The role of low keV virtual monochromatic imaging in increasing the conspicuity of primary breast cancer in dual-energy spectral thoracic CT examination for staging purposes

Background The additive value of dual-energy spectral computerized tomography (DESCT) in breast cancer imaging is still unknown. Purpose To investigate the role of DESCT in improving the conspicuity of primary breast cancer. Material and Methods Twenty-nine patients who were histopathologically diagnosed with breast cancer and underwent DESCT for staging of lung metastasis were evaluated retrospectively. The visual conspicuity of breast cancer was scored by two readers separately in reconstructed virtual monochromatic images obtained at 40, 60, 80, and 100 keV. A circular region of interest slightly smaller than the maximum contrasted portion of the primary breast cancer was manually placed. Iodine enhancement (HU) and iodine content (mg/mL) values of tumor, normal breast tissue and pectoral muscle, and contrast-to-noise values of images at four different energy levels were calculated. Results The lesion conspicuity score peaked at 40-keV series for both readers and was significantly higher than those at other energy levels (all P < 0.001). Lesion iodine enhancement was highest at 40-keV virtual monochromatic image reconstructions ( P < 0.001). The iodine content was significantly higher in tumor than normal breast tissue, and pectoral muscle ( P < 0.001). The highest contrast-to-noise value was obtained at 60 keV (4.0 ± 2.5), followed by 40 keV (3.9 ± 2.2), without a significant difference ( P = 0.33). Conclusion The conspicuity of primary breast cancer was significantly higher in low keV virtual monochromatic images obtained by DESCT. This gives us hope that DESCT may play an effective role in detecting incidental breast lesions. It also raises the question of whether quantitative values obtained by DESCT can be used for characterization of primary breast lesion.

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Ezrin expression in primary breast cancer, metastatic lymph nodes and normal breast tissue

Geburtshilfe und Frauenheilkunde ◽

10.1055/s-0030-1254964 ◽

2010 ◽

Vol 70 (05) ◽

Author(s):

D Gschwantler-Kaulich ◽

C Natter ◽

S Steurer ◽

I Walter ◽

C Singer

Keyword(s):

Breast Cancer ◽

Lymph Nodes ◽

Primary Breast Cancer ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Normal Breast ◽

Metastatic Lymph Nodes ◽

Metastatic Lymph ◽

Ezrin Expression

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Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions

10.21203/rs.2.16536/v3 ◽

2020 ◽

Author(s):

Toshiaki Akahane ◽

Naoki Kanomata ◽

Oi Harada ◽

Tetsumasa Yamashita ◽

Junichi Kurebayashi ◽

...

Keyword(s):

Breast Cancer ◽

Primary Tumor ◽

Primary Breast Cancer ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Metastatic Breast ◽

Normal Breast ◽

Human Breast ◽

Metastatic Lesions ◽

Generation Sequencing

Abstract Background: Next-generation sequencing (NGS) has shown that recurrent/metastatic breast cancer lesions may have additional genetic changes compared with the primary tumor. These additional changes may be related to tumor progression and/or drug resistance. However, breast cancer-targeted NGS is not still widely used in clinical practice to compare the genomic profiles of primary breast cancer and recurrent/metastatic lesions.Methods: Triplet samples of genomic DNA were extracted from each patient’s normal breast tissue, primary breast cancer, and recurrent/metastatic lesion(s). A DNA library was constructed using the QIAseq Human Breast Cancer Panel (93 genes, Qiagen) and then sequenced using MiSeq (Illumina). The Qiagen web portal was utilized for data analysis.Results: Successful results for three or four samples (normal breast tissue, primary tumor, and at least one metastatic/recurrent lesion) were obtained for 11 of 35 breast cancer patients with recurrence/metastases (36 samples). We detected shared somatic mutations in all but one patient, who had a germline mutation in TP53. Additional mutations that were detected in recurrent/metastatic lesions compared with primary tumor were in genes including TP53 (three patients) and one case each of ATR, BLM, CBFB, EP300, ERBB2, MUC16, PBRM1, and PIK3CA. Actionable mutations and/or copy number variations (CNVs) were detected in 73% (8/11) of recurrent/metastatic breast cancer lesions.Conclusions: The QIAseq Human Breast Cancer Panel assay showed that recurrent/metastatic breast cancers sometimes acquired additional mutations and CNV. Such additional genomic changes could provide therapeutic target.

