Characterization & Comparison of Drugable Mutations in Primary and Metastatic Tumors, CTCs and cfDNA in MBCpatients (MIRROR)

Characterization and Comparison of Drugable Mutations in Primary Tumors, Metastatic Tissue, Circulating Tumor Cells and Cell-Free Circulating DNA in Metastatic Breast Cancer Patients

Characterization of the driver mutations in an individual metastatic breast cancer patient is critical for many reasons. Effective targeted therapies require identifying genomic alterations in the tumoral tissue. The scarce efficacy of many currently available targeted drugs may be due to the outbreak of resistant clones with different genotype that already present at the initiation of therapy. It is well known the intra-tumor heterogeneity with genetic and non-genetic factors considered as the origin of the tumor cell-clon composition. The acquisition of multiple mutations (driver and passenger), altogether with the stage of differentiation, according to the cancer stem cell hypothesis, confers to the tumor cells clinically important properties, such as resistance to therapies and seeding abilities.

Moreover, there is a current challenge in establishing whether the metastatic cells arise from the most aggressive and dominant clone in the primary tumor or the metastasic tissue diverges with substantial genetic changes very early in the evolution of the disease. Primary and metastatic tumor may have a close clonal relationship or evolve in parallel and acquire different genomic alterations. In the real life, it is plausible that both models coexist with different predominance according to the tumoral tissue and etiology.

The study hypothesizes that breast cancer metastases and primary tumors could harbor different genomic profiles related to genomic regions of interest in a clinically relevant proportion of metastatic breast cancer patients.

Moreover, the genomic aberrations found in the metastatic breast cancer tissue could also be detected in CTCs and circulating free DNA.

If true, CTCs and circulating free DNA would be convenient, non-invasive, easily accessible sources of genomic material for the analysis of mutations and other genomic aberrations.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women with metastatic breast cancer in which FFPE samples from the primary tumors are available and in whom a biopsy of the metastatic relapse is clinically indicated.

Investigators will offer enrollment to consecutively seen women who meet the entry criteria. Target enrollment is 40 patients

Description

Inclusion Criteria:

• Metastatic breast cancer confirmed by radiologic findings
• ≥ 18 years old
• Able to give signed consent
• Availability to get the paraffin block of her primary tumor.
• First metastatic relapse or tumor regrowth while on treatment for metastatic disease (progressive disease while on treatment)
• Biopsy of the metastatic site clinically indicated

Exclusion Criteria:

• Inability to get a core sample from a metastatic site
• Bone disease only (the decalcification process usually prevents an appropriate genomic study).
• Unable to drawn peripheral blood
• Unable to give the informed consent
• Coagulation disorders
• ECOG status 3-4

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cohen's kappa coefficient to measure the inter-rater agreement for mutations and other genomic findings (categorical items) between the metastatic tissue and the primary tumor tissue in Metastatic Breast Cancer patients.	26 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of somatic genomic findings (found in the primary and metastatic tumor) in circulating tumoral cells (CTC) and circulating free DNA(cfDNA) obtained from peripheral blood (liquid biopsy).		26 months
Description of the mutations in analyzed genes in the primary tumor and in CTC/cfDNA for each patient.	Note: circulating tumor cells couldn't be sequenced	26 months

Collaborators and Investigators

• Sponsor: Hospital General Universitario Gregorio Marañon
• Investigators: Study Chair: Miguel Martín, Ph, Hospital General Universitario Gregorio Maranon

Publications and helpful links

General Publications

• Gonzalez-Rivera M, Picornell AC, Alvarez EL, Martin M. A Cross-Sectional Comparison of Druggable Mutations in Primary Tumors, Metastatic Tissue, Circulating Tumor Cells, and Cell-Free Circulating DNA in Patients with Metastatic Breast Cancer: The MIRROR Study Protocol. JMIR Res Protoc. 2016 Aug 16;5(3):e167. doi: 10.2196/resprot.6024.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: October 15, 2015
• First Submitted That Met QC Criteria: December 7, 2015
• First Posted (Estimate): December 10, 2015

Study Record Updates

• Last Update Posted (Actual): August 11, 2020
• Last Update Submitted That Met QC Criteria: August 7, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: genomics; Metastatic Breast Cancer; CTCs; cfDNA; somatic mutations
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: GOMHGUGM092013

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No