scholarly journals Ca2+ Signaling as the Untact Mode during Signaling in Metastatic Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1473
Author(s):  
Dongun Lee ◽  
Jeong Hee Hong
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Metastasis ◽  
Therapeutic Potential ◽  
Tumor Development ◽  
Treatment Strategies ◽  
Metastatic Breast ◽  
Breast Cancer Metastasis ◽  
The Brain ◽  
Ca2 Channels

Metastatic features of breast cancer in the brain are considered a common pathology in female patients with late-stage breast cancer. Ca2+ signaling and the overexpression pattern of Ca2+ channels have been regarded as oncogenic markers of breast cancer. In other words, breast tumor development can be mediated by inhibiting Ca2+ channels. Although the therapeutic potential of inhibiting Ca2+ channels against breast cancer has been demonstrated, the relationship between breast cancer metastasis and Ca2+ channels is not yet understood. Thus, we focused on the metastatic features of breast cancer and summarized the basic mechanisms of Ca2+-related proteins and channels during the stages of metastatic breast cancer by evaluating Ca2+ signaling. In particular, we highlighted the metastasis of breast tumors to the brain. Thus, modulating Ca2+ channels with Ca2+ channel inhibitors and combined applications will advance treatment strategies for breast cancer metastasis to the brain.

scholarly journals Hotspot ESR1 mutations are multimodal and contextual drivers of breast cancer metastasis

2021 ◽  
Author(s):  
Zheqi Li ◽  
Yang Wu ◽  
Megan E. Yates ◽  
Nilgun Tasdemir ◽  
Amir Bahreini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Metastasis ◽  
De Novo ◽  
Endocrine Resistance ◽  
Treatment Strategies ◽  
Metastatic Breast ◽  
Estrogen Receptor Α ◽  
Breast Cancer Metastasis ◽  
Cell Models

AbstractConstitutively active estrogen receptor-α (ER/ESR1) mutations have been identified in approximately one third of ER+ metastatic breast cancer. Although these mutations are known mediators of endocrine resistance, their potential role in promoting metastatic disease has not yet been mechanistically addressed. In this study, we show the presence of ESR1 mutations exclusively in distant, but not local recurrences. In concordance with transcriptomic profiling of ESR1 mutant tumors, genome-edited Y537S and D538G cell models have a reprogrammed cell adhesive gene network via alterations in desmosome/gap junction genes and the TIMP3/MMP axis, which functionally confers enhanced cell-cell contacts while decreased cell-ECM adhesion. Context-dependent migratory phenotypes revealed co-targeting of Wnt and ER as vulnerability. Mutant ESR1 exhibits non-canonical regulation of several metastatic pathways including secondary transactivation and de novo FOXA1-driven chromatin remodeling. Collectively, our data supports evidence for ESR1 mutation-driven metastases and provides insight for future preclinical therapeutic strategies.SignificanceContext and allele-dependent transcriptome and cistrome reprogramming in genome-edited ESR1 mutation cell models elicit diverse metastatic phenotypes, including but not limited to alterations in cell adhesion and migration. The gain-of-function mutations can be pharmacologically targeted, and thus may be key components of novel therapeutic treatment strategies for ER-mutant metastatic breast cancer.

scholarly journals Exosomal MicroRNAs and Organotropism in Breast Cancer Metastasis

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1827 ◽  
Author(s):  
Grace L. Wong ◽  
Sara Abu Jalboush ◽  
Hui-Wen Lo
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Metastasis ◽  
Current Knowledge ◽  
Metastatic Breast ◽  
Tumor Stroma ◽  
Breast Cancer Metastasis ◽  
Exosomal Mirnas ◽  
Made In

Breast cancer is the most frequent malignancy for women in which one in eight women will be diagnosed with the disease in their lifetime. Despite advances made in treating primary breast cancer, there is still no effective treatment for metastatic breast cancer. Consequently, metastatic breast cancer is responsible for 90% of breast cancer-related deaths while only accounting for approximately one third of all breast cancer cases. To help develop effective treatments for metastatic breast cancer, it is important to gain a deeper understanding of the mechanisms by which breast cancer metastasizes, particularly, those underlying organotropism towards brain, bone, and lungs. In this review, we will primarily focus on the roles that circulating exosomal microRNAs (miRNAs) play in organotropism of breast cancer metastasis. Exosomes are extracellular vesicles that play critical roles in intercellular communication. MicroRNAs can be encapsulated in exosomes; cargo-loaded exosomes can be secreted by tumor cells into the tumor microenvironment to facilitate tumor–stroma interactions or released to circulation to prime distant organs for subsequent metastasis. Here, we will summarize our current knowledge on the biogenesis of exosomes and miRNAs, mechanisms of cargo sorting into exosomes, the exosomal miRNAs implicated in breast cancer metastasis, and therapeutic exosomal miRNAs.

