Utility of Different Immunohistochemical Stain for Diagnosis of Invasive Breast Cancer

Breast cancer is a malignant tumor that seriously affects females’ physical health, which is the leading cause of cancer death among Chinese female. Estimating early diagnostic and prognostic markers are helpful to conduct treatment for patients with breast cancer. Accumulating investigations focused on the role of Jab1 and S100A8 proteins in the development and metastasis. In our study, we performed the immunohistochemical stain for Jab1 and S100A8 in breast carcinoma and para-carcinoma samples. We have found that the positive rate of Jab1 and S100A8 in breast cancer was higher than that in para-carcinoma tissues. The expression level of Jab1 and S100A8 in breast cancer might have a close relationship with the histologic grade and lymphatic metastasis. The two proteins might be promising supplementary targets for the treatment and prognosis of breast cancers in clinical pathology.

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The role of the clinical pharmacist in guiding adjuvant hormonal therapy in patients with breast cancer

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211029361 ◽

2021 ◽

pp. 107815522110293

Author(s):

Amanda V Pirolli ◽

Tatiana Brusamarello ◽

Stella S Everton ◽

Vânia M S Andrzejevski

Keyword(s):

Breast Cancer ◽

Hormone Therapy ◽

Hormonal Therapy ◽

Clinical Pharmacist ◽

Tertiary Care ◽

Structured Interview ◽

Care Hospital ◽

Adjuvant Hormonal Therapy ◽

Breast Cancers

Breast cancer is the most prevalent type of cancer among women, affecting about 2.1 million worldwide and is responsible for the highest number of cancer-related deaths among women. Approximately 80% of breast cancers express on the surface of hormone receptor cells, such as progesterone and estrogen. In these cases, Adjuvant Hormonal Therapy (AHT) is indicated for a period of five to ten years and consists of taking a daily oral pill. The two most used drugs in AHT are tamoxifen and Aromatase Inhibitors. One of the issues most faced by individuals who are subjected to long periods of treatment is the lack of medication adherence and, consequently, therapeutic inefficiency. It is believed that the monitoring by the pharmacist can contribute to the reduction of errors inherent to the medication, making the treatment more effective and improving the patient's quality of life. The present study aimed to know the perception of patients who live with breast cancer and who do AHT in relation to the educational performance of the clinical pharmacist. This is a qualitative, descriptive and exploratory study, carried out from March to October 2020, with 15 women undergoing treatment at the oncology unit of a tertiary-care hospital in south of Brazil. The data were obtained through a semi-structured interview using an instrument composed of two parts, one referring to the characterization of the participants and the other with the guiding question of the research: "How do you perceive the role of the pharmacist in relation to the guidelines for the use of adjuvant hormonal therapy?". The method of theoretical saturation was used to perform the sample closure and the thematic analysis was used to analyze the data. The participants were between 32 and 74 years old, seven were on tamoxifen therapy and eight on anastrozole, ten were on the first year of treatment, two on the second and three on the third year. The themes that emerged were: pharmacist-patient interaction as a safety factor in hormone therapy; role of the pharmacist in the development of strategies for self-management of the patients during hormone therapy; and, challenges for the pharmacist in relation to hormone therapy through continued guidance. It was evident that the pharmacist's educational action encouraged the participants to carry out the treatment in a more confident and assertive manner according to their particularities and beliefs.

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The Roles of DNA Demethylases in Triple-Negative Breast Cancer

Pharmaceuticals ◽

10.3390/ph14070628 ◽

2021 ◽

Vol 14 (7) ◽

pp. 628

Author(s):

Shoghag Panjarian ◽

Jean-Pierre J. Issa

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Tumor Suppressor Genes ◽

Hormone Receptors ◽

Triple Negative ◽

Breast Cancers ◽

Therapeutic Implications ◽

High Propensity ◽

Dna Methylation Profile

Triple-negative breast cancers (TNBCs) are very heterogenous, molecularly diverse, and are characterized by a high propensity to relapse or metastasize. Clinically, TNBC remains a diagnosis of exclusion by the lack of hormone receptors (Estrogen Receptor (ER) and Progesterone Receptor (PR)) as well as the absence of overexpression and/or amplification of HER2. DNA methylation plays an important role in breast cancer carcinogenesis and TNBCs have a distinct DNA methylation profile characterized by marked hypomethylation and lower gains of methylations compared to all other subtypes. DNA methylation is regulated by the balance of DNA methylases (DNMTs) and DNA demethylases (TETs). Here, we review the roles of TETs as context-dependent tumor-suppressor genes and/or oncogenes in solid tumors, and we discuss the current understandings of the oncogenic role of TET1 and its therapeutic implications in TNBCs.

