Tumor Markers In Breast Cancer Research Articles

Tumor marker usage and medical care costs among older early-stage breast cancer survivors.

Although American Society of Clinical Oncology guidelines discourage the use of tumor marker assessment for routine surveillance in nonmetastatic breast cancer, their use in practice is uncertain. Our objective was to determine use of tumor marker tests such as carcinoembryonic antigen and CA 15-3/CA 27.29 and associated Medicare costs in early-stage breast cancer survivors. By using Surveillance, Epidemiology, and End Results-Medicare records for patients diagnosed with early-stage breast cancer between 2001 and 2007, tumor marker usage within 2 years after diagnosis was identified by billing codes. Logistic regression models were used to identify clinical and demographic factors associated with use of tumor markers. To determine impact on costs of care, we used multivariable regression, controlling for other factors known to influence total medical costs. We identified 39,650 eligible patients. Of these, 16,653 (42%) received at least one tumor marker assessment, averaging 5.7 tests over 2 years, with rates of use per person increasing over time. Factors significantly associated with use included age at diagnosis, diagnosis year, stage at diagnosis, race/ethnicity, geographic region, and urban/rural status. Rates of advanced imaging, but not biopsies, were significantly higher in the assessment group. Medical costs for patients who received at least one test were approximately 29% greater than costs for those who did not, adjusting for other factors. Breast cancer tumor markers are frequently used among women with early-stage disease and are associated with an increase in both diagnostic procedures and total cost of care. A better understanding of factors driving the use of and the potential benefits and harms of surveillance-based tumor marker testing is needed.

Reconnoitring the status of prostate specific antigen and its role in women.

Prostate specific antigen is considered to be a tumour marker having maximum utility and specificity for prostate cancer since decades. After the discovery of methods to quantify different molecular fractions of prostate specific antigen (PSA), its usefulness in diagnosing early prostate cancer cases has increased tremendously. The "specificity" of PSA, is now challenged by many studies which proved that PSA, once believed to be secreted exclusively by prostatic epithelium, is also present in females. The exact biological role of extraprostatic PSA is still debatable though many theories substantiated by in vitro evidence has been put forward. With the advent of ultrasensitive analytical techniques, PSA is now quantifiable in female serum in its various molecular forms and this has led to many assumptions of it being useful as a marker in female breast cancers. In a similar scenario to prostate cancer, the ratio of free to total PSA is shown to be useful in detecting early breast cancer cases. It is also shown to be a good prognostic indicator and a predictor of response to therapy and recurrence. Apart from its role in breast cancer, it has been advocated to be a marker of hyper androgenic states in women like hirsutism and polycystic ovarian syndrome. Conflicting reports regarding the role of extra prostatic PSA is accumulating but it has been proven beyond doubt that PSA is no longer specific and confined to prostate gland. Various studies have registered that PSA is an ubiquitous molecule, secreted by hormone responsive organs and its synthesis is stimulated by androgens and progesterone but not oestrogens. In this article, a review of various literatures is done about the presence of extra prostatic PSA, its probable role in those sites as well as its utility as a tumour marker in breast cancer.

Clinical significance of circulating tumor cells (CTCs) with respect to optimal cut-off value and tumor markers in advanced/metastatic breast cancer.

Although carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) are useful tumor markers (TMs) in metastatic breast cancer (MBC), circulating tumor cells (CTCs) are also detected in patients with advanced or metastatic breast cancer. We analyzed CTCs in MBC patients in order to establish the optimal cut-off value, to evaluate the prognostic utility of CTC count, and to clarify whether CTC count could provide information in addition to CEA and CA15-3. We studied 98 MBC patients enrolled between June 2007 and March 2013. To quantify CTCs, 7.5 ml of blood was collected and CEA and CA15-3 were measured simultaneously. CTCs were counted using the CellSearch™ System. The CTC count was dichotomized as 0 (CTC-negative) or ≥1 (CTC-positive). The clinical significance of CTCs was evaluated in terms of its relationship with levels of CEA and CA15-3. Associations between qualitative variables were evaluated using the chi-square test. In order to evaluate the predictive value of CTCs for advanced or metastatic breast cancer, multivariate Cox proportional hazards modeling was used to calculate hazard ratios. With a CTC cut-off value of 1, there were 53 (54.1 %) CTC-negative patients and 45 (45.9 %) CTC-positive patients. Patients in the CTC-positive group had worse survival than those in the CTC-negative group (p < 0.0001). Seventy-one patients (72.4 %) had TM data at the time of CTC testing. To study the relationship between CTCs and TMs, we divided patients into normal TM and high TM groups. In the normal TM group, the CTC-negative patients had statistically significant survival than the CTC-positive patients (p = 0.005). The data suggested that CTC count could provide additional prognostic information beyond TMs for advanced/metastatic breast cancer. In multivariate analysis, the only significant predictor of overall survival was CTC ≥ 1 (hazard ratio, 3.026; 95 % confidence interval 1.350-6.784). We found that a CTC cut-off value of 1 is appropriate in patients with advanced/metastatic breast cancer. CTCs could yield additional information beyond CEA and CA15-3.

