Medical Applications of Microwave Imaging

Ultrawide band (UWB) microwave imaging is a promising method for the detection of early stage breast cancer, based on the large contrast in electrical parameters between malignant tumour tissue and the surrounding normal breast-tissue. In this paper, the detection and imaging of a malignant tumour are performed through a tomographic based microwave system and signal processing. Simulations of the proposed system are performed and postimage processing is presented. Signal processing involves the extraction of tumour information from background information and then image reconstruction through the confocal method delay-and-sum algorithms. Ultimately, the revision of time-delay and the superposition of more tumour signals are applied to improve accuracy.

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T-cell receptor sequencing of early stage breast cancer tumors identifies altered clonal structure of the T-cell repertoire

10.1101/172494 ◽

2017 ◽

Author(s):

John F. Beausang ◽

Amanda J. Wheeler ◽

Natalie H. Chan ◽

Violet R. Hanft ◽

Frederick M. Dirbas ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

T Cell ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Early Stage ◽

Normal Breast ◽

Early Stage Breast Cancer ◽

Clonal Structure ◽

Cell Repertoire

Tumor infiltrating T-cells play an important role in many cancers, and can improve prognosis and yield therapeutic targets. We characterized T-cells infiltrating both breast cancer tumors and the surrounding normal breast tissue to identify T-cells specific to each, as well as their abundance in peripheral blood. Using immune profiling of the T-cell beta chain repertoire in 16 patients with early stage breast cancer, we show that the clonal structure of the tumor is significantly different from adjacent breast tissue, with the tumor containing approximately 3-fold more T-cells, but with a lower fraction of unique sequences and higher clonality compared to normal breast. The clonal structure of T-cells in blood and normal breast is more similar than between blood and tumor and can be used to distinguish tumor from normal breast tissue in 14 of 16 patients. Many T-cells overlap between tissues from the same patient, including approximately 50% of T-cells between tumor and normal breast. Both solid tissues contain high-abundance "enriched" sequences that are absent or of low abundance in the other tissue. Many of these T-cells are either not detected or detected with very low frequency in the blood, suggesting the existence of separate compartments of T-cells in both tumor and normal breast. Enriched T-cell sequences are typically unique to each patient, but there is a subset of sequences that are shared between many different patients. We show that most of these are commonly generated sequences and thus unlikely to play an important role in the tumor microenvironment.

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T cell receptor sequencing of early-stage breast cancer tumors identifies altered clonal structure of the T cell repertoire

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1713863114 ◽

2017 ◽

Vol 114 (48) ◽

pp. E10409-E10417 ◽

Cited By ~ 25

Author(s):

John F. Beausang ◽

Amanda J. Wheeler ◽

Natalie H. Chan ◽

Violet R. Hanft ◽

Frederick M. Dirbas ◽

...

Keyword(s):

Breast Cancer ◽

T Cells ◽

T Cell ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Early Stage ◽

Normal Breast ◽

Early Stage Breast Cancer ◽

Clonal Structure ◽

Cell Repertoire

Tumor-infiltrating T cells play an important role in many cancers, and can improve prognosis and yield therapeutic targets. We characterized T cells infiltrating both breast cancer tumors and the surrounding normal breast tissue to identify T cells specific to each, as well as their abundance in peripheral blood. Using immune profiling of the T cell beta-chain repertoire in 16 patients with early-stage breast cancer, we show that the clonal structure of the tumor is significantly different from adjacent breast tissue, with the tumor containing ∼2.5-fold greater density of T cells and higher clonality compared with normal breast. The clonal structure of T cells in blood and normal breast is more similar than between blood and tumor, and could be used to distinguish tumor from normal breast tissue in 14 of 16 patients. Many T cell sequences overlap between tissue and blood from the same patient, including ∼50% of T cells between tumor and normal breast. Both tumor and normal breast contain high-abundance “enriched” sequences that are absent or of low abundance in the other tissue. Many of these T cells are either not detected or detected with very low frequency in the blood, suggesting the existence of separate compartments of T cells in both tumor and normal breast. Enriched T cell sequences are typically unique to each patient, but a subset is shared between many different patients. We show that many of these are commonly generated sequences, and thus unlikely to play an important role in the tumor microenvironment.

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A pilot study to compare FXR expression in normal and malignant tissue in receptor-positive early-stage breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e14645 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e14645-e14645

Author(s):

N. Kounalakis ◽

S. Lau ◽

D. Darling ◽

M. Palomares ◽

M. Senthil ◽

...