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Role of the NUDT Enzymes in Breast Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22052267 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2267

Author(s):

Roni H. G. Wright ◽

Miguel Beato

Keyword(s):

Breast Cancer ◽

Signaling Pathways ◽

Cancer Progression ◽

Breast Cancers ◽

Metastatic Colonization ◽

Hormone Receptor Positive ◽

Aggressive Cancer ◽

Cancer Types ◽

Metastatic Process

Despite global research efforts, breast cancer remains the leading cause of cancer death in women worldwide. The majority of these deaths are due to metastasis occurring years after the initial treatment of the primary tumor and occurs at a higher frequency in hormone receptor-positive (Estrogen and Progesterone; HR+) breast cancers. We have previously described the role of NUDT5 (Nudix-linked to moiety X-5) in HR+ breast cancer progression, specifically with regards to the growth of breast cancer stem cells (BCSCs). BCSCs are known to be the initiators of epithelial-to-mesenchyme transition (EMT), metastatic colonization, and growth. Therefore, a greater understanding of the proteins and signaling pathways involved in the metastatic process may open the door for therapeutic opportunities. In this review, we discuss the role of NUDT5 and other members of the NUDT family of enzymes in breast and other cancer types. We highlight the use of global omics data based on our recent phosphoproteomic analysis of progestin signaling pathways in breast cancer cells and how this experimental approach provides insight into novel crosstalk mechanisms for stratification and drug discovery projects aiming to treat patients with aggressive cancer.

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Molecular basis of distinct oestrogen responses in endometrial and breast cancer

Endocrine Related Cancer ◽

10.1530/erc-17-0563 ◽

2019 ◽

Vol 26 (1) ◽

pp. 31-46 ◽

Cited By ~ 6

Author(s):

Eva Baxter ◽

Karolina Windloch ◽

Greg Kelly ◽

Jason S Lee ◽

Frank Gannon ◽

...

Keyword(s):

Breast Cancer ◽

Transcriptional Activation ◽

The Cancer Genome Atlas ◽

Breast Cancers ◽

Oestrogen Receptor Alpha ◽

Limited Success ◽

Cancer Genome Atlas ◽

Using Data ◽

Oestrogen Signalling

Up to 80% of endometrial and breast cancers express oestrogen receptor alpha (ERα). Unlike breast cancer, anti-oestrogen therapy has had limited success in endometrial cancer, raising the possibility that oestrogen has different effects in both cancers. We investigated the role of oestrogen in endometrial and breast cancers using data from The Cancer Genome Atlas (TCGA) in conjunction with cell line studies. Using phosphorylation of ERα (ERα-pSer118) as a marker of transcriptional activation of ERα in TCGA datasets, we found that genes associated with ERα-pSer118 were predominantly unique between tumour types and have distinct regulators. We present data on the alternative and novel roles played by SMAD3, CREB-pSer133 and particularly XBP1 in oestrogen signalling in endometrial and breast cancer.

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Considerations on the Use of Aromatase Inhibitors in Postmenopausal Women With Breast Cancer

Estrogens and Memory ◽

10.1093/oso/9780190645908.003.0023 ◽

2020 ◽

pp. 385-400

Author(s):

Jeffrey D. Blaustein

Keyword(s):

Breast Cancer ◽

Quality Of Life ◽

Cognitive Function ◽

Adverse Effects ◽

Develop Breast Cancer ◽

Laboratory Animals ◽

Breast Cancers ◽

The Brain

About 1 of every 8 women will develop breast cancer during her lifetime, and approximately 250,000 new cancer cases are expected annually as of 2017. Of those breast cancers, approximately 60% to 75% will express estrogen receptors, suggesting that estrogens are likely to promote growth of those tumors. Because the use of inhibitors of the synthesis of estrogens is the adjuvant treatment of choice for many women, it is essential that we understand the potential adverse effects on quality of life of those treatments. This review addresses the role of estrogens locally synthesized in the brain in laboratory animals and women, the effects of estrogens on cognitive function, the effects of synthesis blockers on cognitive function, and the limitations in performing experiments that will give us strong confidence in the results and conclusions.

