AABH (aspartyl [asparaginyl] β-hydroxylase) as a serum biomarker for breast cancer.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 2-2
Author(s):  
Kiarash Moshiri

2 Background: Breast cancer accounts for 27% of female cancers. One in every eight women will develop breast cancer in their lifetime. More than 220,000 new cases of breast cancer will be diagnosed in the United States in 2020. Five-year survival rates for breast cancer are 98% for localized disease, 83% for regionally spread and 26% for distantly spread cancer. However, 25% of all metastases occur more than 5 years after the initial diagnosis and thus survival rates decrease as time goes out to 10 years due to disease recurrence. Current detection methods rely on imaging modalities, including mammography and MRI. No serum bio-markers have been approved for either breast cancer screening or monitoring for disease recurrence, yet. In asymptomatic women in remission from breast cancer the guidelines of the major oncologic organizations only suggest annual mammography for detection of new primary tumors. Methods: We have investigated the utility of aspartyl (asparaginyl) β-hydroxylase (AABH) as a serum bio-marker for cancer. AABH has been detected by immunohistochemical staining (IHC) in a broad range of cancers including breast cancer. It has been detected by IHC in > 99% of tumor specimens tested (n > 2000) but is absent in adjacent non-affected tissue, and in tissue samples from non-affected individuals. This led to the development of a sandwich ELISA that reliably measures AABH in serum. Results: In the current study we have utilized the assay to quantify AABH levels in the sera of patients diagnosed with Breast Cancer compared to women free of disease. Increased levels of AABH were found in the serum of 99% of patients with breast cancer (n = 189). In women not known to have cancer, AABH was essentially undetectable in serum (n = 65, specificity = 96%). Serum from several women currently in remission subsequent to treatment for breast cancer were also analyzed and found to be negative for AABH. Conclusions: Thus, measurement of serum AABH levels has great promise as a diagnostic tool for breast cancer with potential application in monitoring for disease recurrence. Elevated serum AABH in conjunction with mammography and MRI may greatly facilitate earlier diagnosis of both primary and recurrent Breast Cancer.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 45-45
Author(s):  
Kiarash Moshiri

45 Background: There are no serum biomarkers currently approved for the detection of lung cancer, a leading cause of cancer associated mortality world wide. More than 180,000 cases of lung cancer will be diagnosed in the United States in 2020 by other means such as by X-ray and CT scanning methods, which have inherently lower sensitivity and higher cost when compared generally to serological methods. While the five year survival for lung cancer is 15%, a survival rate of 50% can be achieved when detection is made early in individuals with localized cancer. Current detection methods, however, enable such detection in only about 18% of cases overall. Methods: A prospective serum biomarker Aspartyl (Asparaginyl) ß Hydroxylase (AABH), has been previously found to be elevated by immunohistochemical staining (IHC) in a broad range of cancers, including lung cancer. AABH was detected in > 99% of tumor specimens tested (n > 1000) but absent in adjacent tissue. The present study introduces a double monoclonal sandwich ELISA which provides detection and comparative quantification of AABH in serum of lung cancer patients vs. normal, and high-risk controls such as cigarette smokers without cancer. This is relevant since 87% of lung cancers are attributable to cigarette smoking, and associative parallels can be seen with recent reductions in rates of smoking. Results: Increased levels of serum AABH were found in 99% of patients with lung cancer (n = 192). Serum AABH was found to be undetectable in individuals not known to have cancer (n = 129, specificity = 93%). In patients with lung cancer, AABH was detectable at all stages. In a population of 50 smokers not known to have cancer, the mean serum AABH level was 0 ng/ml with 90% specificity. Conclusions: The AABH serum ELISA therefore has great promise as an additional diagnostic tool for lung cancer having the practicality and cost effectiveness of conventional serological screening. Elevated serum AABH in conjunction with CT scanning may greatly facilitate earlier diagnosis of lung cancer at a stage in which cure rates are significantly higher and thus may contribute to increased patient survival.


2005 ◽  
Vol 15 (8) ◽  
pp. 634-634
Author(s):  
S CHUANG ◽  
W CHEN ◽  
M HASHIBE ◽  
G LI ◽  
P GANZ ◽  
...  

Author(s):  
Austin K Mattox ◽  
Beibei Yang ◽  
Christopher Douville ◽  
Sheng-fu Lo ◽  
Daniel Sciubba ◽  
...  

