Telomerase Activity and Prognosis in Primary Breast Cancers

PURPOSE: Recent studies associate telomerase activity with prognostic factors and survival. We compared quantitative telomerase activity in primary tumors with traditional prognostic factors and outcome in a group of invasive but nonmetastatic breast cancers. PATIENTS AND METHODS: Telomerase activity was measured in 203 invasive breast cancers by the quantitative telomeric repeat amplification protocol method. Telomerase expression was compared with 28S rRNA level, tumor content, and clinical variables, including outcome. For clinical correlations, telomerase activity was standardized by two methods: (1) a correction for cellularity using 28S rRNA levels, and (2) a correction for the histologically determined invasive proportion of the specimen. RESULTS: Telomerase activity was found in 82% of breast cancers with measurable 28S rRNA levels. Telomerase activity was associated with the proliferative index (P < .01) of the tumor but not with any other prognostic variable. Neither uncorrected nor corrected telomerase activity was associated with relapse-free or overall survival in this study. CONCLUSION: Telomerase activity level was associated with the proliferative index of invasive breast cancers, but its measurement in samples from this group of nonmetastatic breast cancer patients did not predict survival.

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Increased expression of the estrogen receptor alpha, ESR1, in the tumors of breast cancer patients treated with trastuzumab.

10.31219/osf.io/wrhgf ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Estrogen Receptor Alpha ◽

Estrogen Receptor Α ◽

Needle Aspiration ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Primary Tumors ◽

Transcriptional Induction ◽

Selection Of

Hormones function as growth factors, and estrogen provides growth signals to support and induce the proliferation of breast cancers (1-3). This is the basis of the use of endocrine therapies (4, 5) including tamoxifen and letrozole as first-line treatment for patients with breast cancer. We found through mining published microarray and multiplexed gene expression profiling datasets that the estrogen receptor α (ESR1) was among the genes most differentially expressed in the primary tumors and fine needle aspiration-isolated tumor cells of patients with breast cancer treated with trastuzumab. However, estrogen receptor α was expressed at higher rather than lower levels in the tumors of trastuzumab-treated patients. These data, obtained through blind, systems-level analysis of published microarray data (6-8), suggest that trastuzumab administration in patients with breast cancer is associated with transcriptional induction of the estrogen receptor or selection of tumor clones with high expression of ESR1.

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High level of EGF-R expression in carcinomatous skin invasion: Does it reflect the tissue characteristics of the breast carcinoma aggressiveness?

Archive of oncology ◽

10.2298/aoo0203111n ◽

2002 ◽

Vol 10 (3) ◽

pp. 111-114

Author(s):

Zora Neskovic-Konstantinovic ◽

Dragica Nikolic-Vukosavljevic ◽

Ksenija Kanjer ◽

Danica Jovanovic ◽

Mirjana Brankovic-Magic

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Inflammatory Breast Cancer ◽

Normal Skin ◽

Locally Advanced ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Primary Tumors ◽

Number Of Patients ◽

Cancer Aggressiveness

Background: The normal function and distribution of EGF-R and its role in breast cancer aggressiveness, prognosis and prediction, have become extremely important in the light of the recently developed methods of EGF-R targeting. In the aim to investigate the relationship between EGF-R and the aggressive tumor behavior, the EGF-R content was analyzed as related to the presence of inflammatory breast skin involvement. Methods: EGF-R, ER and PR content was determined at diagnosis, using the biochemical methods, in the group of 103 unselected breast cancer patients, either in primary tumors (TU), lymph nodes (LN) or skin tissue samples (65, 27 and 11 cases respectively). In 10 patients with inflammatory breast cancers, TU/LN tissue was sampled from 3, and skin from 7 patients. Results: ER and PR content was significantly higher in tumor and LN tissue, compared to the invaded skin the EGF-R content was, on the contrary, significantly higher in skin than in TU or LN tissue. However, no difference was found between TU and LN in all three receptors' content. When the receptor content was analyzed in 10 patients with inflammatory breast cancer, higher levels of both ER and PR were found in tumor biopsies than in skin biopsies, while for the EGF-R the result was opposite. Significantly lower ER content and a trend towards higher EGF-R content was found in the inflammatory breast cancers in comparison to the non-inflammatory ones. Conclusion: Although we examined a small number of patients, our results suggest that the EGF-R could be a marker of breast cancer aggressiveness. However, the influence of the normal skin cells contaminating the biopsied tumor tissue cannot be ruled out. The predictive role of EGF-R deserves to be further investigated especially in locally advanced inflammatory breast cancer patients.