Ubiquitin-Conjugating Enzyme UBE2C Is Highly Expressed in Breast Microcalcification Lesions

Ubiquitin-conjugating enzyme 2C (UBE2C) contributes to ubiquitin-mediated proteasome degradation of cell cycle progression in breast cancer. Microcalcification (MC) is the most common mammographic feature of early breast cancer. In this study, we evaluated whether UBE2C could be a tumor marker of early breast cancer with MC found on screening mammography. UBE2C protein and mRNA expression were measured in breast core biopsy pairs of MC and adjacent non-MC breast tissue from each subject. Immunohistochemistry revealed UBE2C positivity in 69.4% of MC samples and 77.6% negativity in non-MC samples (p<0.0001). On RT-qPCR, 56.1% of malignant MC lesion samples showed high mRNA level of UBE2C and 80% of benign MC lesion samples showed a low level of UBE2C (p = 0.1766). We investigated the carcinogenic role of UBE2C in MCF-7 breast cancer cells with UBE2C knockdown; UBE2C knockdown downregulated cell proliferation and activated the cellular apoptosis pathway to inhibit cell colony formation. Furthermore, UBE2C expression was associated with that of carcinogenic genes human epidermal growth factor receptor type 2 (HER2), cellular c-Ki-ras2 proto-oncogene (KRAS), vascular endothelial growth factor (VEGF), CXC chemokine receptor 4 (CXCR4), C-C motif chemokine 5 (CCL5), neural precursor cell expressed, developmentally downregulated 9 (NEDD9) and Ras homolog family member C (RhoC). UBE2C may be a marker for diagnosis of nonpalpable breast lesions but not benign or malignant tumors in mammography core biopsies. Suppression of UBE2C may be a potential therapy target in breast cancer.

Role of serum carcinoembryonic antigen (CEA) as a tumor marker in breast cancer

Background: There is a need for biological prognostic indicators in breast cancer that would, alone or in combination with others, be sufficient to predict disease recurrence and, hence, be the basis for supplemental treatment after local therapy. Aims: To investigate the association between tumor marker serum carcinoembryonic antigen (CEA) and clinicopathological parameters in patients with breast cancer. Methods: A total of 134 patients with breast cancer treated in a single general surgery unit between January 2012 and November 2013 were included in the study, with age ranging between 28 and 73 years. Serum CEA values were compared before and after the treatment of breast cancer, between different histological types of breast cancer patients, between axillary lymphnode-positive and axillary lymphnode-negative patients, and between premenopausal and postmenopausal breast cancer patients. Data were analyzed using the statistical software SPSS version 19. Results: There was significant change in the values of serum CEA before (10.71 ± 2.79 ng/ml) and after the surgery for breast cancer (9.73 ± 3.00 ng/ml) (P < 0.006). There was further decline in the serum CEA level after a course of chemo-radiotherapy (7.30 ± 2.79 ng/ml) (P < 0.001). There was no significant difference between the different histological types of breast cancer (P value 0.55). The difference was significant in patients who were axillary lymphnode positive and negative (P < 0.001). There was no significant difference in premenopausal and postmenopausal breast cancer patients (P value 0.86). Conclusions: Serum CEA is a tumor marker of breast carcinoma. Its level decreased after treatment. This decrease is found more after chemo/radiotherapy following surgery. Serum CEA values are found to be elevated in patients with axillary lymphnode metastasis. There is no significant relation with the histologic type of breast cancer and menopausal status of the patient.

Clinical significance of serum miR-21 in breast cancer compared with CA153 and CEA.

