Early Detection of Breast Cancer

Study Overview
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Brief Summary
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The TriNetra™ Breast test is intended for use as a breast cancer screening test that evaluates Circulating Tumor Cells (CTCs) associated with breast cancer. The TriNetra™Breast test should be a useful breast cancer screening option for asymptomatic women 40 years of age and older. This pivotal study is designed to provide evidence of test performance and to demonstrate its safety in the intended use population in the USA.

Detailed Description
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This prospective, case-cohort study evaluates the sensitivity and specificity of the TriNetra™-Breast test for breast cancer (adenocarcinoma) screening in women aged 40 years and older. Approximately 700 subjects will be enrolled in one of the two non-overlapping cohorts in this study. Cohort A will enroll about 500 subjects with a standard risk of breast cancer who fulfill the enrollment criteria. Cohort B will enroll approximately 200 subjects with a mammogram result of BI-RADS 4 or 5. The results of TriNetra™ -Breast will be compared with the results of mammography. The corresponding diagnostic biopsy pathology results obtained as the standard of care will be correlated with test results to confirm the performance estimates (when indicated). Mammography will be the reference standard of evaluation of breast screening status for cohort A. Histopathology report will be the reference standard to evaluate the malignant or non-malignant clinical status for cohort B. Availability of histopathological results is mandatory for the evaluation of cohort B.

Official Title
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An Evaluation of a Circulating Tumor Cell-based Test (TriNetra™-Breast) for Breast Cancer Screening in Women Aged 40 and Above

Conditions
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Breast Neoplasms

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A). For Cohort A (500 subjects are targeted to enroll) No prior diagnosis of (any) cancer Women aged 40 years and above at the time of mammography Provision of signed informed consent Capable of providing adequate health history No co-morbidity which could impair study participation or sample collection Blood draw within sixty (60) days of performance of screening mammography A redacted/deidentified mammography report will be available and provided If any prior mammography was performed, the BI-RADS score should be 1 or 2 or 3 Willingness to accept follow-up contact every 6 months for up to 2 years. Agreeable to share any future biopsy or imaging data for a maximum of 2 years from study blood draw. B). For Cohort B (BI-RADS 4 and 5) (200 subjects are targeted to enroll) No prior diagnosis of (any) cancer Women aged 40 years and above at the time of mammography Provision of signed informed consent Current mammography indicating BI-RADS 4a,4b, 4c, or 5 Capable of providing adequate health history No co-morbidity which could impair study participation or sample collection Blood draw within sixty (60) days of mammography and prior to biopsy of the breast Yet to undergo tissue diagnostic procedure for breast lesion such as fine needle, core, or excisional biopsy A redacted/deidentified mammography report and redacted/de-identified pathology report will be available and provided Willingness to accept follow-up contact every 6 months for up to 2 years. Agreeable to share any future repeat biopsy or imaging data for a maximum of 2 years from study blood draw. C). Exclusion Criteria Prior diagnosis of (any) cancer Subjects who are receiving any investigational agent. Pregnant women are excluded from this study Breastfeeding women are excluded from this study Blood transfusion within 30 days prior to screening, Subject has any condition that in the opinion of the investigator should preclude participation in the study.

Ages Eligible for Study
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Minimum Age: 40 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 |
| --- | --- |
| BI-RADS score 1 or 2 or 3 (Cohort A)<br>Subjects with a standard risk of breast cancer aged 40 years and above at the time of mammography with the BI-RADS score 1 or 2 or 3 | |
| BI-RADS score 4 or 5 (Cohort B)<br>Subjects aged 40 years and above at the time of mammography with the BI-RADS score 4 or 5 | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint of this study is the sensitivity and specificity of TriNetra Breast for breast cancer screening in women 40 years and older, using mammography and histopathology confirmed diagnosis (when relevant) as the reference methods. | The study evaluates the clinical sensitivity and specificity of the TriNetra Breast in Mammography-Negative (BIRAD 1/2/3) and Mammography-Positive (BIRAD 4/5) Cohorts | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Positive Predictive Values (PPV) and Negative Predictive Values (NPV) | The study evaluates the PPV and NPV of the TriNetra Breast for breast cancer screening in women 40 years and older, using mammography and histopathology confirmed diagnosis (when relevant) as the reference methods. | 2 years | 
| Detection rates by TNM stage | The study evaluates the detection rates (sensitivity in %) by TNM stage for the TriNetra Breast test, using surgical pathology evaluation as a reference. | 2 years | 
| Clinical performance in dense breast findings on mammography | The study evaluates the clinical sensitivity and specificity (in %) for the TriNetra Breast test in dense breast findings on mammography | 2 years | 
| Sensitivity and specificity for ductal carcinoma in situ (DCIS) detection | The study evaluates the clinical sensitivity and specificity (in %) for the TriNetra Breast test in ductal carcinoma in situ (DCIS) detection. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Early Detection, Mammography, Circulating Tumor Cells, Cancer Screening