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Evaluation of the expression levels of nm23-h1 mRNA in primary breast cancer, benign breast disease, axillary lymph nodes and normal breast tissue

Pathology ◽

10.1080/00313029400169122 ◽

1994 ◽

Vol 26 (4) ◽

pp. 423-428 ◽

Cited By ~ 12

Author(s):

Rebecca J. Goodall ◽

Hugh J.S. Dawkins ◽

Peter D. Robbins ◽

Erika Hähnel ◽

Mohinder Sarna ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Nodes ◽

Primary Breast Cancer ◽

Breast Tissue ◽

Benign Breast Disease ◽

Normal Breast Tissue ◽

Breast Disease ◽

Normal Breast ◽

Axillary Lymph Nodes ◽

Axillary Lymph

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Rho GTPase transcriptional activity and breast cancer risk: A Mendelian randomization analysis

10.1101/2020.12.01.20241034 ◽

2020 ◽

Author(s):

Nabila Kazmi ◽

Tim Robinson ◽

Jie Zheng ◽

Siddhartha Kar ◽

Richard M Martin ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Rho Gtpases ◽

Breast Tissue ◽

Rho Gtpase ◽

Normal Breast Tissue ◽

Normal Breast

AbstractBackgroundRho GTPases are a family of 20 intracellular signalling proteins that influence cytoskeletal dynamics, cell migration and cell cycle progression. Rho GTPases are implicated in breast cancer progression but their role in breast cancer aetiology is unknown. As aberrant Rho GTPase activity could be associated with breast cancer, we aimed to determine the potential for a causal role of Rho GTPase gene expression in breast cancer risk, using two-sample Mendelian randomization (MR).MethodsMR was undertaken in 122,977 breast cancer cases and 105,974 controls, including 69,501 estrogen receptor positive (ER+) cases and 105,974 controls, and 21,468 ER negative (ER-) cases and 105,974 controls. Single nucleotide polymorphisms (SNPs) underlying expression quantitative trait loci (eQTLs) obtained from normal breast tissue, breast cancer tissue and blood were used as genetic instruments for Rho GTPase expression. Colocalisation was performed as a sensitivity analysis to examine whether findings reflected shared causal variants or genomic confounding.ResultsWe identified genetic instruments for 14 of the 20 human Rho GTPases. Using eQTLs obtained from normal breast tissue and normal blood, we identified evidence of a causal role of RHOD in overall and ER+ breast cancers (overall breast cancer: odds ratio (OR) per standard deviation (SD) increase in expression level 1.06; (95% confidence interval (CI): 1.03, 1.09; P=5.65×10-5) and OR 1.22 (95% CI: 1.11, 1.35; P=5.22×10−5) in normal breast tissue and blood respectively). The direction of association was consistent for ER- breast cancer, although the effect-estimate was imprecisely estimated. Using eQTLs from breast cancer tissue and normal blood there was some evidence that CDC42 was inversely associated with overall and ER+ breast cancer risk. The evidence from colocalization analyses strongly supported the MR results particularly for RHOD.ConclusionsOur study suggests a potential causal role of increased RHOD gene expression, and a potential protective role for CDC42 gene expression, in overall and ER+ breast cancers. These finding warrant validation in independent samples and further biological investigation to assess whether they may be suitable targets for drug targeting.

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The Role of Chronic Inflammation in the Development of Breast Cancer

Cancers ◽

10.3390/cancers13153918 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3918

Author(s):

David N. Danforth

Keyword(s):

Breast Cancer ◽

Chronic Inflammation ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Tumor Infiltrating Lymphocytes ◽

Normal Breast ◽

Inflammatory Processes ◽

Infiltrating Lymphocytes ◽

Inflammatory Changes

Chronic inflammation contributes to the malignant transformation of several malignancies and is an important component of breast cancer. The role of chronic inflammation in the initiation and development of breast cancer from normal breast tissue, however, is unclear and needs to be clarified. A review of the literature was conducted to define the chronic inflammatory processes in normal breast tissue at risk for breast cancer and in breast cancer, including the role of lymphocyte and macrophage infiltrates, chronic active adipocytes and fibroblasts, and processes that may promote chronic inflammation including the microbiome and factors related to genomic abnormalities and cellular injury. The findings indicate that in healthy normal breast tissue there is systemic evidence to suggest inflammatory changes are present and associated with breast cancer risk, and adipocytes and crown-like structures in normal breast tissue may be associated with chronic inflammatory changes. The microbiome, genomic abnormalities, and cellular changes are present in healthy normal breast tissue, with the potential to elicit inflammatory changes, while infiltrating lymphocytes are uncommon in these tissues. Chronic inflammatory changes occur prominently in breast cancer tissues, with important contributions from tumor-infiltrating lymphocytes and tumor-associated macrophages, cancer-associated adipocytes and crown-like structures, and cancer-associated fibroblasts, while the microbiome and DNA damage may serve to promote inflammatory events. Together, these findings suggest that chronic inflammation may play a role in influencing the initiation, development and conduct of breast cancer, although several chronic inflammatory processes in breast tissue may occur later in breast carcinogenesis.