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Blood Genome-Wide Transcriptional Profiles of HER2 Negative Breast Cancers Patients

Mediators of Inflammation ◽

10.1155/2016/3239167 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Ovidiu Balacescu ◽

Loredana Balacescu ◽

Oana Virtic ◽

Simona Visan ◽

Claudia Gherman ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Triple Negative ◽

Transcriptional Analysis ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Primary Tumors ◽

Cancer Subtypes ◽

Her2 Breast Cancer ◽

Adaptive Immune Cells

Tumors act systemically to sustain cancer progression, affecting the physiological processes in the host and triggering responses in the blood circulating cells. In this study, we explored blood transcriptional patterns of patients with two subtypes of HER2 negative breast cancers, with different prognosis and therapeutic outcome. Peripheral blood samples from seven healthy female donors and 29 women with breast cancer including 14 triple-negative breast cancers and 15 hormone-dependent breast cancers were evaluated by microarray. We also evaluated the stroma in primary tumors. Transcriptional analysis revealed distinct molecular signatures in the blood of HER2− breast cancer patients according to ER/PR status. Our data showed the implication of immune signaling in both breast cancer subtypes with an enrichment of these processes in the blood of TNBC patients. We observed a significant alteration of “chemokine signaling,” “IL-8 signaling,” and “communication between innate and adaptive immune cells” pathways in the blood of TNBC patients correlated with an increased inflammation and necrosis in their primary tumors. Overall, our data indicate that the presence of triple-negative breast cancer is associated with an enrichment of altered systemic immune-related pathways, suggesting that immunotherapy could possibly be synergistic to the chemotherapy, to improve the clinical outcome of these patients.

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Synchronous Papillary Thyroid Carcinoma and Breast Ductal Carcinoma: A Case Report

Case Reports in Clinical Practice ◽

10.18502/crcp.v6i1.5950 ◽

2021 ◽

Author(s):

Hedieh Moradi Tabriz ◽

Arezoo Eftekhar Javadi ◽

Atieh Zandnejadi ◽

Adel Yazdankhah ◽

Reza Hajebi

Keyword(s):

Breast Cancer ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Ductal Carcinoma ◽

Incidence Rates ◽

Breast Cancers ◽

Papillary Thyroid ◽

Breast Cancer Patients ◽

Cervical Lymph Nodes ◽

Primary Tumors

Breast cancer was the most frequent cause of cancer-induced death among middle-aged (20- 59) women in the last decade. In contrast, the incidence rates of thyroid cancer have begun to stabilize in recent years. The synchronous neoplasms of thyroid and breast cancers are very rare in clinical settings. The current study presented a case of synchronous Papillary Thyroid Carcinoma (PTC) and breast ductal carcinoma in a 37-year-old woman. It is proposed that the mechanism of these synchronous primary tumors is associated with an interaction between the breast and thyroid hormonal responses. It is essential to examine breast tissue in patients with thyroid carcinoma or vice versa. In our case, although axillary sentinel lymph node was free from the tumor, cervical lymph nodes were involved by breast carcinoma; suggesting the importance of cervical examination in breast cancer patients.

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Quantitative HER2 levels and steroid receptor expression in primary breast cancers and in matched brain metastases.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.603 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 603-603 ◽

Cited By ~ 1

Author(s):

Wojciech Biernat ◽

Renata Duchnowska ◽

Tomasz Trojanowski ◽

Tomasz Mandat ◽

Anna Kowalczyk ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Breast Tumors ◽

Steroid Receptor ◽

Receptor Expression ◽

Nuclear Staining ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Primary Tumors