MicroRNA-21 (miR-21) has been shown to be a key regulator of carcinogenesis. There were few reports about the comparison of serum miR-21 with conventional tumor markers. This study aimed to explore the diagnostic value of circulating miR-21 as a tumor marker in breast cancer (BC) and compare it with CA153 and carcinoembryonic antigen (CEA). Circulating miR-16 and miR-21 were amplified and quantitatively detected by real-time PCR in 89 BC patients and 55 healthy controls. The levels of CA153 and CEA were measured through electrochemiluminescence assays. Then the sensitivity in diagnosis of BC was compared among miR-21, CA153 and CEA. The level of serum miR-21 was significantly higher in BC patients than controls (P<0.001). The sensitivity and specificity of miR-21 were 87.6% and 87.3%, respectively, whereas the sensitivities of CEA and CA153 were only 22.47% and 15.73%. Compared with CEA and CA153, serum miR-21 has a higher sensitivity in diagnosis of BC. Although not correlated with the status of ER, PR and clinical stages, serum miR-21 may be a potential diagnostic indicator for BC, especially for the early stage.

Breast Cancer Risk Prediction with Heterogeneous Risk Profiles According to Breast Cancer Tumor Markers

Relationships between some risk factors and breast cancer incidence are known to vary by tumor subtype. However, breast tumors can be classified according to a number of markers, which may be correlated, making it difficult to identify heterogeneity of risk factors with specific tumor markers when using standard competing-risk survival analysis. In this paper, we propose a constrained competing-risk survival model that allows for assessment of heterogeneity of risk factor associations according to specific tumor markers while controlling for other markers. These methods are applied to Nurses' Health Study data from 1980-2006, during which 3,398 incident invasive breast cancers occurred over 1.4 million person-years of follow-up. Results suggested that when estrogen receptor (ER) and progesterone receptor (PR) status are mutually considered, some risk factors thought to be characteristic of "estrogen-positive tumors," such as high body mass index during postmenopause and increased height, are actually significantly associated with PR-positive tumors but not ER-positive tumors, while other risk factors thought to be characteristic of "estrogen-negative tumors," such as late age at first birth, are actually significantly associated with PR-negative rather than ER-negative breast cancer. This approach provides a strategy for evaluating heterogeneity of risk factor associations by tumor marker levels while controlling for additional tumor markers.

Toward a Science of Research Prioritization? The Use of Value of Information by Multidisciplinary Stakeholder Groups

In this issue of Medical Decision Making, Carlson and others describe the process of convening an external group of diverse stakeholders to identify 3 high-priority cancer genomics tests for further research and to rank these in order of priority for conducting further research. The external multidisciplinary stakeholder advisory group involved 13 members, including patient advocates, payers, test developers, a regulator, policy makers, and practicing oncologists. This group committed to meet over 2 years to help the South West Oncology Group (SWOG) leadership and investigators identify and prioritize future research areas and to help assess where scarce research funds would be best spent. The stakeholder group began by identifying 3 topics for research from a larger number of possible options in the area of cancer genomic tests. They were provided with a landscape review, and they developed priority-setting criteria in collaboration with the SWOG investigators to undertake this process. They identified 3 genomic tests for which further research would be useful: 1) ERCC1 expression testing for platinum-based adjuvant therapy in fully resected earlystage non–small cell lung cancer (NSCLC); 2) epidermal growth factor receptor (EGFR) mutation testing for erlotinib maintenance therapy after firstline chemotherapy in advanced NSCLC, and 3) breast cancer tumor markers (BC markers) for detection of recurrence after primary breast cancer therapy. The stakeholder group was subsequently provided with value of information (VOI) analyses to quantify the value of conducting further research on each of these genomic tests. More specifically, they were provided with expected value of perfect information (EVPI) analyses, which estimate the upper level dollar value of reducing the uncertainty about which strategy is the optimal intervention. Providing the stakeholder group with these analyses involved a number of complex steps: developing simulation models for each genomic test, calculating the EVPI, training the external group of stakeholders in understanding what these results mean and how to use them, and discussing the results and reranking their choices based on what they may have learned from the VOI analyses. Indeed, Carlson and colleagues describe how the stakeholder group ranking of the tests changed from 1) ERCC1, 2) EGFR, 3) BC markers to 1) ERCC1, 2) BC markers, 3) EGFR. The BC markers ranked higher relative to EGFR compared with the initial prioritization vote in part because the VOI analyses helped the stakeholders appreciate the benefits of studying a technology associated with high uncertainty. Of the stakeholders, 69% reported finding these analyses helpful and 53% reported that they changed their priority ranking because of the information provided by the VOI results. The science of research prioritization has made important advances over the past 20 years. Research prioritization has moved from an approach largely based on convening groups of experts for unstructured discussions to a scientific process that studies who and how to engage in priority-setting decisions and provides measurements of the value provided Received 11 March 2013 from Patient Centered Outcomes Research Institute (RLF); Department of Medicine, Department of Economics, and the Harris School of Public Policy Studies at the University of Chicago (DOM). Accepted for publication 20 March 2013.