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Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions

BMC Cancer ◽

10.1186/s12885-020-07432-w ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Toshiaki Akahane ◽

Naoki Kanomata ◽

Oi Harada ◽

Tetsumasa Yamashita ◽

Junichi Kurebayashi ◽

...

Keyword(s):

Breast Cancer ◽

Primary Tumor ◽

Primary Breast Cancer ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Metastatic Breast ◽

Normal Breast ◽

Human Breast ◽

Metastatic Lesions ◽

Generation Sequencing

Abstract Background Next-generation sequencing (NGS) has shown that recurrent/metastatic breast cancer lesions may have additional genetic changes compared with the primary tumor. These additional changes may be related to tumor progression and/or drug resistance. However, breast cancer-targeted NGS is not still widely used in clinical practice to compare the genomic profiles of primary breast cancer and recurrent/metastatic lesions. Methods Triplet samples of genomic DNA were extracted from each patient’s normal breast tissue, primary breast cancer, and recurrent/metastatic lesion(s). A DNA library was constructed using the QIAseq Human Breast Cancer Panel (93 genes, Qiagen) and then sequenced using MiSeq (Illumina). The Qiagen web portal was utilized for data analysis. Results Successful results for three or four samples (normal breast tissue, primary tumor, and at least one metastatic/recurrent lesion) were obtained for 11 of 35 breast cancer patients with recurrence/metastases (36 samples). We detected shared somatic mutations in all but one patient, who had a germline mutation in TP53. Additional mutations that were detected in recurrent/metastatic lesions compared with primary tumor were in genes including TP53 (three patients) and one case each of ATR, BLM, CBFB, EP300, ERBB2, MUC16, PBRM1, and PIK3CA. Actionable mutations and/or copy number variations (CNVs) were detected in 73% (8/11) of recurrent/metastatic breast cancer lesions. Conclusions The QIAseq Human Breast Cancer Panel assay showed that recurrent/metastatic breast cancers sometimes acquired additional mutations and CNV. Such additional genomic changes could provide therapeutic target.

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Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions

10.21203/rs.2.16536/v5 ◽

2020 ◽

Author(s):

Toshiaki Akahane ◽

Naoki Kanomata ◽

Oi Harada ◽

Tetsumasa Yamashita ◽

Junichi Kurebayashi ◽

...

Keyword(s):

Breast Cancer ◽

Primary Tumor ◽

Primary Breast Cancer ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Metastatic Breast ◽

Normal Breast ◽

Human Breast ◽

Metastatic Lesions ◽

Generation Sequencing

Abstract Background: Next-generation sequencing (NGS) has shown that recurrent/metastatic breast cancer lesions may have additional genetic changes compared with the primary tumor. These additional changes may be related to tumor progression and/or drug resistance. However, breast cancer-targeted NGS is not still widely used in clinical practice to compare the genomic profiles of primary breast cancer and recurrent/metastatic lesions.Methods: Triplet samples of genomic DNA were extracted from each patient’s normal breast tissue, primary breast cancer, and recurrent/metastatic lesion(s). A DNA library was constructed using the QIAseq Human Breast Cancer Panel (93 genes, Qiagen) and then sequenced using MiSeq (Illumina). The Qiagen web portal was utilized for data analysis.Results: Successful results for three or four samples (normal breast tissue, primary tumor, and at least one metastatic/recurrent lesion) were obtained for 11 of 35 breast cancer patients with recurrence/metastases (36 samples). We detected shared somatic mutations in all but onepatient, who had a germline mutation in TP53. Additional mutations that were detected in recurrent/metastatic lesions compared with primary tumor were in genes including TP53 (three patients) and one case each of ATR, BLM, CBFB, EP300, ERBB2, MUC16, PBRM1, and PIK3CA. Actionable mutations and/or copy number variations (CNVs) were detected in 73% (8/11) of recurrent/metastatic breast cancer lesions.Conclusions: The QIAseq Human Breast Cancer Panel assay showed that recurrent/metastatic breast cancers sometimes acquired additional mutations and CNV. Such additional genomic changes could provide therapeutic target.

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Targeted next generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions

10.21203/rs.2.16536/v1 ◽

2019 ◽

Author(s):

Toshiaki Akahane ◽

Naoki Kanomata ◽

Oi Harada ◽

Tetsumasa Yamashita ◽

Junichi Kurebayashi ◽

...

