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

2020 ◽  
Vol 21 (1) ◽  
pp. 33-43 ◽  
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.

scholarly journals Iodine Map Radiomics in Breast Cancer: Prediction of Metastatic Status

Cancers ◽  
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.

scholarly journals The PI3K Pathway: Background and Treatment Approaches

Breast Care ◽  
2016 ◽  
Vol 11 (6) ◽  
pp. 398-404 ◽  
Author(s):  
Michael P. Lux ◽  
Peter A. Fasching ◽  
Michael G. Schrauder ◽  
Alexander Hein ◽  
Sebastian M. Jud ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Tamoxifen Treatment ◽  
Breast Cancer Patients ◽  
Secondary Resistance ◽  
Treatment Approaches ◽  
Metastatic Breast Carcinoma ◽  
Promising Therapeutic Approach

Two-thirds of all breast cancer patients with metastases have a hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative subtype. Endocrine therapy is the treatment of choice in these patients since in addition to its effectiveness it can also maintain the patients' quality of life over a longer term. However, 44-62% of postmenopausal patients with metastatic breast carcinoma have primary tamoxifen resistance. After 3-5 years, 30-40% of the patients receiving tamoxifen treatment develop secondary resistance. Understanding the way in which resistance develops is therefore essential for developing treatment approaches that can prevent or reverse endocrine resistance. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role here. As a result of the numerous interactions involved, complex issues arise that need to be taken into account in the development and use of therapeutic agents. In addition, this signaling pathway is the one that most frequently undergoes mutations in breast cancer. The prognostic and predictive significance of individual mutations has not yet been fully explained, but it might provide a basis for patient selection in clinical studies. Initial research results on the use of PI3K inhibitors suggest that this may be a highly promising therapeutic approach, with an acceptable side effect profile.

Suppressions of metastatic breast cancer invasion and metastasis to brain/cross talk HER2/ERK1/2/MMP-9 signaling pathway

2018 ◽  
Vol 6 (4) ◽  
pp. 349-361
Author(s):  
Yu-Chun Lin ◽  
Dong-Qing Chin
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Signaling Pathway ◽  
Metastatic Breast ◽  
Cancer Invasion ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Invasion And Metastasis ◽  
Matrigel Invasion ◽  
Breast Cancer Invasion

Understanding the molecular pathways that contribute to the development of metastatic breast cancer invasion and metastasis to brain is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER2/ERK1/2/MMP-9 signaling pathway in breast cancer. We performed Global exon array to study the expression of ERK1/2/MMP-9 signaling pathway in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of ERK1/2/MMP-9 proteins in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells.

Metastatic male breast cancer (mMBC): Prognosis and survival of 35 patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e12001-e12001
Author(s):  
R. Foerster ◽  
F. G. Foerster ◽  
D. Baaske ◽  
B. Schubotz ◽  
V. Wulff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Male Breast Cancer ◽  
Systemic Therapy ◽  
Metastatic Breast ◽  
Male Breast ◽  
Tumor Characteristics ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Radio Therapy

e12001 Background: Only about 1% of breast cancers occur in men, respectively 400–500 new cases per year in Germany. Clinical studies on breast cancer in men are limited for case studies or retrospective analysis. In the recent years no studies have been published on the clinical course of mMBC. Therefore we here present a retrospective cohort study on this topic. Methods: Clinical and pathological tumor characteristics and the follow-up of male breast cancer patients with metastatic disease diagnosed in the region Chemnitz/Zwickau in the state of Saxony between 1995 and 2007 were documented and statistically evaluated. Results: 35 men (median age 64.7 years) were diagnosed with mMBC; 10 (28.6%) of them with primary metastasis. Median survival time: 37 months. 85.7% (n = 30) had an invasive-ductile carcinoma. Most common localizations of metastasis: bones (n = 19), lungs (n = 19), liver (n = 7). Tumor characteristics at the point of diagnosis: 63.9% (n = 22) T2-T4, 38.7% (n = 12) G3, 48.4% (n = 15) N+, 79.3% (n = 23) ER+, 72.4% (n = 21) PgR+, 12.5% (n = 3) HER-2+, 13.8% (n = 4) triple negatives, and 69.2% (n = 9) AR+. The therapy in the metastatic state was very heterogeneous and consisted of systemic endocrine therapy in 45.5% (n = 10), systemic chemo therapy in 9% (n = 2) or a combination of both in 45.5% (n = 10). In 14 (40%) cases a palliative radio therapy was administered. The initial tumor characteristics like tumor size, nodal state and grading were not of any prognostic relevance on a future development of metastasis. Prognostic unfortunate were a negative hormone receptor state (p < 0.001) and triple negative receptor state (n.s.). Patients with primary metastasis showed a tendency towards worse survival than patients who developed the metastasis during follow up (n.s.). If a systemic therapy was given the prognosis was significantly improved (p < 0.005). Conclusions: Patients suffering from metastatic male breast cancer had a comparatively good prognosis and showed significant benefit from systemic therapy in this study. In patients with negative receptor state and without systemic therapy the prognosis was especially worsened. Our data suggest that an up-to-date adequate systemic therapy is capable of improving survival in men with metastatic breast cancer. No significant financial relationships to disclose.