Effects of Pomegranate Seed Oil and Tamoxifen on Mastectomy Breast Cancer Women

The present study was designed to study the effects of pomegranate and tamoxifen on breast cancer tumor marker (CA 15-3), aromatase enzyme, triglyceride (TG), cholesterol, and lactate dehydrogenase (LDH) in mastectomy women. The results indicates that tumor marker level was increased significantly in women without treatment while the tumor marker was significantly decreased in both pomegranate-tamoxifen combination and tamoxifen group, in addition, the level of aromatase and cholesterol was significantly decreased in pomegranate-tamoxifen combination group when compared with other two remaining groups. LDH level was significantly decreased in both tamoxifen and pomegranate-tamoxifen combination groups when compared with untreated group. However, the level of TG remains unchanged in all groups.

Differential Expression of Growth Factor Receptors and Membrane-Bound Tumor Markers for Imaging in Male and Female Breast Cancer

IntroductionMale breast cancer accounts for 0.5–1% of all breast cancers and is generally diagnosed at higher stage than female breast cancers and therefore might benefit from earlier detection and targeted therapy. Except for HER2 and EGFR, little is known about expression of growth factor receptors in male breast cancer. We therefore investigated expression profiles of growth factor receptors and membrane-bound tumor markers in male breast cancer and gynecomastia, in comparison with female breast cancer.MethodsTissue microarrays containing 133 male breast cancer and 32 gynecomastia cases were stained by immunohistochemistry for a panel of membrane-bound targets and compared with data on 266 female breast cancers.ResultsGrowth factor receptors were variably expressed in 4.5% (MET) up to 38.5% (IGF1-R) of male breast cancers. Compared to female breast cancer, IGF1-R and carbonic anhydrase 12 (CAXII) were more frequently and CD44v6, MET and FGFR2 less frequently expressed in male breast cancer. Expression of EGFR, HER2, CAIX, and GLUT1 was not significantly different between male and female breast cancer. Further, 48.1% of male breast cancers expressed at least one and 18.0% expressed multiple growth factor receptors. Since individual membrane receptors are expressed in only half of male breast cancers, a panel of membrane markers will be required for molecular imaging strategies to reach sensitivity. A potential panel of markers for molecular imaging, consisting of EGFR, IGF1-R, FGFR2, CD44v6, CAXII, GLUT1, and CD44v6 was positive in 77% of male breast cancers, comparable to female breast cancers.ConclusionsExpression patterns of growth factor receptors and hypoxia membrane proteins in male breast cancer are different from female breast cancer. For molecular imaging strategies, a putative panel consisting of markers for EGFR, IGF1-R, FGFR2, GLUT1, CAXII, CD44v6 was positive in 77% of cases and might be considered for development of molecular tracers for male breast cancer.

Matrix Metalloproteinase-9 as a Potential Tumor Marker in Breast Cancer

This study aimed to detect the comparative expression and activity of matrix metalloproteinase-9 (MMP-9) and its correlation with known pathological parameters such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) in 81 malignant breast tumors and adjacent normal breast tissues and in blood sera of these patients from different clinical TNM stages (ductal carcinoma in situ to T4) of breast cancer. MMP-9 was highly expressed in node-positive tumors and the preoperative blood serum of patients, but MMP-9 activity was appreciably inhibited in blood serum samples collected after surgery. The mature form of MMP-9 (84 kD) was expressed only in clinical stage III tumors (T2-4). Appreciable reduction of tissue inhibitor of metalloproteinase 1, phosphorylation of epidermal growth factor receptor, and translocation of nuclear factor-κΒ suggested their possible role in MMP-9 activation in HER2-positive breast cancer Overexpression and activation of MMP-9 predicted a higher stage of hormone-sensitive ductal breast carcinoma. Downregulation of the endogenous inhibitor of MMP-9, tissue inhibitor of metalloproteinase 1, and translocation of the transcription factor nuclear factor-κΒ in tumors may have an appreciable role in the overexpression of MMP-9. However, MMP-9 activation was not correlated with expression of estrogen and progesterone receptors. Evaluation of MMP-9 expression may provide valuable information about breast cancer treatment.