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The Role of Galactography in the Detection of Breast Cancer

Tumori Journal ◽

10.1177/030089168807400210 ◽

1988 ◽

Vol 74 (2) ◽

pp. 177-181 ◽

Cited By ~ 18

Author(s):

Stefano Ciatto ◽

Patrizia Bravetti ◽

Daniela Berni ◽

Sandra Catarzi ◽

Simonetta Bianchi

Keyword(s):

Breast Cancer ◽

Physical Examination ◽

Benign Lesion ◽

Nipple Discharge ◽

Surgical Excision ◽

Histologic Examination ◽

Breast Cancers ◽

Bloody Nipple Discharge ◽

Low Incidence

The authors report on a series of 529 consecutive patients examined on physical examination, mammography, nipple discharge cytology and galactography. The criterion for galactography was essentially bloody nipple discharge (73% of cases). Serous nipple discharge was not considered worthy of routine galactography since it is associated with an extremely low incidence of breast cancer. Surgical excision and histologic examination of the discharging duct was performed in 200 cases. Eighteen cases of breast cancer were detected (10 infiltrating, 8 intraductal) of which 9, 6, 7 or 7 were suspected on physical examination, mammography, cytology or galactography, respectively. All combined tests suspected 13 of 18 breast cancers; 3 intraductal breast cancers were biopsied because of evidence of multiple papillomas on galactography, and 2 infiltrating breast cancers were operated because of persistent bloody nipple discharge in the absence of any other sign. No breast cancer was suspected on galactography alone. Galactography is indicated in the presence of bloody nipple discharge, and a biopsy should be performed when breast cancer or multiple papillomas are suspected. The diagnosis and excision of a single papilloma (breast cancer was never misdiagnosed as a single papilloma on galactography) is not worthwhile since a single papilloma is a benign lesion, and the benefit of its excision is still unclear.

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Cathepsin V suppresses GATA3 protein expression in luminal A breast cancer

Breast Cancer Research ◽

10.1186/s13058-020-01376-6 ◽

2020 ◽

Vol 22 (1) ◽

Author(s):

Naphannop Sereesongsaeng ◽

Sara H. McDowell ◽

James F. Burrows ◽

Christopher J. Scott ◽

Roberta E. Burden

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Cell Line ◽

Cysteine Protease ◽

Breast Cancers ◽

Gata3 Expression ◽

Er Positive ◽

Cathepsin V ◽

Gata3 Protein

Abstract Background Lysosomal cysteine protease cathepsin V has previously been shown to exhibit elevated expression in breast cancer tissue and be associated with distant metastasis. Research has also identified that cathepsin V expression is elevated in tumour tissues from numerous other malignancies, but despite this, there has been limited examination of the function of this protease in cancer. Here we investigate the role of cathepsin V in breast cancer in order to delineate the molecular mechanisms by which this protease contributes to tumourigenesis. Methods Lentiviral transductions were used to generate shRNA cell line models, with cell line validation undertaken using RQ-PCR and Western blotting. Phenotypic changes of tumour cell biology were examined using clonogenic and invasion assays. The relationship between GATA3 expression and cathepsin V was primarily analysed using Western blotting. Site-directed mutagenesis was used to generate catalytic mutant and shRNA-resistant constructs to confirm the role of cathepsin V in regulating GATA3 expression. Results We have identified that elevated cathepsin V expression is associated with reduced survival in ER-positive breast cancers. Cathepsin V regulates the expression of GATA3 in ER-positive breast cancers, through promoting its degradation via the proteasome. We have determined that depletion of cathepsin V results in elevated pAkt-1 and reduced GSK-3β expression, which rescues GATA3 from proteasomal degradation. Conclusions In this study, we have identified that cysteine protease cathepsin V can suppress GATA3 expression in ER-positive breast cancers by facilitating its turnover via the proteasome. Therefore, targeting cathepsin V may represent a potential therapeutic strategy in ER-positive breast cancers, by restoring GATA3 protein expression, which is associated with a more favourable clinical outcome.

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Expression of MALAT1 Promotes Trastuzumab Resistance in HER2 Overexpressing Breast Cancers

Cancers ◽

10.3390/cancers12071918 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1918

Author(s):

Yanyuan Wu ◽

Marianna Sarkissyan ◽

Ochanya Ogah ◽

Juri Kim ◽

Jaydutt V. Vadgama

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Akt Pathway ◽

Breast Cancers ◽

Trastuzumab Resistance ◽

Mesenchymal Transition ◽

Cancer Tissues

Background: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is associated with cancer progression. Our study examined the role of MALAT1 in breast cancer and the mechanisms involved in the regulation of MALAT1. Methods: In vitro cell and in vivo animal models were used to examine the role of MALAT1 in breast cancer. The interaction of FOXO1 (Forkhead Box O1) at the promoter region of MALAT1 was investigated by chromatin immunoprecipitation (ChIP) assay. Results: The data shows an elevated expression of MALAT1 in breast cancer tissues and cells compared to non-cancer tissues and cells. The highest level of MALAT1 was observed in metastatic triple-negative breast cancer and trastuzumab-resistant HER2 (human epidermal growth factor receptor 2) overexpressing (HER2+) cells. Knockdown of MALAT1 in trastuzumab-resistant HER2+ cells reversed epithelial to mesenchymal transition-like phenotype and cell invasiveness. It improved the sensitivity of the cell’s response to trastuzumab. Furthermore, activation of Akt by phosphorylation was associated with the upregulation of MALAT1. The transcription factor FOXO1 regulates the expression of MALAT1 via the PI3/Akt pathway. Conclusions: We show that MALAT1 contributes to HER2+ cell resistance to trastuzumab. Targeting the PI3/Akt pathway and stabilizing FOXO1 translocation could inhibit the upregulation of MALAT1.