scholarly journals Estrogen receptor mutations and splice variants determined in liquid biopsies from metastatic breast cancer patients

2017 ◽  
Vol 12 (1) ◽  
pp. 48-57 ◽  
Author(s):  
Nick Beije ◽  
Anieta M. Sieuwerts ◽  
Jaco Kraan ◽  
Ngoc M. Van ◽  
Wendy Onstenk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Splice Variants ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Liquid Biopsies

scholarly journals Real-World Data on Apatinib Efficacy - Results of a Retrospective Study in Metastatic Breast Cancer Patients Pretreated With Multiline Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhaoyun Liu ◽  
Jing Shan ◽  
Qian Yu ◽  
Xinzhao Wang ◽  
Xiang Song ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Real World ◽  
Metastatic Breast ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Real World Data ◽  
Significant Treatment ◽  
Nccn Guidelines

ObjectivesThe NCCN guidelines recommend that the addition of bevacizumab should be considered in metastatic breast cancers in some circumstances, but there are no recommendations for the similar antiangiogenic drug apatinib. The aim of this study was to evaluate the safety and efficacy of apatinib in metastatic breast cancer patients pretreated with multiline treatment in a real-world setting.Materials and MethodsMetastatic breast cancer patients pretreated with multiline treatment who had apatinib treatment initiated from September 2015 to August 2019 at Shandong Cancer Hospital and Institute were included. The primary endpoints included PFS and OS, and the secondary endpoint was treatment-related toxicity.ResultsA total of 66 patients with metastatic breast cancer received apatinib treatment after failure of multiline chemotherapy in this study. The median PFS and OS of all 66 patients were 6.0 months and 10.0 months, respectively. The clinical beneficial rate was 40.9%. All patients tolerated treatment well, and no patients died of toxicity. The common toxicities of apatinib were hand and foot syndrome, secondary hypertension and fatigue events. The number of prior chemotherapy regimens was significantly associated with DFS and OS. Capecitabine may be a better choice for combination with a longer median OS of 19 months, while apatinib combined with other drugs was 9 months, and the apatinib monotherapy was 10 months.ConclusionApatinib produced moderate efficacy in metastatic breast cancer patients pretreated with multiline treatment with no significant treatment-related adverse events. Apatinib might be a choice for women as a maintenance salvage therapy following multiline chemotherapy failure.

Effects of improved hypoallergenic fabrics in medical wigs in patients with breast cancer with chemotherapy-induced alopecia: a randomised clinical trial

2021 ◽  
pp. bmjspcare-2020-002309
Author(s):  
Nao Tamai ◽  
Takeo Minematsu ◽  
Mari Ikeda ◽  
Yuko Mugita ◽  
Hiromi Sanada
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Intervention Group ◽  
Metastatic Breast ◽  
Randomised Clinical Trial ◽  
Controlled Study ◽  
Control Group ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Barrier Functions

PurposeChemotherapy causes changes in appearance in patients with cancer. Therefore, to have a normal life, it is necessary for patients to wear a wig. However, wearing a wig may strain an already sensitive scalp during chemotherapy. This study aimed to assess the effects of a hypoallergenic medical wig in breast cancer patients with chemotherapy-induced alopecia (CIA).MethodsA randomised, single-blind, controlled study was conducted from January 2015 to July 2017 in Tokyo, Japan. Women with non-metastatic breast cancers were enrolled. Participants were provided a hypoallergenic medical wig or a traditional medical wig. The primary endpoint was incidence of scalp dermatitis, including erythema, rash and erosion. The secondary endpoints were incidence of scalp symptoms, alterations in scalp barrier functions and quality of life (QOL). Patients were followed at the start of the first chemotherapy administration and at 13th week.ResultsFifty-nine women were included in the analysis. At 13th week, the incidence of erythema was 44.8% among patients in the intervention group and 86.7% among patients in the control group, in the intention-to-treat analysis (p<0.01). The incidence of erosion tended to decrease in the intervention group at the 13th week (p=0.09). The incidence of scalp symptoms, alterations in scalp barrier functions and QOL were not significantly different between the groups.ConclusionsThe incidence of dermatitis, including erythema, rash and erosion, decreased when wearing the new hypoallergenic medical wig. The gentle hypoallergenic medical wig is useful in improving erythema in cancer patients with CIA.Trial registration number UMIN000021289.