Use of survivorship care plans to re-engineer breast cancer follow-up.

162 Background: Use of survivorship care plans (SCPs) was recommended by the IOM in 2005, but benefits are a subject of ongoing debate. ASCO’s Cost of Cancer Care Task Force cited use of unnecessary imaging and tumor markers in breast cancer follow up amongst the “top five” list to improve quality. Communication with breast cancer survivors about guideline based post-treatment follow-up may be improved with SCPs, however few studies have addressed measurable outcomes. We describe use of SCPs to coordinate follow-up care in a multidisciplinary practice. Methods: In 2009, our breast surgeons, medical oncologists, and nurse practitioners agreed upon guidelines for follow up of breast cancer patients, developed a Survivorship Care Program to follow active treatment and implemented use of SCPs. Prior to 2009, follow up was partly determined at physician discretion and partly patient-driven, often with both medical and surgical providers seeing patients within short spans of time. To improve access to two part-time breast surgeons, guidelines were established to shift follow-up to medical oncologists and nurse practitioners. After diagnosis, patients were given comprehensive SCPs, which included recommended follow-up visits and testing. Wait times and numbers of new surgical patients were measured before and after use of SCPs. Results: Implementation of SCPs occurred during 2009; data from time periods two years before and after SCPs is listed below. Wait times were measured from call to first appointment. New patients included both benign and malignant breast disease. Conclusions: SCPs were useful in re-engineering follow-up habits of clinicians, adding value to each visit and gaining acceptance from established patients regarding recommended surveillance. Patients expressed that uncertainty experienced at the end of active treatment is mitigated by remaining in an environment that can be easily transitioned back to other clinical services. SCPs contributed to reduced wait times and increase in volume of new patients seen by breast surgeons. Future studies should assess contribution of SCPs to reducing unnecessary tests and improving compliance with ASCO guidelines. [Table: see text]

Does Breast Tumor Heterogeneity Necessitate Further Immunohistochemical Staining on Surgical Specimens?

Prognostic and predictive tumor markers in breast cancer are most commonly performed on core needle biopsies (CNB) of the primary tumor. Because treatment recommendations are influenced by these markers, it is imperative to verify strong concordance between tumor markers on CNB specimens and the corresponding surgical specimens (SS). A prospective study was performed on 165 women (205 samples) with breast cancer diagnosed from January 2009 to July 2011. Tumor type, grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki67 expression by immunohistochemical (IHC) testing were retrospectively analyzed in the CNB and SS. Contingency tables and agreement modeling were performed. There was substantial agreement between the CNB and SS for PR% and HER2; moderate agreement for tumor type, grade, and ER%; and fair agreement for Ki67%. In 8% of patients (n = 13), tumor heterogeneity was seen. In heterogeneous tumors the overall concordance between the CNB and SS was worse, especially for HER2. Six of these patients had areas of tumor that were positive for HER2, which were not detected in their CNBs. Nine patients had multiple distinct molecular subtypes within their tumor(s). The heterogeneous distribution of antigens in breast cancer tumors raises concern that the CNB may not adequately represent the true biologic profile in all patients. There is strong concordance for tumor type, ER, and PR between CNB and SS (although a quantitative decline was noted from CNB to SS); however, HER2 activity does not appear to be adequately detected on CNB in patients with heterogeneous tumors. These data suggest that IHC testing on the CNB alone may not be adequate to tailor targeted therapy in all patients.

CA 15-3 (Mucin-1) and Physiological Characteristics of Breast Cancer from Lahore, Pakistan