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miR-489 confines uncontrolled estrogen signaling through a negative feedback mechanism and regulates tamoxifen resistance in breast cancer

10.21203/rs.3.rs-131460/v1 ◽

2020 ◽

Author(s):

Mithil Soni ◽

Ozge Saatci ◽

Yogin Patel ◽

Manikanda Raja Keerthi Raja ◽

Xinfeng Liu ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Cell Lines ◽

Tamoxifen Resistance ◽

Resistant Cell ◽

Estrogen Signaling ◽

Breast Cancers ◽

Tamoxifen Resistant ◽

Hormonal Therapies

Abstract Background Approximately 75% of diagnosed breast cancer tumors are Estrogen receptor (ER) positive tumors and are associated with better prognosis due to their response to hormonal therapies. However, around 40% of patients relapse after hormonal therapies. In the current study, we aimed to evaluate miR-489 as a novel molecular target to combat tamoxifen resistance.Methods Genomic analysis of gene expression profiles in primary breast cancers and tamoxifen resistant cell lines unveiled the potential role of miR-489 in regulation of estrogen signaling and development of tamoxifen resistance. We manipulated miR-489 expression in breast cancer cell lines by transient transfection of miR-489 mimic or establishment of knockout cell lines using the CRISPR/Cas9 system to study the reciprocal regulation of miR-489 and estrogen/ER signaling pathways. Cell proliferation, tumor sphere formation assay and flow cytometry analysis were conducted to investigate the role of miR-489 on estrogen-induced cell proliferation, cancer stem cells expansion and development of tamoxifen resistance.Results miR-489 expression was significantly downregulated in tamoxifen-resistant cell lines. Low levels of miR-489 were associated with poor clinical outcomes in patients with hormone treatment. In vitro analysis showed that loss of miR-489 expression promoted tamoxifen resistance while overexpression of miR-489 in tamoxifen-resistant cells restored tamoxifen sensitivity. Mechanistically, we found that miR-489 is an estrogen regulated miRNA that negatively regulated estrogen receptor signaling by using at least the following two mechanisms: i) modulation of ER phosphorylation status by inhibiting MAPK and AKT kinase activities; ii) regulation of nucleus to cytosol translocation of estrogen receptor α (ERα) by decreasing p38 expression and consequently ER phosphorylation. In addition, miR-489 could break the positive feed-forward loop between estrogen-ERα axis and p38 MAPK in breast cancer cells which was necessary for its function as transcription factor.Conclusion Our study unveiled the underlying molecular mechanism by which miR-489 regulates estrogen signaling pathway through a negative feedback loop and uncovered its role in the development of and overcoming tamoxifen resistance in breast cancers.

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Antibody Conjugation of Nanoparticles as Therapeutics for Breast Cancer Treatment

International Journal of Molecular Sciences ◽

10.3390/ijms21176018 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6018 ◽

Cited By ~ 2

Author(s):

Alberto Juan ◽

Francisco J. Cimas ◽

Iván Bravo ◽

Atanasio Pandiella ◽

Alberto Ocaña ◽

...

Keyword(s):

Breast Cancer ◽

Targeted Therapies ◽

Chemical Structure ◽

Breast Cancer Treatment ◽

Clinical Activity ◽

Breast Cancers ◽

High Expectations ◽

Cancer Subtypes ◽

Antibody Conjugation

Breast cancer is the most common invasive tumor in women and the second leading cause of cancer-related death. Nanomedicine raises high expectations for millions of patients as it can provide better, more efficient, and affordable healthcare, and it has the potential to develop novel therapeutics for the treatment of solid tumors. In this regard, targeted therapies can be encapsulated into nanocarriers, and these nanovehicles are guided to the tumors through conjugation with antibodies—the so-called antibody-conjugated nanoparticles (ACNPs). ACNPs can preserve the chemical structure of drugs, deliver them in a controlled manner, and reduce toxicity. As certain breast cancer subtypes and indications have limited therapeutic options, this field provides hope for the future treatment of patients with difficult to treat breast cancers. In this review, we discuss the application of ACNPs for the treatment of this disease. Given the fact that ACNPs have shown clinical activity in this clinical setting, special emphasis on the role of the nanovehicles and their translation to the clinic is placed on the revision.

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