4–21 Histopathologic Indicators of Breast Cancer Biology: Insights From Population Mammographic Screening

Traditionally, breast cancer (BC) is divided into different subtypes defined by immunohistochemistry (IHC) according to the expression of hormone receptors and overexpression/amplification of human epidermal growth factor receptor 2 (HER2), with crucial therapeutic implications. In the last few years, the definition of different BC molecular subgroups within the IHC-defined subtypes and the identification of the important role that molecular heterogeneity can play in tumor progression and treatment resistance have inspired the search for personalized therapeutic approaches. In this scenario, translational research represents a key strategy to apply knowledge from cancer biology to the clinical setting, through the study of all the tumors “omics”, including genomics, transcriptomics, proteomics, epigenomics, and metabolomics. Importantly, the introduction of new high-throughput technologies, such as next generation sequencing (NGS) for the study of cancer genome and transcriptome, greatly amplifies the potential and the applications of translational research in the oncology field. Moreover, the introduction of new experimental approaches, such as liquid biopsy, as well as new-concept clinical trials, such as biomarker-driven adaptive studies, may represent a turning point for BC translational research. </P><P> It is likely that translational research will have in the near future a significant impact on BC care, especially by giving us the possibility to dissect the complexity of tumor cell biology and develop new personalized treatment strategies.

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Collagen molecular phenotypic switch between non-neoplastic and neoplastic canine mammary tissues

Scientific Reports ◽

10.1038/s41598-021-87380-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Masahiko Terajima ◽

Yuki Taga ◽

Becky K. Brisson ◽

Amy C. Durham ◽

Kotaro Sato ◽

...

Keyword(s):

Breast Cancer ◽

Mammary Gland ◽

Mammary Carcinoma ◽

Cancer Biology ◽

Type I Collagen ◽

Critical Role ◽

Premature Death ◽

Mammary Tissue ◽

Type I ◽

Cross Links

AbstractIn spite of major advances over the past several decades in diagnosis and treatment, breast cancer remains a global cause of morbidity and premature death for both human and veterinary patients. Due to multiple shared clinicopathological features, dogs provide an excellent model of human breast cancer, thus, a comparative oncology approach may advance our understanding of breast cancer biology and improve patient outcomes. Despite an increasing awareness of the critical role of fibrillar collagens in breast cancer biology, tumor-permissive collagen features are still ill-defined. Here, we characterize the molecular and morphological phenotypes of type I collagen in canine mammary gland tumors. Canine mammary carcinoma samples contained longer collagen fibers as well as a greater population of wider fibers compared to non-neoplastic and adenoma samples. Furthermore, the total number of collagen cross-links enriched in the stable hydroxylysine-aldehyde derived cross-links was significantly increased in neoplastic mammary gland samples compared to non-neoplastic mammary gland tissue. The mass spectrometric analyses of type I collagen revealed that in malignant mammary tumor samples, lysine residues, in particular those in the telopeptides, were markedly over-hydroxylated in comparison to non-neoplastic mammary tissue. The extent of glycosylation of hydroxylysine residues was comparable among the groups. Consistent with these data, expression levels of genes encoding lysyl hydroxylase 2 (LH2) and its molecular chaperone FK506-binding protein 65 were both significantly increased in neoplastic samples. These alterations likely lead to an increase in the LH2-mediated stable collagen cross-links in mammary carcinoma that may promote tumor cell metastasis in these patients.

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Two-month stop in mammographic screening significantly impacts on breast cancer stage at diagnosis and upfront treatment in the COVID era

ESMO Open ◽

10.1016/j.esmoop.2021.100055 ◽

2021 ◽

Vol 6 (2) ◽

pp. 100055

Author(s):

A. Toss ◽

C. Isca ◽

M. Venturelli ◽

C. Nasso ◽

G. Ficarra ◽

...

Keyword(s):

Breast Cancer ◽

Mammographic Screening ◽

Cancer Stage ◽

Stage At Diagnosis

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Relationship of mammographic densities to breast cancer risk

Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1186/s43055-021-00497-y ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Engy A. Ali ◽

Mariam Raafat

Keyword(s):

Breast Cancer ◽

Breast Density ◽

Statistical Significance ◽

Significant Risk ◽

Close Relation ◽

Mammographic Screening ◽

Mammographic Breast Density ◽

Study Results ◽

Relationship Of ◽

Mammographic Densities

Abstract Background Our goal was to find out the relation between mammographic densities and cancer of the breast according to the recent ACR classification. From the medical records of Kasereliny Hospital, 49,409 women were subjected to digital mammography for screening, of which 1500 breast cancer cases were collected. The mammographic categories of breast density were ACR-A, B, C, and D, which were detected by two senior radiologists. All radiological classifications were made using both standard mammographic views bilaterally. Two-sided tests of statistical significance were represented by all the P values. Results From 2014 to 2019, 49,409 women came for digital mammographic screening, their age ranges between 40 and 65, and all of them are included in the study. One thousand cases of breast cancer cases were radiologically and pathologically diagnosed. Different densities were arranged in descending pattern depending on the frequency of positive cases: D (13.7%), C (3.3%), B (2.7%), A (2.2%). There is positive significant risk ratio among every higher mammographic density in comparison to the lower density. Conclusion Our study results show that the risk of breast cancer is in close relation to the mammographic breast density.