High incidence of breast cancer and its fatal effect has reached an alarming stage across the globe, including the third world countries. Many factors have been reported to be associated with the development of breast cancer but detailed structural and functional information is missing. CA 15-3 is one of the known potential tumor marker of breast cancer; however little is known about structure and functional site of this protein. Present study aims to investigate the functional role of CA 15-3 in breast cancer, especially in development and metastasis. Hundred female breast cancer patients confirmed by histopathological reports were included in the study. Their physiological characters were recorded in a performa. Enzyme linked immunosorbent assay (ELISA) technique was used to estimate serum CA 15-3 level. Immunohistochemistry was done for estrogen (ER), progesterone (PR) and Her2/neu receptors expression. The study revealed the details of physiological characteristics of female breast cancer. Mean age was 37.72 ± 5.99 and 55.05 ± 7.28 years and serum CA 15-3 (MUC1) level was 60.47 ± 8.59 and 63.17 ± 4.58 U/ml in pre and post-menopause respectively, and both groups of women had sedentary life style. Their receptor status especially of progesterone, estrogen and HER-2/neu were positive in 50% of premenopausal women and 65% of postmenopausal women. There are multiple physiological factors promoting breast cancer. High serum CA 15-3 level and hormonal imbalance of ER, PR and Her2/neu appears to be the main cause of breast cancer. It may be possible that the functional sites of these proteins may be altered which may increase the chances of metastasis in breast cancer.

Arginase activity and nitric oxide levels may be considered as tumor markers in breast cancer

Modulatory effects of Aqueous extract from Tetracarpidium conophorum leaves on key enzymes linked to erectile dysfunction and oxidative stress-induced lipid peroxidation in penile and testicular tissuesSeun Akomolafe, Ganiyu Oboh, Tosin Olasehinde, Sunday Oyeleye, Opeyemi Ogunsuyi

Decreased serum miR-181a is a potential new tool for breast cancer screening

Breast cancer (BC) screening is important for early detection, but conventional tumor markers lack the desired sensitivity. Aberrant microRNA (miRNA) expression plays an important role in tumor formation and development. Thus, serum miRNAs represent potential BC biomarkers. microRNA-181a (miR-181a) is deregulated in many types of human cancer and is a key oncogenic regulator, but the relationship between serum miR-181a and BC diagnosis has not been investigated. This study investigated serum miR-181a levels in BC patients and healthy controls and compared the diagnostic value of serum miR-181a as a BC tumor marker with the conventional tumor markers CA153 and CEA. Serum miR-181a and miR-16 (as a control) were quantified by real-time quantitative RT-PCR in 20 plasma samples. The promising results prompted analysis of 227 additional samples. The levels of CA153 and CEA were measured using electrochemiluminescence assays. Median miR-181a levels were significantly lower in patients with BC compared to healthy controls (P=0.001). ROC analysis demonstrated the sensitivity and specificity of miR-181a for BC diagnosis at 70.7 and 59.9%, respectively, whereas the sensitivities of CA153 and CEA were 10.53 and 9.21%. As a tumor marker, serum miR-181a expressed a higher level of sensitivity [55.28% (68/123)] in the early stage of BC diagnosis (ductal carcinoma in situ, TNM I and II) than the CA153 and CEA markers (8.13 and 7.32%, respectively). There were no significant associations between miR-181a levels and other clinicopathological parameters. These results suggest that serum miR-181a may represent a novel biomarker for primary BC as well as for early stage BC diagnosis. In combination with other markers, serum miR-181a may improve the sensitivity of BC screening.

Evaluating the impact of a trial in breast cancer tumor markers: A value of research analysis.

e16524 Background: Despite not being recommended by clinical guidelines, the tumor markers carcinoembryonic antigen (CEA), cancer antigen (CA)15-3, and CA 27.29 are used by some clinicians to screen for increased risk of breast cancer recurrence. Although additional research may be warranted to evaluate the benefits and risks of breast cancer tumor marker tests, clinical trials would likely need to involve thousands of women and would take many years to complete. We conducted an analysis to assess the societal value of a prospective randomized clinical trial (RCT) for breast tumor marker testing in routine follow-up of high-risk, stage II-III breast cancer survivors Methods: We used value of information techniques to assess the benefits of reducing uncertainty of using breast cancer tumor markers. We developed a decision-analytic model of biomarker testing in addition to standard surveillance at follow-up appointments every 3-6 months for five years. Expected value of sample information (EVSI) was assessed over a range of trial sizes and assumptions. Results: The overall value of research for an RCT involving 9,000 women was $166 million (EVSI). The value of improved information characterizing the survival impact of tumor markers was $81 million, quality-of-life $38 million, and test performance $95 million. Conclusions: Our analysis indicates that substantial societal value may be gained by conducting a clinical trial evaluating the use of breast cancer tumor markers. The most important aspects of the trial in our analysis were information gained on survival improvements as well as quality-of-life parameters associated with testing and test sensitivity and specificity. Our analysis indicates that smaller randomized trials, as well as adding quality of life instruments to existing trials, retrospective, and observational trials can also generate valuable and relevant information.