Abstract Background Chordomas are the most common primary spinal column malignancy in the United States. The aim of this study was to determine whether chordomas may be detected by evaluating mutations in circulating tumor DNA (ctDNA). Methods 32 patients with a biopsy-confirmed diagnosis of chordoma had blood drawn pre-operatively and/or at follow up appointments. Mutations in the primary tumor were identified by whole exome sequencing and liquid biopsy by ddPCR and/or RACE-Seq was used to detect one or more of these mutations in plasma ctDNA at concurrent or later time points. Results 87.1% of patients were ctDNA positive at the time of initial blood draw (p < 0.001). Follow up blood draws in twenty of the patients suggest that ctDNA levels may reflect the clinical status of the disease. Patients with positive ctDNA levels were more likely to have greater mutant allele frequencies in their primary tumors (p = 0.004) and undergo radiotherapy (p = 0.02), and the presence of ctDNA may correlate with response to systemic chemotherapy and/or disease recurrence. Conclusions Detection of ctDNA mutations may allow for the detection and monitoring of disease progression for chordomas.


Author(s):  
Félix Essiben ◽  
Pascal Foumane ◽  
Esther JNU Meka ◽  
Michèle Tchakounté ◽  
Julius Sama Dohbit ◽  
...  

Background: Breast cancer is today a global health problem. With 1,671,149 new cases diagnosed in 2012, it is the most common female cancer in the world and accounts for 11.9% of all cancers and it affects more people than prostate cancer. In 2008, The United States statistics showed that, for all cancer that affect women before 40 years, more than 40% of them concerned the breast. The aim of this study was to describe the clinical, histopathological and therapeutic aspects of breast cancer in women under 40 years of age in Yaoundé.Methods: This was a retrospective study with data collected from 192 medical case files of women treated over a period of 12 years, from January 2004 to December 2015 at the Yaounde General Hospital and the Yaounde Gyneco-Obstetric and Pediatric Hospital. Microsoft Epi Info version 3.4.5 and SPSS version 20.0 softwares were used for data analysis.Results: From 2004 to 2015, 1489 cases of breast cancer were treated in both hospitals. Of these, 462 women were less than 40 years old, representing a proportion of 31.0%. The mean age at diagnosis was 33.5±5.0 years and 17.7% of women had a family history of breast cancer. The average time before an initial consultation was 6.7±6.6 months.  Most cases were classified as T4 (46.1%). The most common histological type was ductal carcinoma (87.4%). Grades SBR II and SBR III were predominant (76.4%). Axillary dissection (64.4%) and neoadjuvant chemotherapy (43.9%) were the main therapeutic modalities. The overall survival rate at 5 years was 51.2%. Five-year survival rates with no local recurrence and no metastatic occurrence were 35.8% and 43.2% respectively.Conclusions: Breast cancer largely affects women under the age of 40 and is often discovered late, at an advanced stage. The prognosis appears poor. Only screening could facilitate diagnosis at an early stage of the disease for better outcomes.


2020 ◽  
Author(s):  
Shahan Mamoor

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published and public microarray and gene expression data (3, 4) to discover in an unbiased manner the most striking transcriptional features of trastuzumab treatment. We identified significant differential expression of the gene encoding the Wnt pathway molecule dishevelled-3, DVL3 (5-7), in the primary tumors of breast cancer patients treated with trastuzumab. DVL3 expression in primary tumors of the breast in patients treated with trastuzumab was significantly higher than in patients not treated with trastuzumab.


2020 ◽  
Author(s):  
Shahan Mamoor

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased manner the most striking transcriptional features of trastuzumab treatment. We identified the deleted in colorectal cancer locus DCC (5, 6) as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed higher levels of DCC messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of DCC in primary tumors of the breast, demonstrating that a gene encoding for a netrin receptor, cellular machinery utilized for axon guidance in the central nervous system (5-9), is transcriptionally induced in primary tumors of the breast following treatment with trastuzumab.


2020 ◽  
Author(s):  
Shahan Mamoor

Trastuzumab (Herceptin) is a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1) utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased manner the most significant transcriptional changes associated with trastuzumab treatment. We identified myelin transcription factor 1, encoded by MYT1 among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed higher levels of MYT1 messenger RNA than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of MYT1 in primary tumors of the breast, demonstrating increased expression of a zinc finger DNA-binding protein and neuronal-specific members of the LSD1 complex with the capacity to interact with Sin3B and with functions in neurogenesis (5-9) as a direct transcriptional consequence of treatment with trastuzumab.


