Concordance Between Liquid and Tissue Biopsy

Study Overview
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Brief Summary
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Tissue biopsy is a procedure to remove a piece of tissue (sample of cells) from the body to be analyzed in a laboratory, and it is commonly performed to confirm diagnosis of a patient with symptoms of breast cancer recurrence. It may also provide information on tumor markers (hormone receptors, HER2) that can guide treatment decisions. The goal of this study is to determine whether blood tests (which require less-invasive procedures) can be used to confirm diagnosis of suspected recurrent breast cancer (as compared to tissue biopsy). Investigators plan to investigate blood factors which include circulating tumor cells (CTCs - i.e., cancer cells that can be detected in the blood), circulating tumor DNA (ctDNA - i.e., pieces of DNA from cancer cells that can be found in the blood), as well as other biomarkers. Investigators will conduct this study in 120 participants who present with suspected breast cancer recurrence and symptoms of cancer that has spread to other areas in the body. Participants will be asked for blood collection within 30 days before tissue biopsy. The tissue will be analysed locally to determine the presence of cancer and the tumor markers listed above. The blood will be processed and stored for analysis of CTCs and ctDNA. If these blood tests show concordance with tissue based tests (presence of cancer cells, hormone receptors & HER2 status), these tests could be used in future studies to confirm diagnosis using a non-invasive procedure. Also, investigators believe that the results of this study can influence other research of early-stage recurrent breast cancer.

Detailed Description
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In Canada, it is estimated that more than 26,900 women will be diagnosed with breast cancer (BC), and 5,000 women will die from BC in 2019. Metastatic BC will cause the vast majority of these deaths. Tissue biopsy is recommended to confirm recurrence (presence of cancer cells) in patients with a history of previous BC. Additionally, tissue biopsy provides information on BC subtypes (estrogen receptor (ER), progesterone receptor (PgR), and HER2 status). Technological advances over the last several years have led to more robust methods for the detection, quantification, and characterization of liquid biopsy (including CTCs and ctDNA) in recurrent BC. If these approaches demonstrate sufficiently concordant results to tissue-based testing, blood draws may quickly become a viable alternative to invasive biopsies. In a cross-sectional study, 120 consecutive individuals from study centers in Ontario, who present with highly suspicious BC distant metastases who undergo biopsy to confirm BC recurrence will be enrolled (enrollment will be continued until 100 subjects with confirmed metastatic breast cancer have been enrolled). Blood samples for the circulating factors will be taken within 30 days prior to the tissue biopsy. Patient and tumor characteristics will be recorded. At the end of study, liquid biopsy (CTCs and ctDNA) analyses will be performed blinded to biopsy results. Investigators will continuously review the number of participants in each BC subtype. Cases with tissue biopsy results not classified as definite or highly suspicious for metastatic breast cancer by the treating physician will be re-assessed after six month of study entry in an attempt to classify them as having metastatic breast cancer or not. This aims to confirm/rule out breast cancer or other diagnosis. The overall anticipated public and/or scientific benefit of the study is to demonstrate the concordance between liquid (blood) biopsy and tissue based tests in terms of the presence of cancer cells, hormone receptors, HER2 status etc. so these tests could be used in the future to confirm diagnosis using a non-invasive procedure. The results of this study will advance our understanding of liquid biomarkers and ideally improve the care journey for breast cancer patients by not subjecting them to invasive and potentially dangerous biopsy procedures.

Official Title
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Concordance Between Liquid and Tissue Biopsy in Newly Diagnosed Metastatic Breast Cancer

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Procedure: Blood Draw


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (≥18 years of age) diagnosed with primary breast cancer (BC) any subtype ER/PgR+ and HER2, triple negative or HER2+ at least 6 months before suspected metastases were identified Patients must have suspected recurrent metastatic BC that will be confirmed by tissue biopsy that is expected to yield tissue adequate for histologic examination (sampling expected to yield material for cytologic evaluation only does not satisfy this criterion) The suspected metastases must be outside the ipsilateral breast, axilla infra/supraclavicular areas. In those with suspected metastases in contralateral axilla, infra/supraclavicular areas only a new contralateral breast primary must be excluded by physical exam, mammogram and MRI Exclusion Criteria: Only locoregional recurrence (ipsilateral breast, axilla, infra/supraclavicular) suspected (see above regarding potential contralateral axillary or infra/supraclavicular metastases as only site of metastasis) Tissue biopsy occurs prior to blood collection for CTCs and ctDNA New treatment for suspected metastases commences prior to blood collection for CTCs and ctDNA Patient has received previous lines of systemic treatment for metastatic BC Previous history of an invasive non-BC apart from cancers treated with curative intent at least 5 years previously with no recurrence since diagnosis, with the exception of a non-melanoma skin cancer Patients unable or unwilling to undergo a tissue biopsy Patients unable to provide informed consent Patients undergoing only cytologic evaluation of suspected metastases

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Metastatic Breast Cancer patients<br>Investigators plan to enroll patients who are undergoing biopsy for potential metastatic Breast Cancer any subtype ER/PgR+ and HER2, triple negative or HER2+ at least 6 months before suspected metastases were identified. The suspected metastases in these patients must be outside the ipsilateral breast, axilla infra/supraclavicular areas. In those with suspected metastases in contralateral axilla, infra/supraclavicular areas only a new contralateral breast primary must be excluded by physical exam, mammogram and MRI | Procedure: Blood Draw<br>* Blood will be drawn from each patient to check the concordance between liquid and tissue biopsy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concordance between liquid and tissue biopsy in terms of presence or absence of Cancer | To analyze concordance between liquid biopsy, CTCs (Epic Sciences) and ctDNA (academic assays based on mutations and/or epigenetic changes), with biopsy results (presence or absence of cancer), and with all blood assays being conducted blinded to tissue biopsy results | Its a single visit study and the study investigators try to have a blood draw from patients within 30 days prior to tissue biopsy. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concordance between liquid and tissue biopsy in terms of hormone and HER2 status | To conduct secondary analyses of the concordance between hormone receptor and HER2 status identified on tissue specimens with those identified on CTCs (Epic Sciences). | Its a single visit study and study investigators try to have a blood draw from patients within 30 days prior to tissue biopsy. | 
| Classification of tissue biopsy results | To classify tissue biopsy results according to the interpretation of the local pathologist, the treating physician (primary comparator) and the study investigators (interpretations to include clinical data such as physical exam, radiologic investigations, blood work as available). | Its a single visit study and study investigators try to have a blood draw from patients within 30 days prior to tissue biopsy. | 
| Exploratory analysis | To conduct exploratory analyses of the associations between tumor markers and CTCs or ctDNA. | Its a single visit study and study investigators try to have a blood draw from patients within 30 days prior to tissue biopsy. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Circulating Tumor Cells, Circulating Tumor DNA, Liquid Biopsy, Tissue biopsy, Concordance