The Clinical Significance of Serum Soluble Fas and p53 Protein in Breast Cancer Patients: Comparison with Serum CA 15-3

Serum sFas and p53 protein have been observed in breast cancer patients, but their clinical usefulness for diagnosis and therapy monitoring has not been clarified. The aim of this study was to compare the clinical utility of serum sFas and p53 protein with that of serum CA 15-3 as the most commonly used breast cancer tumor marker. Serum samples were taken from 35 normal healthy controls and 35 breast cancer patients before surgery, after 2 weeks of surgery and after six cycles of FAC chemotherapy. Serum sFas and p53 protein levels were measured using ELISA kits. Serum CA 15-3 levels were determined using IRMA kit. Mean Serum levels of sFas and CA 15-3 were significantly elevated while p53 protein was significantly declined in breast cancer patients than controls. Serum p53 protein showed the greatest significant area under the ROC curve (84.3%) followed by sFas (80.5%), then CA 15-3 (78%). The sensitivity, specificity and cut-off value for diagnosing breast cancer patients were 84.2%, 82.6% and 2.88 U/ml for p53 protein, 83.3%, 68.2% and 497.3 pg/ml for sFas and 45.8%, 100% and 23 U/ml for CA15-3. Surgical removal of breast resulted in a significant decline in serum sFas level with no effect on serum p53 protein and CA 15-3 levels. Six cycles of chemotherapy resulted in a significant elevation in serum sFas level with no effect on serum p53 protein and CA 15-3 levels. sFas was significantly correlated with tumor grade. It could be concluded that although serum p53 protein is superior to sFas and CA15-3 for diagnosis of breast cancer patients, only sFas is useful for monitoring the response of breast cancer patients to surgery and chemotherapy if the effect of systemic inflammatory reactions is excluded.

Breast cancer tumor markers

Breast cancer is one of the most common cancer in women, presented with a lump and skin colour change, is one of thecommonest cancer in women. A wide variety of tumor markers viz. uPA, BRCA1 & 2, Ki76, ER, PR, HER etc. are usedfor establishing carcinoma of breast but none being a proper diagnostic tool for early detection, though each one has itsown prognostic value. Though proposed but only few are used in clinical practice, research studies are still ongoing toidentify and establish new biochemical parameters/markers that can be of used not only in advanced disease, but also inearly stages of the diagnostic workup of breast cancer.

The Ubiquitin Peptidase UCHL1 Induces G0/G1 Cell Cycle Arrest and Apoptosis Through Stabilizing p53 and Is Frequently Silenced in Breast Cancer

BackgroundBreast cancer (BrCa) is a complex disease driven by aberrant gene alterations and environmental factors. Recent studies reveal that abnormal epigenetic gene regulation also plays an important role in its pathogenesis. Ubiquitin carboxyl- terminal esterase L1 (UCHL1) is a tumor suppressor silenced by promoter methylation in multiple cancers, but its role and alterations in breast tumorigenesis remain unclear.Methodology/Principal FindingsWe found that UCHL1 was frequently downregulated or silenced in breast cancer cell lines and tumor tissues, but readily expressed in normal breast tissues and mammary epithelial cells. Promoter methylation of UCHL1 was detected in 9 of 10 breast cancer cell lines (90%) and 53 of 66 (80%) primary tumors, but rarely in normal breast tissues, which was statistically correlated with advanced clinical stage and progesterone receptor status. Pharmacologic demethylation reactivated UCHL1 expression along with concomitant promoter demethylation. Ectopic expression of UCHL1 significantly suppressed the colony formation and proliferation of breast tumor cells, through inducing G0/G1 cell cycle arrest and apoptosis. Subcellular localization study showed that UCHL1 increased cytoplasmic abundance of p53. We further found that UCHL1 induced p53 accumulation and reduced MDM2 protein level, and subsequently upregulated the expression of p21, as well as cleavage of caspase3 and PARP, but not in catalytic mutant UCHL1 C90S-expressed cells.Conclusions/SignificanceUCHL1 exerts its tumor suppressive functions by inducing G0/G1cell cycle arrest and apoptosis in breast tumorigenesis, requiring its deubiquitinase activity. Its frequent silencing by promoter CpG methylation may serve as a potential tumor marker for breast cancer.