Keyword(s):

Breast Cancer ◽

Primary Breast Cancer ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Primary Tumour ◽

Metastatic Breast ◽

Normal Breast ◽

Human Breast ◽

Metastatic Lesions ◽

Generation Sequencing

Abstract Background Next generation sequencing (NGS) has shown that recurrent/metastatic breast cancer lesions may have additional genetic changes compared with the primary tumour. These additional changes may be related to tumour progression and/or drug resistance. The breast cancer-targeted NGS, however, is not still widely used for comparing genomic profile of primary breast cancer and recurrent/metastatic lesions in clinical practice.Methods Genomic DNA was extracted from normal breast tissue, primary breast cancer, and recurrent/metastatic lesion(s) from the same patient. A DNA library was constructed using the QIAseq Human Breast Cancer Panel (93 genes, Qiagen) and then sequenced by a MiSeq (Illumina). The Qiagen web portal was utilized for data analysis.Results Of 107 breast cancer cases with recurrence/metastases, successful results for three or four samples (normal breast tissue, primary tumour, and at least one metastatic/recurrent lesion) were obtained for 11 patients (36 samples). We detected shared somatic mutations in all but one patient, who had germline mutations in TP53 and KMT2C . Additional mutations were detected in recurrent/metastatic lesions compared with primary tumour in genes including TP53 (three patients) and one case each of ATR , BLM , CBFB , EP300 , ERBB2 , MUC16 , PBRM1, and PIK3CA . More copy number variations (CNVs) was detected in distant metastases than in local recurrence ( P =0.030).Conclusions The QIAseq Human Breast Cancer Panel assay could identify driver mutations in both primary breast tumour tissue and recurrent/metastatic lesions in almost all patients. This method can assist in identifying drug-targetable mutations and CNV in metastatic breast cancers.

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Targeted next-generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions

10.21203/rs.2.16536/v4 ◽

2020 ◽

Author(s):

Toshiaki Akahane ◽

Naoki Kanomata ◽

Oi Harada ◽

Tetsumasa Yamashita ◽

Junichi Kurebayashi ◽

...

Keyword(s):

Breast Cancer ◽

Primary Tumor ◽

Primary Breast Cancer ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Metastatic Breast ◽

Normal Breast ◽

Human Breast ◽

Metastatic Lesions ◽

Generation Sequencing

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Targeted next generation sequencing assays using triplet samples of normal breast tissue, primary breast cancer, and recurrent/metastatic lesions

10.21203/rs.2.16536/v2 ◽

2020 ◽

Author(s):

Toshiaki Akahane ◽

Naoki Kanomata ◽

Oi Harada ◽

Tetsumasa Yamashita ◽

Junichi Kurebayashi ◽

...

Keyword(s):

Breast Cancer ◽

Primary Breast Cancer ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Primary Tumour ◽

Metastatic Breast ◽

Normal Breast ◽

Human Breast ◽

Metastatic Lesions ◽

Generation Sequencing

Abstract Background: Next generation sequencing (NGS) has shown that recurrent/metastatic breast cancer lesions may have additional genetic changes compared with the primary tumour. These additional changes may be related to tumour progression and/or drug resistance. The breast cancer-targeted NGS, however, is not still widely used for comparing genomic profile of primary breast cancer and recurrent/metastatic lesions in clinical practice.Methods: Genomic DNA was extracted from normal breast tissue, primary breast cancer, and recurrent/metastatic lesion(s) from the same patient. A DNA library was constructed using the QIAseq Human Breast Cancer Panel (93 genes, Qiagen) and then sequenced by a MiSeq (Illumina). The Qiagen web portal was utilized for data analysis.Results: Of 35 breast cancer cases with recurrence/metastases, successful results for three or four samples (normal breast tissue, primary tumour, and at least one metastatic/recurrent lesion) were obtained for 11 patients (36 samples). We detected shared somatic mutations in all but one patient, who had germline mutation in TP53. Additional mutations were detected in recurrent/metastatic lesions compared with primary tumour in genes including TP53 (three patients) and one case each of ATR, BLM, CBFB, EP300, ERBB2, MUC16, PBRM1, and PIK3CA. Actionable mutations and/or copy number variations (CNVs) were detected in 82% (9/11) of recurrent/metastatic breast cancer cases.Conclusions: The QIAseq Human Breast Cancer Panel assay could identify driver mutations in both primary breast tumour tissue and recurrent/metastatic lesions in almost all patients. This method can assist in identifying drug-targetable mutation and CNV in metastatic breast cancers.

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