scholarly journals Discordance of PIK3CA and TP53 Mutations Between Breast Cancer Brain Metastases and Matched Primary Tumors

2021 ◽  
Author(s):  
ANNA THULIN ◽  
Carola Andersson ◽  
Elisabeth Rönnerman ◽  
Shahin Lara ◽  
Chaido Chamalidou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Quality Criteria ◽  
Matched Pairs ◽  
Primary Tumors ◽  
Targeted Next Generation Sequencing ◽  
Mutational Status ◽  
Mutational Pattern ◽  
Sequencing Quality ◽  
Breast Cancer Brain Metastases

Abstract Purpose: There is limited knowledge of the biology of breast cancer (BC) brain metastasis (BM). We primarily aimed to determine the mutations in BCBM and to compare the mutational pattern with the matched primary breast cancer (BC). Secondary aims were to determine mutations in each subgroup (Luminal, HER2+ and TNBC) of BCBM and to determine survival according to specific mutations. Patients and methods: We investigated 57 BCBMs, including 46 cases with matched primary tumors (PT) by targeted Next Generation Sequencing (NGS) using the Cancer Hotspot Panel v2 (ThermoFisher Scientific) covering 207 targeted regions in 50 cancer related genes. Subtype according to immunohistochemistry was re-evaluated. Results: NGS results fulfilling sequencing quality criteria were obtained from 52 BM and 41 PT, out of which 37 were matched pairs. Pathogenic mutations were detected in 66% of PTs (27/41), and 62% of BMs (32/52). TP53 mutations were most frequent; 49% (20/41) of PTs and 48% (25/52) in BMs, followed by PIK3CA mutations; 22% (9/42) in PTs and 25% (13/52) in BMs. Mutations in CDH1, EGFR, HRAS, RB1 CDKN2A and PTEN were detected in single pairs or single samples. Mutational pattern was discordant in 24% of matched pairs. Conclusions: We show a discordance of PIK3CA and TP53 mutations of roughly 25% indicating the need to develop methods to assess mutational status in brain metastasis where analysis of cell-free DNA from cerebrospinal fluid (CSF) has shown promising results.

scholarly journals Discordance of PIK3CA and TP53 mutations between breast cancer brain metastases and matched primary tumors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Thulin ◽  
Carola Andersson ◽  
Elisabeth Werner Rönnerman ◽  
Shahin De Lara ◽  
Chaido Chamalidou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Quality Criteria ◽  
Matched Pairs ◽  
Luminal A ◽  
Primary Tumors ◽  
Targeted Next Generation Sequencing ◽  
Mutational Status ◽  
Mutational Pattern ◽  
Breast Cancer Brain Metastases

AbstractThere is limited knowledge of the biology of breast cancer (BC) brain metastasis (BM). We primarily aimed to determine the mutations in BCBM and to compare the mutational pattern with the matched primary breast cancer (BC). Secondary aims were to determine mutations in each subgroup (Luminal A-/B-like, HER2+ and TNBC) of BCBM, and to determine survival according to specific mutations. We investigated 57 BCBMs, including 46 cases with matched primary tumors (PT) by targeted Next Generation Sequencing (NGS) using the Cancer Hotspot Panel v2 (ThermoFisher Scientific) covering 207 targeted regions in 50 cancer related genes. Subtype according to immunohistochemistry was re-evaluated. NGS results fulfilling sequencing quality criteria were obtained from 52 BM and 41 PT, out of which 37 were matched pairs. Pathogenic mutations were detected in 66% of PTs (27/41), and 62% of BMs (32/52). TP53 mutations were most frequent; 49% (20/41) of PTs and 48% (25/52) in BMs, followed by PIK3CA mutations; 22% (9/42) in PTs and 25% (13/52) in BMs. Mutations in CDH1, EGFR, HRAS, RB1 CDKN2A and PTEN were detected in single pairs or single samples. Mutational pattern was discordant in 24% of matched pairs. We show a discordance of PIK3CA and TP53 mutations of roughly 25% indicating the need to develop methods to assess mutational status in brain metastasis where analysis of cell-free DNA from cerebrospinal fluid (CSF) has shown promising results.

scholarly journals Discordance of PIK3CA and TP53 Mutations Between Breast Cancer Brain Metastases and Matched Primary Tumors

2021 ◽  
Author(s):  
ANNA THULIN ◽  
Carola Andersson ◽  
Elisabeth Rönnerman ◽  
Shahin De Lara ◽  
Chaido Chamalidou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptors ◽  
Quality Criteria ◽  
Pathogenic Mutation ◽  
Matched Pairs ◽  
Luminal A ◽  
Primary Tumors ◽  
Targeted Next Generation Sequencing ◽  
Sequencing Quality ◽  
Breast Cancer Brain Metastases