2001 ◽  
Vol 125 (3) ◽  
pp. 325-331
Author(s):  
Raouf E. Nakhleh ◽  
Richard J. Zarbo

Abstract Objective.—To develop breast cancer outcomes data relating pathologic tumor variables at diagnosis with clinical method of detection. Design.—Anatomic pathologists assessed 30 consecutive breast cancers at each institution, resulting in an aggregate database of 4232 breast cancers. Setting.—Hospital-based laboratories from the United States (98%), Canada, Australia, and Belgium. Participants.—One hundred ninety-nine laboratories in the 1999 College of American Pathologists Q-Probes voluntary quality improvement program. Main Outcome Measures.—Pathologic variables indicative of favorable outcomes included percentage of carcinomas detected at the in situ stage, tumors ≤1 cm in diameter, and invasive cancers with lymph nodes negative for metastases. Results.—All outcomes measures, including percent in situ carcinomas (26.9% vs 13.8%), tumor size ≤1 cm (57.8% vs 36.5%), and lymph node–negative status (77.8% vs 64%), were more favorable when tumors were detected by screening mammography (P < .001) compared to all other detection methods. Conclusions.—This study demonstrates an opportunity for pathologists to develop outcomes information of interest to health care organizations, providers, patients, and payers by integrating routine oncologic surgical pathology and clinical breast cancer detection data. Such readily obtained interim outcomes data trended and benchmarked over time can demonstrate the relative clinical efficacy of preventive breast care provided by health care systems long before mortality data are available.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10517-10517
Author(s):  
A. Rody ◽  
T. Karn ◽  
C. Solbach ◽  
R. Gaetje ◽  
R. Diallo ◽  
...  

10517 Background: Endocrine responsiveness is one of the most important characteristics of breast cancer. The negative association between expression of the estrogen receptor (ER) and proliferation detected in normal breast is frequently lost in breast cancers leading to receptor independent growth and poor patients’ prognosis. Methods: Microarray analysis of 171 breast cancer samples allowed the discrimination of a KIT+ tumor group by using a set of genes coregulated with the “stem cell factor” receptor KIT. Validation was performed on three independent datasets encompassing 637 samples. Furthermore the response to endocrine treatment only was analyzed in a dataset of 700 patients. Results: KIT+ tumors are transcriptionally related to proposed mammary stem cells. Two types of KIT+ tumors were identified which are characterized by their positive and negative ER status, respectively. The inverse link of ER expression and proliferation is perfectly conserved within the KIT+ tumor groups, while it is uncoupled among half of the KIT-Low ER positive tumors. Those “uncoupled” ER positive tumors with altered ER response are characterized by a prognosis inferior to the ER negative cancers despite an apparent positive ER status (hazard ratio for disease recurrence, 2.07; 95% CI 1.53–2.81; P<0.001). Moreover, the 5 and 10 year survival rates of lymph node negative “uncoupled” tumors are even worse than those of lymph node positive “normal” ER positive cancers. While all ER positive patients seem to profit from endocrine treatment the relative benefit was reduced in uncoupled tumors (21.2 % vs. 31.7 %). Conclusions: The classification of breast cancers according to this biologically based model identified clinical relevant tumor groups whose further characterization will have important implications. Moreover, since the ability to recognize malfunctions in ER pathways largely depends on an appropriate reference system, the KIT+ tumors could allow a dissection of estrogen responsiveness giving crucial insights for prediction of response to endocrine therapy. No significant financial relationships to disclose.


2020 ◽  
Author(s):  
Shahan Mamoor

Trastuzumab (Herceptin), a monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) (1), is utilized for the treatment of adjuvant and metastatic breast cancer (2) in the United States and worldwide. We mined published microarray and gene expression data (3, 4) to discover in an unbiased fashion the most significant transcriptional changes associated with treatment with trastuzumab in patients with breast cancer. We identified the proto-oncogene and tyrosine kinase Src as among the genes most differentially expressed in the primary tumors of patients with breast cancer treated with trastuzumab. The primary tumors of breast cancer patients treated with trastuzumab expressed higher levels of Src messenger than did patients not treated with trastuzumab, and a single administration of trastuzumab was sufficient to result in differential expression of Src in primary tumors of the breast, demonstrating that a proto-oncogene (5) and gene whose product is necessary to drive MMTV-induced tumorigenesis of the mammary gland in mice6 is transcriptionally induced in primary tumors of the breast, likely as a direct result of treatment with trastuzumab.


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