603 Background: Breast cancer patients with HER2-positive tumors are at high risk for brain metastases. In the current study we examined expression of ER, PR and HER2 in primary breast tumors and in matched brain metastases, as changes of their levels might reflect modes of escape from therapy. Methods: Fifty-three pairs of matched formalin-fixed paraffin-embedded samples from primary breast cancers and brain metastases were assayed for ER and PR status by immuno-histochemistry, whereas HER2 expression was quantified using the novel HERmark assay. Nuclear staining of ER and PR >10%, and relative fluorescence of HER2 >17.8/mm2 were considered as positive results. Results: HER2 levels in brain metastases were generally higher than in the primary tumors (p = 3e-6), with a median increase of 1.9-fold (range 0.08 to 199-fold). There were also substantial differences in ER and PR status between primary tumors and brain metastases. Loss of steroid receptor positivity in brain metastases was more frequent than its gain (ER: 46% vs. 26%; p = 0.16; PR: 57% vs. 23%; p = 0.044). These changes resulted in a net increase in the number of HER2-positive/ER-negative brain metastases, which more than doubled the proportion of primary breast tumors with this phenotype (26% vs. 11%, respectively; p = 0.08). Additionally, HER2 levels in the primary tumors significantly correlated with overall survival when stratified by ER status (p = 0.011). Conclusions: Brain metastases of breast cancer show significant changes in steroid receptor status and in quantitative HER2 levels compared to matched primary tumors. These data provide a rationale for future studies and may help in designing treatment strategies that target the most likely escape pathways of breast cancer.

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JARID1A and IGF2R are concomitantly up-regulated in trastuzumab-treated human breast cancers.

10.31219/osf.io/734ux ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Growth Factor ◽

Expression Profiles ◽

Regulation Of Gene Expression ◽

Metastatic Breast ◽

Growth Factor Signaling ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Primary Tumors

Epigenetic regulation of gene expression is a mechanism by which signals transduced at the plasma membrane be can translated into differences in mRNA quantity and gene product at the protein level (1, 2). Trastuzumab is widely utilized for the treatment of adjuvant and metastatic breast cancer (3). We found, using analysis of public microarray and published multiplexed gene expression data (4, 5), that the histone lysine H3K4 demethylase JARID1A was among the genes whose expression was most significantly different when comparing the global gene expression profiles of trastuzumab-treated breast cancers and breast cancers not treated with trastuzumab. Expression of JARID1A in cancer cells has been associated with a drug-tolerant state with reduced drug sensitivity, dependent on insulin-like growth factor (IGF) signaling (6). Interestingly, we found that IGF2R was also among the genes whose expression was most significantly different transcriptome-wide when comparing the primary tumors of breast cancer patients treated with trastuzumab or not. These data clearly demonstrate up-regulation of a receptor for key growth factor signaling and together suggest that trastuzumab could be hard-wiring tumor cells for drug resistance.

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Prognostic Role of Hedgehog-GLI1 Signaling Pathway in Aggressive and Metastatic Breast Cancers

Current Drug Metabolism ◽

10.2174/1389200221666200122120625 ◽

2020 ◽

Vol 21 (1) ◽

pp. 33-43 ◽

Cited By ~ 1

Author(s):

Prasuja Rokkam ◽

Shailender Gugalavath ◽

Deepak Kakara Gift Kumar ◽

Rahul Kumar Vempati ◽

Rama Rao Malla

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Neural Development ◽

Splice Variants ◽

Metastatic Breast ◽

Basic Function ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Aberrant Expression ◽

Cellular Processes

Glioma-associated oncogene homolog 1 (GLI1) is reported as an amplified gene in human glioblastoma cells. It is a krupple like transcription factor, belonging to the zinc finger family. The basic function of GLI1 is normal neural development at various stages of human. The GLI1 gene was first mapped on the chromosome sub-bands 12q13.3-14.1. Further, single nucleotide polymorphism is mostly observed in translating a region of 5’ and 3’- UTR of GLI1 gene in addition to two post-transcriptional splice variants, GLIΔN and tGLI. Additionally, it also regulates a plethora of gene which mediates crucial cellular processes like proliferation, differentiation, oncogenesis, EMT, and metastasis. It also regulates tumor tolerance, chemoresistance, and radioresistance. Aberrant expression of GLI1 predicts the poor survival of breast cancer patients. GLI1 is an essential mediator of the SHH signaling pathway regulating self-renewal of stem cells, angiogenesis, and expression of FOXS1, CYR61. GLI1 mediated HH pathway can induce apoptosis. Hence, GLI1 can be a future diagnostic, prognostic marker, and as well as a potent target of therapeutics in breast cancer.

