Concordance of Genomic Variants in Matched Primary Breast Cancer, Metastatic Tumor, and Circulating Tumor DNA: The MIRROR Study

2019 ◽  
pp. 1-16 ◽  
Author(s):  
Fernando Moreno ◽  
Javier Gayarre ◽  
Sara López-Tarruella ◽  
María del Monte-Millán ◽  
Antonio C. Picornell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Primary Tumor ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Circulating Tumor Dna ◽  
Primary Tumors ◽  
Genomic Variants ◽  
Ctdna Analysis ◽  
Tumor Dna

PURPOSE Genetic heterogeneity between primary tumors and their metastatic lesions has been documented in several breast cancer studies. However, the selection of therapy for patients with metastatic breast cancer and the search for biomarkers for targeted therapy are often based on findings from the primary tumor, mainly because of the difficulty of distant metastasis core biopsies. New methods for monitoring genomic changes in metastatic breast cancer are needed (ie, circulating tumor DNA [ctDNA] genomic analysis). The objectives of this study were to assess the concordance of genomic variants between primary and metastatic tumor tissues and the sensitivity of plasma ctDNA analysis to identify variants detected in tumor biopsies. PATIENTS AND METHODS Next-generation sequencing technology was used to assess the genomic mutation profile of a panel of 54 cancer genes in matched samples of primary tumor, metastatic tumor, and plasma from 40 patients with metastatic breast cancer. RESULTS Using Ion Torrent technology (ThermoFisher Scientific, Waltham, MA), we identified 110 variants that were common to the primary and metastatic tumors. ctDNA analysis had a sensitivity of 0.972 in detecting variants present in both primary and metastatic tissues. In addition, we identified 13 variants in metastatic tissue and ctDNA not present in primary tumor. CONCLUSION We identified genomic variants present in metastatic biopsies and plasma ctDNA that were not present in the primary tumor. Deep sequencing of plasma ctDNA detected most DNA variants previously identified in matched primary and metastatic tissues. ctDNA might aid in therapy selection and in the search for biomarkers for drug development in metastatic breast cancer.

scholarly journals ESR1 Gene Mutation in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer Patients: Concordance Between Tumor Tissue and Circulating Tumor DNA Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Loredana Urso ◽  
Grazia Vernaci ◽  
Jessica Carlet ◽  
Marcello Lo Mele ◽  
Matteo Fassan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hormone Receptor ◽  
Liquid Biopsy ◽  
Tumor Tissue ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Circulating Tumor Dna ◽  
Hormone Receptor Positive ◽  
Tumor Dna

Endocrine therapy represents the cornerstone of treatment in hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (mBC). The natural course of this disease is marked by endocrine resistance, mainly due to Estrogen Receptor 1 (ESR1) acquired mutations. The aim of this study is to evaluate the concordance between ESR1 status in metastatic tumor specimens and matched circulating tumor DNA (ctDNA). Forty-three patients with HR+, HER2-negative mBC underwent both a metastatic tumor biopsy and a liquid biopsy at the time of disease progression. DNA extracted from formalin fixed paraffin embedded (FFPE) tumor specimens and ctDNA from matched plasma were analyzed by droplet digital (dd)PCR for the main ESR1 mutations (Y537S, Y537C, Y537N, D538G, E380Q). We observed a total mutation rate of 21%. We found six mutations on tissue biopsy: Y537S (1), D538G (2), Y537N (1), E380Q (2). Three patients with no mutations in tumor tissue had mutations detected in ctDNA. The total concordance rate between ESR1 status on tumor tissue and plasma was 91%. Our results confirm the potential role of liquid biopsy as a non-invasive alternative to tissue biopsy for ESR1 mutation assessment in mBC patients.

scholarly journals Biglycan (BGN) is differentially expressed in metastatic breast cancer, both in metastases to the brain and to the lymph nodes.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Primary Tumor ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Differentially Expressed ◽  
Down Regulation ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that biglycan, encoded by BGN, was among the genes whose expression was most different in the brain metastases of with patients with metastatic breast cancer as compared to primary tumors of the breast. Interestingly, biglycan was also among the genes most differentially expressed transcriptome-wide when comparing primary tumors of the breast to normal breast tissue. We observed significant down-regulation of biglycan in metastasis to the brain. Molecular functions and down-regulation of BGN may be important for metastasis of primary tumor-derived cancer cells the brain in humans with metastatic breast cancer, and suggests a role for changes in biglycan expression during a spectrum of transformation from benign tissue of the breast, primary tumor and finally to metastasis of the brain.

scholarly journals CD3E is differentially expressed in metastatic breast cancer, both in metastases to the brain and to the lymph nodes.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Nodes ◽  
Primary Tumor ◽  
Immune Cell ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Down Regulation ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that the CD3 epsilon chain, a subunit of the T-cell receptor, encoded by CD3E was among the genes whose expression was most different in the metastatic tumor tissues of patients with metastatic breast cancer, both in metastases to brain and to the lymph nodes when compared to primary tumors of the breast or normal breast tissue, respectively. We observed significant down-regulation of CD3E in metastasis to the brain. If not attributable to immune cell contamination of primary tumor tissue sampled, molecular functions and down-regulation of CD3E may be important for metastasis of primary tumor-derived cancer cells to the lymph nodes and to the brain in humans with metastatic breast cancer and these data suggest some level of common origin for metastases that reside in the lymph nodes and colonize the brain.

