In Vitro Study of the Liquid Biopsy Test System of the Diagnostic Value, in Women With Various Forms of Breast Cancer

Study Overview
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Brief Summary
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The Study Objective is to evaluate the diagnostic efficacy of the liquid biopsy system versus the gold standard mammography (or MRI, or Ultrasound) diagnosis in patients with suspected breast cancer.

Detailed Description
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Women of the required age group, in case of suspicion of breast cancer, are sent to clarify the diagnosis for mammography or ultrasound of the mammary glands, or MRI. Based on the results of these studies, a biopsy is prescribed to make a final diagnosis. Before a biopsy to diagnose the presence / absence of breast cancer, patients do the blood sampling one time. The blood is processed in the Sponsor's laboratory. The test results are compared with the data obtained from the biopsy. The evaluation of the effectiveness of the method will be determined on the basis of the obtained data on the sensitivity and specificity of the test in relation to the reference method.

Official Title
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An International Multicenter Blind Comparative Controlled in Vitro Study of the Liquid Biopsy Test System of the Diagnostic Value, in Women With Various Forms of Breast Cancer in Comparison With Other Early Diagnostic Methods (Mammography/Ultrasound/MRI).

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Diagnostic Test: ARNA Breast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Availability of signed and dated informed consent. Women from 35 to 65 years old, who are generally healthy, with suspected breast cancer. Or without suspicion of (control group) Presence of a documented referral diagnosis of breast cancer Presence of a documented biopsy referral Presence of mammography, ultrasound or MRI of the mammary glands no later than three months. Exclusion Criteria: Pregnancy. Any other cancers diagnosed now or previously, with the exception of breast cancer. Therapy with cytostatics during the last three months. Chemotherapy within the past three months. Therapy with hormonal drugs, including all forms of contraceptive drugs. Therapy with other prohibited groups of drugs. Systolic blood pressure > 180 mm Hg. and / or diastolic blood pressure > 120 mm Hg. with repeated measurements. Simultaneous participation in another clinical study. Relative affiliation to the clinic, for example, the patient is a close relative of the researcher or a dependent person (for example, a clinic employee or student or a sponsor employee). A clinically significant condition or laboratory result that, in the opinion of the investigator, threatens the safety of the test subject, may interfere with assessments, or prevent the completion of the study. Failure to cooperate to participate in planned procedures, including the following examples: lack of understanding of language, mental illness, inability to visit the clinic. Diseases or conditions that may affect the conduct of the study or the interpretation of the results. History of organ transplantation. Blood transfusions within the last 6 months.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 65 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Women in age 35 to 65 with suspected breast cancer<br>Women in age 35 to 65 with suspected breast cancer, previously untreated. Additionally, eligible patients should have appropriate mammography results, either breast ultrasound or breast MRI. | Diagnostic Test: ARNA Breast<br>* Women of the required age group, in case of suspicion of breast cancer, are sent to clarify the diagnosis for mammography or ultrasound of the mammary glands, or MRI. Based on the results of these studies, a biopsy is prescribed to make a final diagnosis. Before a biopsy to diagnose the presence / absence of breast cancer, patients do the blood sampling one time. The blood is processed in the Sponsor's laboratory. The test results are compared with the data obtained from the biopsy. The evaluation of the effectiveness of the method will be determined on the basis of the obtained data on the sensitivity and specificity of the test in relation to the reference method<br>|
| Healthy Volunteers<br>Healthy woman in age 35 to 65. | Diagnostic Test: ARNA Breast<br>* Women of the required age group, in case of suspicion of breast cancer, are sent to clarify the diagnosis for mammography or ultrasound of the mammary glands, or MRI. Based on the results of these studies, a biopsy is prescribed to make a final diagnosis. Before a biopsy to diagnose the presence / absence of breast cancer, patients do the blood sampling one time. The blood is processed in the Sponsor's laboratory. The test results are compared with the data obtained from the biopsy. The evaluation of the effectiveness of the method will be determined on the basis of the obtained data on the sensitivity and specificity of the test in relation to the reference method<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of woman with positive ARNA Breast test confirmed by biopsy (Sensitivity) | Primary Measured Values for Efficiency Assessment: the absolute total number of matches between the results of the test system and mammography based on histological confirmation of the diagnosis; the sensitivity of the test by groups, particularly: the ratio of the number of true-positive test results to the total number of patients in the group with the presence of a character; the specificity of the test by groups, particularly: the ratio of the number of true-negative test results to the total number of patients in the group with no character. A group of samples from patients with a confirmed diagnosis of breast cancer will be divided into 4 subgroups depending on the biological subtype of cancer identified on the basis of IHC analysis (luminal A, luminal B, HER2/neu, triple negative), also for the subgroups obtained the primary measured values will be calculated to identify these quantities based on the biological subtype of breast cancer. | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficiency Evaluation | Estimation of the area under ROC-curve (AUC) | through study completion, an average of 1 year | 
| Relationship between test results and the age | Determination of a statistically significant relationship between test results and the age of patients at the time of testing | through study completion, an average of 1 year | 
| Positive predictive value | The ratio of true-positive test results to the total number of positive test results h) the ratio of true negative test results to the total number of negative test results (negative predictive value) i) Positive and negative likelihood ratio | through study completion, an average of 1 year | 
| Negative predictive value | The ratio of true negative test results to the total number of negative test results | through study completion, an average of 1 year |