Suppressions of metastatic breast cancer invasion and metastasis to brain/cross talk HER2/ERK1/2/MMP-9 signaling pathway

2016 ◽  
Vol 4 (2) ◽  
pp. 227-239
Author(s):  
Yu-Chun Lin ◽  
Dong-Qing Chin
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Signaling Pathway ◽  
Metastatic Breast ◽  
Cancer Invasion ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Invasion And Metastasis ◽  
Matrigel Invasion ◽  
Breast Cancer Invasion

Understanding the molecular pathways that contribute to the development of metastatic breast cancer invasion and metastasis to brain is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER2/ERK1/2/MMP-9 signaling pathway in breast cancer. We performed Global exon array to study the expression of ERK1/2/MMP-9 signaling pathway in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of ERK1/2/MMP-9 proteins in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells.

Neuregulin Expression Modulates Clinical Response to Trastuzumab in Patients With Metastatic Breast Cancer

2007 ◽  
Vol 25 (19) ◽  
pp. 2656-2663 ◽  
Author(s):  
Enrique de Alava ◽  
Alberto Ocaña ◽  
Mar Abad ◽  
Juan Carlos Montero ◽  
Azucena Esparís-Ogando ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Early Stage ◽  
Metastatic Breast ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Event Free Survival ◽  
Mcf7 Cells ◽  
Free Survival ◽  
Her 2

Purpose Human epidermal growth factor receptor 2 (HER-2) overexpression has been associated with the genesis and progression of a subset of breast cancers. The function of HER-2 may be upregulated by overexpression or by the availability of neuregulins (NRGs), a group of transmembrane growth factors. Transmembrane NRGs strongly activated HER-2 and cell proliferation in breast cancer cells that did not overexpress HER-2, and treatment with trastuzumab prevented the proliferative action of transmembrane NRG. This raised the relevant clinical question of whether patients considered as HER-2 negative, but expressing transmembrane NRG, may benefit from treatment with trastuzumab. Patients and Methods MCF7 cells expressing transmembrane NRG (MCF7-NRGα2c) were injected into mice, and their sensitivity to trastuzumab was assessed. A retrospective study of 124 patients with early-stage or metastatic breast cancer was conducted. Expression of transmembrane NRG was evaluated by immunohistochemistry. In 11 patients, Western blot for NRGs was also carried out. Statistics were performed to analyze possible correlations between NRG expression and response to trastuzumab-based therapies, event-free survival, and overall survival (OS). Results Trastuzumab inhibited tumor growth in mice injected with MCF7-NRGα2c cells. Transmembrane NRG was frequently expressed in breast cancer patients. Overexpression of transmembrane NRG significantly correlated with a longer event-free survival and OS in patients with low or normal HER-2 expression who were treated with trastuzumab-based therapies but not in patients with HER-2 overexpression. Conclusion We suggest that the spectrum of patients who may benefit from trastuzumab-based therapies may be widened to include patients with metastatic breast cancer without HER-2 amplification but who express transmembrane NRGs.

scholarly journals Frequency locally advanced and metastatic breast cancer at the time of presentation in a private hospital in Peshawar.

2019 ◽  
Vol 26 (10) ◽  
pp. 1693-1696
Author(s):  
Amjad Ali
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Disease ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Late Presentation ◽  
Hard Copy ◽  
Medical Institute ◽  
Breast Cancers ◽  
Breast Cancer Patients

Breast cancer is the most common cancer among women and Pakistan has the highest rate of breast cancers in Asia. Breast cancer patients present very late with their symptoms in Pakistan as compared to the developed world. As a result, our survival outcomes are very poor. To estimate the frequency of breast cancer patients presenting with locally advanced and metastatic disease at presentation at our dedicated one-stop breast care unit (BCU) at Rehman Medical Institute Peshawar. Study Design: Observational study. Setting: Rehman Medical Institute Peshawar. Period: 1st January 2018 to 31st December 2018. Material and Methods: Data was prospectively collected of all breast cancer patients presenting to BCU and recorded both electronically and in hard copy, and analysed. Results: A total of 83 patients were identified. 30% of the patients had metastatic disease at presentation while 34% had locally advanced disease. Only 36% had early breast cancer. Conclusion: This study supported the previously reported trend of very late presentation of patients with breast cancer in Pakistan.

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