Abstract Purpose: Extensive data of mutations in breast cancer (BC) metastases has been published in recent years. However, these studies contain very few patients with brain metastasis (BM). Thus, there is limited knowledge of the biology of BCBM. We primarily aimed to compare the mutational and histological pattern of BM with matched primary breast cancer (BC). Secondary aims were to determine mutations in BMs and PT in each BC subgroup (Luminal, HER2+ and TNBC) and survival according to changed or stable mutations between PTs and BMs. Patients and methods: We investigated 57 BCBMs including 46 cases with the matched primary tumors (PT) by targeted Next Generation Sequencing (NGS) using the Cancer Hotspot Panel v2 (ThermoFisher Scientific) covering 207 targeted regions in 50 cancer related genes. BC subtype according to immunohistochemistry (estrogen- and progesterone receptors, HER2 and Ki67) was obtained by re-evaluation of available tissue from BMs and PT. Results: NGS results fulfilling sequencing quality criteria were obtained from 52 BM (91.2%) and 41 (89.1%) PT, out of which 37 were matched pairs. Pathogenic mutation was detected in 66% of PTs (27/41), and 62% of BMs (32/52). TP53 mutations were most frequent; 49% (20/41) of PTs and 48% (25/52) in BMs, followed by PIK3CA mutations; 22% (9/42) in PTs and 25% (13/52) in BMs. Mutations in CDH1, EGFR, HRAS, RB1 CDKN2A and PTEN were detected in single pairs or single samples. Mutational pattern was discordant in 24% of matched pairs. Standard BC markers was discordant in 26%, with a loss of the estrogen receptor and a change from Luminal A to other subtypes as the most common. Changes of mutations in BMs compared with PT did not influence survival after diagnose of BM (p=0.4395).Conclusions: We show a discordance of PIK3CA and TP53 mutations, as well as IHC BC subgroups in 25% of the matched pairs of BM and PT, which confirms the need for re-evaluation of mutations, as well as standard BC markers by immunohistochemistry in the BM. Since there are difficulties in obtaining tissue from BM, analysis of cell-free DNA from cerebrospinal fluid (CSF) may be a way forward.

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 33. SYSTEMATIC REVIEW AND META-ANALYSIS OF BREAST CANCER BRAIN METASTASIS AND PRIMARY TUMOR RECEPTOR EXPRESSION DISCORDANCE

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii6-ii6
Author(s):  
Rupesh Kotecha ◽  
Raees Tonse ◽  
Muni Rubens ◽  
Michael McDermott ◽  
Yazmin Odia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Brain Metastasis ◽  
Primary Tumor ◽  
Expression Profiles ◽  
Receptor Expression ◽  
Her2 Status ◽  
Tumor Subtype ◽  
Primary Tumors ◽  
Breast Cancer Brain Metastasis

Abstract BACKGROUND Discordance in hormone receptor (estrogen [ER] and progesterone [PR]) and human epidermal growth factor receptor2 (HER2) status between the primary tumor and brain metastases and its effect on tumor classification subtype switching has been described but remains understudied. METHODS Using the PRISMA guidelines, a systematic review was performed of series published prior to April 2020 of biopsied or resected breast cancer brain metastasis (BCBM) from the Medline database using the keywords “breast cancer” and “brain metastasis” combined with “estrogen receptor/ER,” “progesterone receptor/PR,” “HER2/neu,” and “receptor conversion/dis- or concordance.” Weighted random effects models were used to calculate pooled estimates. RESULTS Fifteen full-text articles met inclusion criteria and cumulatively reported on 1373 patients who underwent biopsy or resection of at least one BCBM to compare to their primary tumor. At initial diagnosis, receptor expression profiles were 45.0% ER+, 41.0% ER-, 31.0% PR+, 51.0% PR-, 35% HER2+, and 47.0% HER2-. Corresponding receptor expression profiles from the BCBM were 19.0% ER+, 31.0% ER-, 13.0% PR+, 40.0% PR-, 21.0% HER2+, and 26.0% HER2-. Intra-patient receptor discordance comparisons revealed that 540 patients (42.6%) exhibited discordance in any receptor with 17.0% (95% CI: 13.0%-23.0%) discordance for ER status, 23.0% (95% CI: 18.0%-30.0%) for PR status, and 12.0% (95% CI: 8.0%-16.0%) for HER2 status. The most common receptor discordance events found in BCBM compared to primary tumors were ER loss 11.0% (95% CI: 8.0%-16.0%), PR loss 15.0% (95% CI: 11.0%-21.0%), and HER2 gain 9.0% (95% CI: 7.0%-11.0%). CONCLUSIONS BCBM commonly exhibit receptor expression changes on comparison to primary tumors including a 10% HER2 gain rate, a potential actionable target. Classification patterns need to be updated to reflect changes in overall tumor subtype grouping and which factors predict for BCBM/primary tumor discordance. Overall, tumor subtype switching and its effect on clinical management remains underappreciated.

scholarly journals Dermatopontin is differentially expressed in brain metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Microarray Data ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
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 dermatopontin, encoded by DPT, 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. We observed a significant correlation between DPT expression in primary tumors of the breast and overall survival. Molecular functions of dermatopontin may be relevant to the processes by which tumor cells of the breast metastasize to the breast. Down-regulation of DPT may be an important event for metastasis of primary tumor-derived cancer cells to the brain in humans with metastatic breast cancer.

scholarly journals MPP6 is differentially expressed in human metastatic breast cancer, in the brain and in the lymph nodes.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Microarray Data ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
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 for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that membrane protein, palmitoylated 6 (MAGUK p55 subfamily member 6), encoded by MPP6, was among the genes whose expression was most quantitatively different in the brain metastases of patients with metastatic breast cancer. MPP6 mRNA was present at decreased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of MPP6 in primary tumors was correlated with patient overall survival in patients with breast cancer. Modulation of MPP6 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain.

scholarly journals BMS1, ribosome biogenesis factor pseudogene 20, (BMS1P20) is differentially expressed in brain metastatic breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastasis ◽  
Microarray Data ◽  
Ribosome Biogenesis ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
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 BMS1, ribosome biogenesis factor pseudogene 20, encoded by BMS1P20, 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 BMS1P20 may be relevant to the processes by which tumor cells of the breast metastasize to the brain. Down-regulation of BMS1P20 may be an important event for metastasis of primary tumor-derived cancer cells to the brain in humans with metastatic breast cancer.

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