast cancers (5). MG was detected by quantitative reverse transcription-PCR in 31 of 42 (74%) primary breast cancers (6) and was either undetectable or present at low concentrations in small numbers of nonbreast tissues (4)(5)(6). In 1998, Becker et al. (7) identified a new gene with marked sequence identities to MG . This new gene was named mammaglobin B ( MGB ) (7), and the original MG was redesignated mammaglobin A ( MGA ). Both MGA and MGB and several related genes [e.g., Clara cell 10-kDa protein, lipophilin A, and lipophilin B ( LPB )] are localized in a dense cluster on chromosome 11q12.2 …

Evaluation of chromogranin A expression in serum and tissues of breast cancer patients.

Human chromogranin A (CgA) is a member of the granin family and is widely distributed in large dense core granules of endocrine and neuroendocrine cells. A variety of non-neuroendocrine carcinomas arising in various tissues show patterns of neuroendocrine differentiation. Expression of CgA has been documented in epithelial cells of normal mammary gland as well as in breast cancers, and elevation of serum CgA has been detected in patients with breast cancer. Our study was undertaken to evaluate the relationship between serum CgA levels and neuroendocrine features in breast cancer. In addition, we evaluated the expression of serum CgA in patients affected by breast cancer compared to controls and the relationship between serum CgA and tumor histology, extent of disease, lymph node status, tumor stage and serum CA 15.3 levels. We enrolled 266 patients with infiltrating ductal or lobular breast carcinoma and a group of 100 age-matched healthy women serving as controls. Serum CgA and CA 15.3 were assayed by specific immunoradiometric methods. The overall sensitivity of CgA and CA 15.3 was 0.06 and 0.34, respectively (chi2 19.1, p<0.0005). No relationship was found between serum levels of CgA and tumor histology, extent of disease, lymph node status or tumor stage while serum levels of CA 15.3 were strongly correlated with all these variables but tumor histology. No relationship was found between serum levels of CgA and CA 15.3. Immunostaining against CgA, CgB, NSE and synaptophysin was performed on primary tumor tissue of 14 serum CgA-positive and 24 serum CgA-negative patients and was negative in all cases. We also evaluated eight cases of pathologically-proven neuroendocrine breast cancer: only four and two of these showed positive CgA immunostaining and increased serum CgA concentration, respectively. In conclusion, serum CgA assay offers no additional information regarding the presence, the extent and the histology of breast cancer compared to the CA 15.3 assay. Moreover, serum CgA was not an accurate marker to identify or exclude the rare neuroendocrine differentiation of breast cancer. We therefore conclude that CgA is not useful as a serum marker in breast cancer.

CA 15-3: a prognostic marker in breast cancer.

CA 15-3 (also known as MUC1) is the most widely used serum marker in breast cancer. MUC1 is a large transmembrane glycoprotein which is frequently overexpressed and aberrantly glycosylated in cancer. Physiologically, MUC1 appears to play a role in cell adhesion and the high levels present in cancer may be causally involved in metastasis. At present the main uses of CA 15-3 are in preclinically detecting recurrent breast cancer and monitoring the treatment of patients with advanced breast cancer. In a prospective study of 368 patients we show that patients with high preoperative levels of CA 15-3 (>30.4 U/mL) had a worse outcome than patients with low levels of the marker. In multivariate analysis CA 15-3 as a prognostic marker was independent of both tumor size and nodal status. Furthermore, in multivariate analysis the prognostic impact of CA 15-3 was stronger than that of tumor size and at least as strong as nodal status. CA 15-3 may thus be the first independent prognostic serum marker in breast cancer.

Serum Markers for Breast Cancer

A considerable number of tumour markers and other laboratory tests are used for follow up and evaluation of breast cancer patients. No marker presently available is sensitive enough for early diagnosis and screening, but markers can be used to evaluate response to therapy and for early detection of a relapse. Of the markers presently available, CA 15-3 and CEA are mostly used. CA 15-3 appears to be somewhat more sensitive than CEA. When a cut-off level giving 97.5% specificity is used, the sensitivity of these assays is only about 5-25% in local disease and 50-70% in advanced disease. The combined use of these markers increase the sensitivity by 5-10%. The CA 15-3 assay measures a family of molecules called breast mucins, and several newer assays including MCA, MSA, CA 549, CA M26, CA M29 and BCM appear to measure members of the same family. The results obtained by these assays and with CA 15-3 correlate fairly well. So far none of the new assays has proven superior to CA 15-3. Of patients with advanced cancer, 20-30% are negative for the above mentioned markers. For these patients it may be worthwhile to try other markers not related with the above mentioned.

Serum Markers for Breast Cancer

Serum Markers for Breast Cancer