Rab11 family-interacting protein 4, RAB11FIP4, is a differentially expressed gene in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Interacting Protein ◽  
Primary Tumors ◽  
Free Survival ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that Rab11 family-interacting protein 4, encoded by RAB11FIP4, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. RAB11FIP4 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of RAB11FIP4 in primary tumors was significantly correlated with patient recurrence-free survival and distant metastasis-free survival. Modulation of RAB11FIP4 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

scholarly journals Early, On-Treatment Levels and Dynamic Changes of Genomic Instability in Circulating Tumor DNA Predict Response to Treatment and Outcome in Metastatic Breast Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1331
Author(s):  
Adriana Aguilar-Mahecha ◽  
Josiane Lafleur ◽  
Susie Brousse ◽  
Olga Savichtcheva ◽  
Kimberly A. Holden ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Genomic Instability ◽  
Metastatic Cancer ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
T1 And T2 ◽  
Tumor Dna

Background: Circulating tumor DNA (ctDNA) offers high sensitivity and specificity in metastatic cancer. However, many ctDNA assays rely on specific mutations in recurrent genes or require the sequencing of tumor tissue, difficult to do in a metastatic disease. The purpose of this study was to define the predictive and prognostic values of the whole-genome sequencing (WGS) of ctDNA in metastatic breast cancer (MBC). Methods: Plasma from 25 patients with MBC were taken at the baseline, prior to treatment (T0), one week (T1) and two weeks (T2) after treatment initiation and subjected to low-pass WGS. DNA copy number changes were used to calculate a Genomic Instability Number (GIN). A minimum predefined GIN value of 170 indicated detectable ctDNA. GIN values were correlated with the treatment response at three and six months by Response Evaluation Criteria in Solid Tumours assessed by imaging (RECIST) criteria and with overall survival (OS). Results: GIN values were detectable (>170) in 64% of patients at the baseline and were significantly prognostic (41 vs. 18 months OS for nondetectable vs. detectable GIN). Detectable GIN values at T1 and T2 were significantly associated with poor OS. Declines in GIN at T1 and T2 of > 50% compared to the baseline were associated with three-month response and, in the case of T1, with OS. On the other hand, a rise in GIN at T2 was associated with a poor response at three months. Conclusions: Very early measurements using WGS of cell-free DNA (cfDNA) from the plasma of MBC patients provided a tumor biopsy-free approach to ctDNA measurement that was both predictive of the early tumor response at three months and prognostic.

scholarly journals The Use of Serial Circulating Tumor DNA to Detect Resistance Alterations in Progressive Metastatic Breast Cancer

2020 ◽  
Author(s):  
Saya Jacob ◽  
Andrew A. Davis ◽  
Lorenzo Gerratana ◽  
Marko Velimirovic ◽  
Ami N. Shah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Circulating Tumor Dna ◽  
Tumor Dna

scholarly journals TOM1L2 is a differentially expressed gene in human metastatic breast cancer, in the brain and in the lymph nodes.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Nodes ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Primary Tumors ◽  
Node Metastases ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that the target of myb1-like 2, encoded by TOM1L2, was among the genes whose expression was most different in the brain and lymph node metastases of patients with metastatic breast cancer. TOM1L2 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of TOM1L2 in primary tumors was significantly correlated with patient overall survival in patients with breast cancer. Modulation of TOM1L2 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain while evading immune clearance in the lymph nodes in humans with metastatic breast cancer.

scholarly journals The gastrin releasing peptide, GRP, is differentially expressed in brain metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Microarray Data ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Primary Tumors ◽  
Gastrin Releasing Peptide ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that the gastrin releasing peptide, encoded by GRP, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. Molecular functions of gastrin releasing peptide may be relevant to the processes by which tumor cells of the breast metastasize to the breast. Down-regulation of GRP may be an important event for metastasis of primary tumor-derived cancer cells to the brain in humans with metastatic breast cancer.

scholarly journals Versican (VCAN) is differentially expressed in metastatic breast cancer, both in metastases to the brain and to the lymph nodes.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Nodes ◽  
Microarray Data ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Primary Tumors ◽  
Tumor Tissues ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that the chondroitin sulfate proteoglycan versican, encoded by VCAN, was among the genes whose expression was most different in the metastatic tumor tissues of patients with metastatic breast cancer, both in metastases to brain and to the lymph nodes when compared to primary tumors of the breast. Molecular functions (6-9) and down-regulation of VCAN may be important for metastasis of primary tumor-derived cancer cells to the lymph nodes and to the brain in humans with metastatic breast cancer, and suggests some level of common origin for metastases that reside in the lymph nodes and colonize the brain.

Sign in / Sign up

Export Citation Format

Share Document