Clinical trial NCT04241237: Concordance Between Liquid and Tissue Biopsy
Official title: Concordance Between Liquid and Tissue Biopsy in Newly Diagnosed Metastatic Breast Cancer
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Breast Neoplasms
Keywords: Breast Cancer
Circulating Tumor Cells
Circulating Tumor DNA
Liquid Biopsy
Tissue biopsy
Concordance
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: Epic Sciences
name: University of Western Ontario, Canada
name: Lunenfeld Tanenbaum Research Institute
name: MOUNT SINAI HOSPITAL
name: Toronto Sunnybrook Regional Cancer Centre
name: University of Toronto
First posted: 2020-01-27
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study cohort will be selected from the Breast Cancer patients visiting London Regional Cancer Program for the treatment of their disease.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Concordance between liquid and tissue biopsy in terms of presence or absence of Cancer
timeFrame: 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 outcomes:
measure: Concordance between liquid and tissue biopsy in terms of hormone and HER2 status
timeFrame: Its a single visit study and study investigators try to have a blood draw from patients within 30 days prior to tissue biopsy.
measure: Classification of tissue biopsy results
timeFrame: Its a single visit study and study investigators try to have a blood draw from patients within 30 days prior to tissue biopsy.
measure: Exploratory analysis
timeFrame: Its a single visit study and study investigators try to have a blood draw from patients within 30 days prior to tissue biopsy.
Other outcomes:
Locations:
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
Study officials:
affiliation: London Regional Cancer Program
name: Ana Lohmann, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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