Keyword(s):

Breast Cancer ◽

Pilot Study ◽

Normal Tissue ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Early Stage ◽

Normal Breast ◽

Invasive Cancer ◽

Malignant Tissue ◽

Non Invasive

e14645 Background: Farnesoid X receptor (FXR), a nuclear receptor, is a ligand dependent transcriptional factor regulating cholesterol and carbohydrate metabolism. Recently, FXR was shown to have a contributing role in colorectal cancer. We hypothesize that FXR expression changes from normal to premalignant to malignant tissue in patients with breast cancer. Methods: We identified 16 paired formaldehyde fixed, paraffin embedded tissue (normal, premalignant, and malignant) from patients with receptor positive, early stage breast cancer. Clinical information was extracted from a prospective database initiated in 2006 under institutional approval. Immunohistochemical staining of FXR using a validated polyclonal antibody was completed with appropriate positive and negative controls. The slides were graded independently by two investigators using an agreed upon scale to detect the percentage of positively stained cells to the nearest 10th percentile. Statistical analysis was performed by ANOVA and Student's t-test. A p-value of 0.05 was considered significant in all analyses. Results: Normal tissue and invasive cancer was identified in all 16 patient specimens. Of the 16 invasive cancers, 12 were ductal and 4 were lobular. 8/16 (50%) of the specimens also contained non-invasive cancer. 5/16 patients (31%) had N1 disease. FXR expression did not correlate with grade, histology, stage, or lymph node status. However, FXR expression increases with malignant transformation of the breast cancer cell. The mean percentage of cells staining positive for FXR in normal breast tissue was 58%, non-invasive 72% and invasive 79%. FXR staining in normal breast tissue was significantly less when compared to both invasive and noninvasive cancer (p< 0.007). Conclusions: FXR expression is upregulated in breast cancer when compared with expression in normal tissue and appears to progressively increase along the continuum of malignancy. Our pilot study results warrant further evaluation into FXR as a predictive biomarker for breast cancer, given the ability to target FXR via development of non-toxic oral ligands. No significant financial relationships to disclose.

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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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Hormone Receptor Expression Variations in Normal Breast Tissue: Preliminary Results of a Prospective Observational Study

Journal of Personalized Medicine ◽

10.3390/jpm11050387 ◽

2021 ◽

Vol 11 (5) ◽

pp. 387

Author(s):

Giacomo Santandrea ◽

Chiara Bellarosa ◽

Dino Gibertoni ◽

Maria C. Cucchi ◽

Alejandro M. Sanchez ◽

...

Keyword(s):

Hormone Receptor ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Normal Breast ◽

Receptor Expression ◽

Hormonal Stimulation ◽

Tissue Samples ◽

Hormonal Receptor ◽

Hormone Receptor Expression ◽

Cystic Disease Fluid Protein

Normal breast tissue undergoes great variations during a woman’s life as a consequence of the different hormonal stimulation. The purpose of the present study was to examine the hormonal receptor expression variations according to age, menstrual cycle, menopausal state and body mass index. To this purpose, 49 tissue samples of normal breast tissue, obtained during surgery performed for benign and malignant conditions, were immunostained with Estrogen (ER), Progesterone (PR) and Androgen receptors (AR). In addition, Ki67 and Gross Cystic Disease Fluid Protein were studied. The data obtained revealed a great variability of hormone receptor expression. ER and AR generally increased in older and post-menopausal women, while young women presented a higher proliferative rate, evaluated with Ki67. PR increase was observed in women with BMI higher than 25. The different hormonal receptor expression could favor the development of breast cancer.

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Expression of c-kit protein in cancer versus normal breast tissue

Współczesna Onkologia ◽

10.5114/wo.2012.30058 ◽

2012 ◽

Vol 4 ◽

pp. 306-309 ◽

Cited By ~ 1

Author(s):

Abdolhassan Talaiezadeh ◽

Seyed Nematollah Jazayeri ◽

Jamal Nateghi

Keyword(s):

Breast Tissue ◽

Normal Breast Tissue ◽

Normal Breast

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The Expression Pattern of Epidermal Differentiation Marker Keratin 10 in the Normal Human Breast and Breast Cancer Cells

Journal of Histochemistry & Cytochemistry ◽

10.1369/0022155420940220 ◽

2020 ◽

Vol 68 (8) ◽

pp. 561-570

Author(s):

Jiyoung Kim ◽

René Villadsen

Keyword(s):

Breast Cancer ◽

Expression Pattern ◽

Breast Tissue ◽

Normal Breast ◽

Epidermal Differentiation ◽

Breast Cancer Patients ◽

Human Breast ◽

Normal Human Breast ◽

Differentiation Marker ◽

Breast Gland

Cells of the human breast gland express an array of keratins, of which some are used for characterizing both normal and neoplastic breast tissue. However, the expression pattern of certain keratins has yet to be detailed. Here, the expression of a differentiation marker of epidermal epithelium, keratin 10 (K10), was investigated in the human breast gland. While in normal breast tissue generally less than 1% of luminal epithelial cells expressed K10, in women >30 years of age glandular structures with K10-positive (K10pos) cells were found at higher frequency than in younger women. K10pos cells belong to a mature luminal compartment as they were negative for cKIT, positive for Ks20.8, and mostly non-cycling. In breast cancer, around 16% of primary breast carcinomas tested were positive for K10 by immunohistochemistry. Interestingly, K10pos tumor cells generally exhibit features of differentiation similar to their normal counterparts. Although this suggests that K10 is a marker of tumor differentiation, data based on gene expression analysis imply that high levels of K10 dictate a worse outcome for breast cancer patients. These findings can form the basis of future studies that should unravel which role K10 may play as a marker of breast cancer:

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Accelerated aging in normal breast tissue of women with breast cancer

Breast Cancer Research ◽

10.1186/s13058-021-01434-7 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Shoghag Panjarian ◽

Jozef Madzo ◽

Kelsey Keith ◽

Carolyn M. Slater ◽

Carmen Sapienza ◽

...