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LOXL2 Inhibitors and Breast Cancer Progression

Antioxidants ◽

10.3390/antiox10020312 ◽

2021 ◽

Vol 10 (2) ◽

pp. 312

Author(s):

Sandra Ferreira ◽

Nuno Saraiva ◽

Patrícia Rijo ◽

Ana S. Fernandes

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Cancer Biology ◽

Breast Cancer Cells ◽

Lysyl Oxidase ◽

Breast Cancer Progression ◽

Special Focus ◽

Amine Oxidases ◽

Cross Link ◽

Promising Strategy

LOX (lysyl oxidase) and lysyl oxidase like-1–4 (LOXL 1–4) are amine oxidases, which catalyze cross-linking reactions of elastin and collagen in the connective tissue. These amine oxidases also allow the cross-link of collagen and elastin in the extracellular matrix of tumors, facilitating the process of cell migration and the formation of metastases. LOXL2 is of particular interest in cancer biology as it is highly expressed in some tumors. This protein also promotes oncogenic transformation and affects the proliferation of breast cancer cells. LOX and LOXL2 inhibition have thus been suggested as a promising strategy to prevent metastasis and invasion of breast cancer. BAPN (β-aminopropionitrile) was the first compound described as a LOX inhibitor and was obtained from a natural source. However, novel synthetic compounds that act as LOX/LOXL2 selective inhibitors or as dual LOX/LOX-L inhibitors have been recently developed. In this review, we describe LOX enzymes and their role in promoting cancer development and metastases, with a special focus on LOXL2 and breast cancer progression. Moreover, the recent advances in the development of LOXL2 inhibitors are also addressed. Overall, this work contextualizes and explores the importance of LOXL2 inhibition as a promising novel complementary and effective therapeutic approach for breast cancer treatment.

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Establishment and characterization of a new spontaneously immortalized ER−/PR−/HER2+ human breast cancer cell line, DHSF-BR16

Scientific Reports ◽

10.1038/s41598-021-87362-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Stefania Nobili ◽

Antonella Mannini ◽

Astrid Parenti ◽

Chiara Raggi ◽

Andrea Lapucci ◽

...

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cell Line ◽

Cancer Biology ◽

Cancer Cell Line ◽

Cancer Tissue ◽

Endoplasmic Reticulum Membrane ◽

Mcf 7

AbstractInvasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women’s health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant chemotherapy and disease-free 5-years after adjuvant chemotherapy. Primary breast cancer tissue surgically removed was classified as ER−/PR−/HER2+, and the same phenotype was maintained by DHSF-BR16 cells. We examined DHSF-BR16 cell morphology and relevant biological and molecular markers, as well as their response to anticancer drugs commonly used for breast cancer treatment. MCF-7 cells were used for comparison purposes. The DHSF-BR16 cells showed the ability to form spheroids and migrate. Furthermore, DHSF-BR16 cells showed a mixed stemness phenotype (i.e. CD44+/CD24−/low), high levels of cytokeratin 7, moderate levels of cytokeratin 8 and 18, EpCAM and E-Cadh. Transcriptome analysis showed 2071 differentially expressed genes between DHSF-BR16 and MCF-7 cells (logFC > 2, p-adj < 0.01). Several genes were highly upregulated or downregulated in the new cell line (log2 scale fold change magnitude within − 9.6 to + 12.13). A spontaneous immortalization signature, mainly represented by extracellular exosomes-, plasma membrane- and endoplasmic reticulum membrane pathways (GO database) as well as by metabolic pathways (KEGG database) was observed in DHSF-BR16 cells. Also, these cells were more resistant to anthracyclines compared with MCF-7 cells. Overall, DHSF-BR16 cell line represents a relevant model useful to investigate cancer biology, to identify both novel prognostic and drug response predictive biomarkers as well as to assess new therapeutic strategies.

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Aromatase inhibitors in breast cancer.

Endocrine Related Cancer ◽

10.1677/erc.0.0110179 ◽

2004 ◽

Vol 11 (2) ◽

pp. 179-189 ◽

Cited By ~ 62

Author(s):

P E L√∏nning

Keyword(s):

Breast Cancer ◽

Aromatase Inhibitors ◽

Cancer Biology ◽

Postmenopausal Breast Cancer ◽

Phase Iii ◽

Cross Resistance ◽

Consistent Difference ◽

Clinical Effects ◽

Endocrine Regulation

The development of aromatase inhibitors for breast cancer therapy is a result of successful translational research exploring the biochemical effects of different compounds in vivo. Studies assessing plasma oestrogen levels as well as in vivo aromatase inhibition have revealed a consistent difference with respect to biochemical efficacy between the third generation compounds (anastrozole, letrozole and exemestane) and the previous, first and second generation drugs, corresponding to the improved clinical effects of these compounds as outlined in large phase III studies. Thus, endocrine evaluation has been found to be a valid surrogate parameter for clinical efficacy. Moreover, the results from these studies have added important biological information to our understanding of endocrine regulation of breast cancer. Based on the clinical results so far, aromatase inhibitors are believed to play a key role in future adjuvant therapy of postmenopausal breast cancer patients and potentially also for breast cancer prevention. Interesting findings such as the lack of cross-resistance between steroidal and non-steroidal compounds should be further explored, as this may add additional information to our understanding of breast cancer biology.

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