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MCM3 upregulation confers endocrine resistance in breast cancer and is a predictive marker of diminished tamoxifen benefit

npj Breast Cancer ◽

10.1038/s41523-020-00210-8 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Sanne Løkkegaard ◽

Daniel Elias ◽

Carla L. Alves ◽

Martin V. Bennetzen ◽

Anne-Vibeke Lænkholm ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cancer Patients ◽

Endocrine Therapy ◽

Endocrine Resistance ◽

Predictive Marker ◽

Endocrine Treatment ◽

Breast Cancer Patients ◽

Minichromosome Maintenance ◽

Primary Tumors

AbstractResistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer is a major clinical problem with poorly understood mechanisms. There is an unmet need for prognostic and predictive biomarkers to allow appropriate therapeutic targeting. We evaluated the mechanism by which minichromosome maintenance protein 3 (MCM3) influences endocrine resistance and its predictive/prognostic potential in ER+ breast cancer. We discovered that ER+ breast cancer cells survive tamoxifen and letrozole treatments through upregulation of minichromosome maintenance proteins (MCMs), including MCM3, which are key molecules in the cell cycle and DNA replication. Lowering MCM3 expression in endocrine-resistant cells restored drug sensitivity and altered phosphorylation of cell cycle regulators, including p53(Ser315,33), CHK1(Ser317), and cdc25b(Ser323), suggesting that the interaction of MCM3 with cell cycle proteins is an important mechanism of overcoming replicative stress and anti-proliferative effects of endocrine treatments. Interestingly, the MCM3 levels did not affect the efficacy of growth inhibitory by CDK4/6 inhibitors. Evaluation of MCM3 levels in primary tumors from four independent cohorts of breast cancer patients receiving adjuvant tamoxifen mono-therapy or no adjuvant treatment, including the Stockholm tamoxifen (STO-3) trial, showed MCM3 to be an independent prognostic marker adding information beyond Ki67. In addition, MCM3 was shown to be a predictive marker of response to endocrine treatment. Our study reveals a coordinated signaling network centered around MCM3 that limits response to endocrine therapy in ER+ breast cancer and identifies MCM3 as a clinically useful prognostic and predictive biomarker that allows personalized treatment of ER+ breast cancer patients.

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Iodine Map Radiomics in Breast Cancer: Prediction of Metastatic Status

Cancers ◽

10.3390/cancers13102431 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2431

Author(s):

Lukas Lenga ◽

Simon Bernatz ◽

Simon S. Martin ◽

Christian Booz ◽

Christine Solbach ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast ◽

Principal Component ◽

Validation Dataset ◽

Dual Energy Ct ◽

Cancer Tissue ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Iodine Map ◽

Iodine Maps

Dual-energy CT (DECT) iodine maps enable quantification of iodine concentrations as a marker for tissue vascularization. We investigated whether iodine map radiomic features derived from staging DECT enable prediction of breast cancer metastatic status, and whether textural differences exist between primary breast cancers and metastases. Seventy-seven treatment-naïve patients with biopsy-proven breast cancers were included retrospectively (41 non-metastatic, 36 metastatic). Radiomic features including first-, second-, and higher-order metrics as well as shape descriptors were extracted from volumes of interest on iodine maps. Following principal component analysis, a multilayer perceptron artificial neural network (MLP-NN) was used for classification (70% of cases for training, 30% validation). Histopathology served as reference standard. MLP-NN predicted metastatic status with AUCs of up to 0.94, and accuracies of up to 92.6 in the training and 82.6 in the validation datasets. The separation of primary tumor and metastatic tissue yielded AUCs of up to 0.87, with accuracies of up to 82.8 in the training, and 85.7 in the validation dataset. DECT iodine map-based radiomic signatures may therefore predict metastatic status in breast cancer patients. In addition, microstructural differences between primary and metastatic breast cancer tissue may be reflected by differences in DECT radiomic features.

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The molecular landscape of Asian breast cancers reveals clinically relevant population-specific differences

Nature Communications ◽

10.1038/s41467-020-20173-5 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Jia-Wern Pan ◽

Muhammad Mamduh Ahmad Zabidi ◽

Pei-Sze Ng ◽

Mei-Yee Meng ◽

Siti Norhidayu Hasan ◽

...

Keyword(s):

Breast Cancer ◽

Somatic Mutations ◽

Checkpoint Inhibitors ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Breast Tumours ◽

Different Populations ◽

Caucasian Women ◽

Molecular Landscape ◽

Immune Score

AbstractMolecular profiling of breast cancer has enabled the development of more robust molecular prognostic signatures and therapeutic options for breast cancer patients. However, non-Caucasian populations remain understudied. Here, we present the mutational, transcriptional, and copy number profiles of 560 Malaysian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to breast tumours in Caucasian women, we show an increased prevalence of HER2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. We also observe elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst HER2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations.

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