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Anomaly Detection ◽

Breast Tissue ◽

Preventive Intervention ◽

Normal Breast Tissue ◽

Accelerated Aging ◽

Normal Breast ◽

Age Related ◽

Unsupervised Anomaly Detection

Abstract Background DNA methylation alterations have similar patterns in normal aging tissue and in cancer. In this study, we investigated breast tissue-specific age-related DNA methylation alterations and used those methylation sites to identify individuals with outlier phenotypes. Outlier phenotype is identified by unsupervised anomaly detection algorithms and is defined by individuals who have normal tissue age-dependent DNA methylation levels that vary dramatically from the population mean. Methods We generated whole-genome DNA methylation profiles (GSE160233) on purified epithelial cells and used publicly available Infinium HumanMethylation 450K array datasets (TCGA, GSE88883, GSE69914, GSE101961, and GSE74214) for discovery and validation. Results We found that hypermethylation in normal breast tissue is the best predictor of hypermethylation in cancer. Using unsupervised anomaly detection approaches, we found that about 10% of the individuals (39/427) were outliers for DNA methylation from 6 DNA methylation datasets. We also found that there were significantly more outlier samples in normal-adjacent to cancer (24/139, 17.3%) than in normal samples (15/228, 5.2%). Additionally, we found significant differences between the predicted ages based on DNA methylation and the chronological ages among outliers and not-outliers. Additionally, we found that accelerated outliers (older predicted age) were more frequent in normal-adjacent to cancer (14/17, 82%) compared to normal samples from individuals without cancer (3/17, 18%). Furthermore, in matched samples, we found that the epigenome of the outliers in the pre-malignant tissue was as severely altered as in cancer. Conclusions A subset of patients with breast cancer has severely altered epigenomes which are characterized by accelerated aging in their normal-appearing tissue. In the future, these DNA methylation sites should be studied further such as in cell-free DNA to determine their potential use as biomarkers for early detection of malignant transformation and preventive intervention in breast cancer.

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Postmenopausal Dense Breasts Maintain Premenopausal Levels of GH and Insulin-like Growth Factor Binding Proteins in Vivo

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz323 ◽

2020 ◽

Vol 105 (5) ◽

pp. 1617-1628 ◽

Cited By ~ 1

Author(s):

Nina Dabrosin ◽

Charlotta Dabrosin

Keyword(s):

Postmenopausal Women ◽

Breast Density ◽

Breast Tissue ◽

Normal Breast Tissue ◽

Normal Breast ◽

Dense Breast ◽

Breast Cancers ◽

Dense Breast Tissue ◽

Dense Breasts

Abstract Context Dense breast tissue is associated with 4 to 6 times higher risk of breast cancer by poorly understood mechanisms. No preventive therapy for this high-risk group is available. After menopause, breast density decreases due to involution of the mammary gland. In dense breast tissue, this process is haltered by undetermined biological actions. Growth hormone (GH) and insulin-like binding proteins (IGFBPs) play major roles in normal mammary gland development, but their roles in maintaining breast density are unknown. Objective To reveal in vivo levels of GH, IGFBPs, and other pro-tumorigenic proteins in the extracellular microenvironment in breast cancer, in normal breast tissue with various breast density in postmenopausal women, and premenopausal breasts. We also sought to determine possible correlations between these determinants. Setting and Design Microdialysis was used to collect extracellular in vivo proteins intratumorally from breast cancers before surgery and from normal human breast tissue from premenopausal women and postmenopausal women with mammographic dense or nondense breasts. Results Estrogen receptor positive breast cancers exhibited increased extracellular GH (P < .01). Dense breasts of postmenopausal women exhibited similar levels of GH as premenopausal breasts and significantly higher levels than in nondense breasts (P < .001). Similar results were found for IGFBP-1, -2, -3, and -7 (P < .01) and for IGFBP-6 (P <.05). Strong positive correlations were revealed between GH and IGFBPs and pro-tumorigenic matrix metalloproteinases, urokinase-type plasminogen activator, Interleukin 6, Interleukin 8, and vascular endothelial growth factor in normal breast tissue. Conclusions GH pathways may be targetable for cancer prevention therapeutics in postmenopausal women with dense breast tissue.

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