Autotaxin (ATX) as a Marker for Breast Cancer

Not Applicable

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

• Registration Number: NCT04328194
• Lead Sponsor: Assiut University

Brief Summary

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

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.

Study Timeline

• Status Verified: 2020-03
• Study First Submitted: 2020-03-28
• Study First Submitted QC: 2020-03-30
• Last Update Submitted: 2020-03-30
• Study First Posted: 2020-03-31
• Last Update Posted: 2020-03-31
• Study Start: 2021-05-01
• Primary Completion: 2022-05-01
• Study Completion: 2022-11-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 100

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control Group	Serum Autotaxin	20 healthy controls aged ( 19 to 69 years ) from healthy volunteers after informed consent.
Control Group	Cancer Antigen 15-3 (CA15-3).	20 healthy controls aged ( 19 to 69 years ) from healthy volunteers after informed consent.
Study Group	Peripheral haemogram	80 patients with breast cancer
Study Group	chest x-ray	80 patients with breast cancer
Study Group	Serum Autotaxin	80 patients with breast cancer
Study Group	Breast ultrasound or mammography	80 patients with breast cancer
Study Group	Cancer Antigen 15-3 (CA15-3).	80 patients with breast cancer
Study Group	Histopathological examination of breast mass specimens	80 patients with breast cancer
Study Group	Magnetic Resonance Imaging ( MRI) and Bone scan	80 patients with breast cancer
Study Group	Renal and liver functions	80 patients with breast cancer
Study Group	Prothrombin time and concentration	80 patients with breast cancer
Study Group	Full medical history	80 patients with breast cancer
Control Group	Full medical history	20 healthy controls aged ( 19 to 69 years ) from healthy volunteers after informed consent.
Control Group	Full clinical examination	20 healthy controls aged ( 19 to 69 years ) from healthy volunteers after informed consent.
Study Group	Full clinical examination	80 patients with breast cancer

Primary Outcome Measures

Name	Time	Method
To estimate the level of serum ATX as a diagnostic marker for breast cancer.	Baseline (before any treatment)	blood sample will be taken from the patients for measure of serum ATX

Secondary Outcome Measures

Name	Time	Method
To establish a cut off for serum ATX as a marker for breast cancer	Baseline (before any treatment)	blood sample will be taken from the patients for measure of serum ATX