Autotaxin (ATX) as a Marker for Breast Cancer

Study Overview
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Brief Summary
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Breast cancer is the leading cause of cancer death in women worldwide. According to the GLOBOCAN 2018 worldwide estimates of cancer incidence and mortality, in 2018, about 2,088,849 new cases were diagnosed and approximately 626,679 women were predicted to die from the disease . It is the leading cause of cancer related mortality, representing15% of deaths per year worldwide .

Detailed Description
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Breast cancer is the most common malignancy in females in Egypt. It accounts for 32 % of cancer in women . Breast cancer in Egypt carries an unfavorable prognosis with 29% mortality and 3.7:1 incidence to mortality ratio . Despite the rising incidence of breast cancer, the survival rates have improved in recent years due to the deep research in biological behavior of breast cancer . Although the current 5-year survival for primary breast cancer is relatively high (ranging from 80% to 92% in different populations) survival rates decrease to less than 25% when the disease becomes metastatic .These data support the need to develop more efficient strategies for preventive, intervention, evaluation of therapy, and prediction of prognosis . Autotaxin (ATX) is a glycoprotein encoded by the ENPP2 (Ectonucleotide Pyrophosphatase/Phosphodiesterase 2) gene located on chromosome 8. Identical to lysophospholipase D, ATX plays a role in the synthesis of the bioactive lipid mediator lysophosphatidate (LPA) from lysophosphatidylcholine (LPC) . LPA acts through specific G protein-coupled receptors (GPCRs) to promote cellular proliferation, migration, and survival . ATX expression was also reported higher in poorly differentiated tumors and, in independent studies, is correlated with invasiveness of cancer cells suggesting a higher metastatic potential of ATX-expressing tumors . ATX is generated from platelets, endothelial cells, fibroblasts, and adipocytes and specifically, ATX from adipocytes has an impact on plasma LPA level . Thus, adipocytes could be an important origin of ATX in tumors. Breast cancer is a human cancer that has adipocyte-rich stroma. Adipose tissue comprises 56% of non-lactating breast tissue, and 35% of lactating breast tissue . ATX-LPA signaling has been reported to be involved in angiogenesis, tumor cell invasion, and migration in breast cancer . Increased ATX expression has also been reported in various forms of cancer, such as glioblastoma, hepatocellular and thyroid carcinomas, pancreatic and hematological cancers. A large number of evidence indicate that ATX-LPA is associated with chemotherapy resistance of cancer, and in breast cancer, ATX can reverse cell apoptosis. In a mouse model, α-bromomethylene phosphonate LPA (BrP-LPA), a dual ATX and pan-LPAR( Lysophosphatidic acid receptor ) inhibitor, inhibited migration and invasion of breast cancer cell lines and suppressed primary tumor and angiogenesis in a mouse xenograft study . Since tumor and stromal cells in breast cancer express ATX-LPA signaling-related proteins, inhibition of the ATX-LPA axis could be of therapeutic importance .Therefore, further study ATX as a tumor marker in breast cancer is required.

Official Title
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Autotaxin (ATX) as a Marker for Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Diagnostic Test: Serum Autotaxin
* Radiation: chest x-ray
* Diagnostic Test: Breast ultrasound or mammography
* Diagnostic Test: Histopathological examination of breast mass specimens
* Radiation: Magnetic Resonance Imaging ( MRI) and Bone scan
* Diagnostic Test: Peripheral haemogram
* Diagnostic Test: Renal and liver functions
* Diagnostic Test: Prothrombin time and concentration
* Diagnostic Test: Cancer Antigen 15-3 (CA15-3).
* Other: Full medical history
* Other: Full clinical examination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The study will be conducted on one hundred female individuals; 80 newly diagnosed breast cancer patients before any treatment or surgical intervention and 20 apparently normal female individuals. Exclusion Criteria: Patients with any other type of malignant or benign tumors, renal failure, cardiovascular diseases and liver cirrhosis were excluded from our study. Past history of chemotherapy or surgical treatment of any malignancy. Inflammatory diseases (e.g.bronchitis) or autoimmune diseases (e.g.rheumatoid arthritis).

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group<br>80 patients with breast cancer | Diagnostic Test: Serum Autotaxin<br>* Marker<br>Radiation: chest x-ray<br>* chest x- ray will be done for the study group<br>Diagnostic Test: Breast ultrasound or mammography<br>* Breast ultrasound or mammography will be done for the study group to diagnosis of breast cancer<br>Diagnostic Test: Histopathological examination of breast mass specimens<br>* by True cut or fine needle aspiration cytology<br>Radiation: Magnetic Resonance Imaging ( MRI) and Bone scan<br>* will be done for the study group<br>Diagnostic Test: Peripheral haemogram<br>* blood sample will be taken from the patients<br>Diagnostic Test: Renal and liver functions<br>* to exclude any other morbidity<br>Diagnostic Test: Prothrombin time and concentration<br>* blood sample will be taken from the patients<br>Diagnostic Test: Cancer Antigen 15-3 (CA15-3).<br>* will be done for the 2 groups<br>Other: Full medical history<br>* full medical history will be taken from all patients<br>Other: Full clinical examination<br>* full clinical examination will be done for the patients<br>|
| Placebo Comparator: Control Group<br>20 healthy controls aged ( 19 to 69 years ) from healthy volunteers after informed consent. | Diagnostic Test: Serum Autotaxin<br>* Marker<br>Diagnostic Test: Cancer Antigen 15-3 (CA15-3).<br>* will be done for the 2 groups<br>Other: Full medical history<br>* full medical history will be taken from all patients<br>Other: Full clinical examination<br>* full clinical examination will be done for the patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To estimate the level of serum ATX as a diagnostic marker for breast cancer. | blood sample will be taken from the patients for measure of serum ATX | Baseline (before any treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To establish a cut off for serum ATX as a marker for breast cancer | blood sample will be taken from the patients for measure of serum ATX | Baseline (before any treatment) |