Factors associated with mortality after breast cancer metastasis.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 174-174
Author(s):  
S. Y. Jung ◽  
M. Q. Rosenzweig ◽  
S. M. Sereika ◽  
F. Linkov ◽  
A. Brufsky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Cancer Metastasis ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Breast Cancer Metastasis ◽  
Her2 Status ◽  
Breast Cancer Patients

174 Background: It is generally accepted that patients with breast cancer metastases have poor survival. Metastatic breast cancer patients can be considered a heterogeneous population with a varied clinical course, which underscores the need for accurate prediction of survival based on prognostic factors. The purpose of the present study was to identify factors related to survival in breast cancer patients after diagnosis with metastatic disease. Methods: A total of 557 patients with breast cancer metastasis diagnosis seen at one large urban practice have been followed up between January 1, 1999 and June 30, 2008. Demographic, tumor characteristics, clinical factors as predictors of survival were analyzed using Cox regression model. Results: The median survival length was 40 months (range 1-114 months) with 269 (48.3%) alive and 288 (51.7%) dead. This study demonstrated that hypertension, estrogen receptor (ER) and/or progesterone receptor (PR) status, human epidermal growth factor receptor-2 (HER2) status, number of metastatic sites, and body mass index (BMI) at diagnosis with metastatic breast cancer were the most relevant prognostic factors for survival after metastasis. Conclusions: Findings of this study may form a foundation for the corpus of knowledge explaining the outcome differences in treatment of patients with metastatic breast cancer, potentially helping to create tailored counseling and personalized treatment approaches for this vulnerable group. [Table: see text]

Metastatic Breast Cancer, Organotropism and Therapeutics: A Review

2021 ◽  
Vol 21 ◽  
Author(s):  
Ajaz Ahmad Waza ◽  
Najeebul Tarfeen ◽  
Sabhiya Majid ◽  
Yasmeena Hassan ◽  
Rashid Mir ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Metastatic Breast ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Metastases ◽  
Cancer Metastases ◽  
Main Culprit

: The final stage of breast cancer involves spreading breast cancer cells to the vital organs like the brain, liver lungs and bones in the process called metastasis. Once the target organ is overtaken by the metastatic breast cancer cells, its usual function is compromised causing organ dysfunction and death. Despite the significant research on breast cancer metastasis, it’s still the main culprit of breast cancer-related deaths. Exploring the complex molecular pathways associated with the initiation and progression of breast cancer metastasis could lead to the discovery of more effective ways of treating the devastating phenomenon. The present review article highlights the recent advances to understand the complexity associated with breast cancer metastases, organotropism and therapeutic advances.

scholarly journals ARID1A Mutation in Metastatic Breast Cancer: A Potential Therapeutic Target

2021 ◽  
Vol 11 ◽  
Author(s):  
Xuan Cheng ◽  
Jian-Xiong Zhao ◽  
Feng Dong ◽  
Xu-Chen Cao
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Therapeutic Potential ◽  
Endocrine Resistance ◽  
Hdac Inhibitors ◽  
Treatment Strategies ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Luminal A

Distant metastasis is the principal cause of mortality for breast cancer patients. Targeting specific mutations that have been acquired during the evolution process of advanced breast cancer is a potential means of enhancing the clinical efficacy of treatment strategies. In metastatic breast cancer, ARID1A is the most prevalent mutation of the SWI/SNF complex, which regulates DNA repair, recombination, and gene transcription. The low expression of ARID1A is associated with poor disease-free survival and overall survival of patients with luminal A or HER2-rich breast cancer. In addition, ARID1A plays a prominent role in maintaining luminal characteristics and has an advantage for identifying responses to treatment, including endocrine therapies, HDAC inhibitors and CDK4/6 inhibitors. The therapeutic vulnerabilities initiated by ARID1A alterations encourage us to explore new approaches to cope with ARID1A mutant-related drug resistance or metastasis. In this review, we describe the mutation profiles of ARID1A in metastatic breast cancer and the structure and function of ARID1A and the SWI/SNF complex as well as discuss the potential mechanisms of ARID1A-mediated endocrine resistance and therapeutic potential.

scholarly journals HUNK phosphorylates EGFR to regulate breast cancer metastasis

Oncogene ◽  
2019 ◽  
Vol 39 (5) ◽  
pp. 1112-1124 ◽  
Author(s):  
Carly B. Williams ◽  
Kendall Phelps-Polirer ◽  
Ivan P. Dingle ◽  
Christina J. Williams ◽  
Matthew J. Rhett ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Metastasis ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Breast Cancer Metastasis ◽  
Migration And Invasion ◽  
Breast Cancers ◽  
Kinase Substrate ◽  
Downstream Signaling

Abstract Epidermal growth factor receptor (EGFR) is commonly over-expressed in metastatic breast cancer yet metastatic breast cancer is generally resistant to anti-EGFR therapies, and the mechanism for resistance to EGFR inhibitors in this setting is not fully understood. Hormonally up-regulated neu-associated kinase (HUNK) kinase is up-regulated in aggressive breast cancers and is thought to play a role in breast cancer metastasis. However, no studies have been conducted to examine a relationship between EGFR and HUNK in breast cancer metastasis. We performed a kinase substrate screen and identified that EGFR is phosphorylated by HUNK. Our studies show that HUNK phosphorylates EGFR at T654, enhancing receptor stability and downstream signaling. We found that increased phosphorylation of T654 EGFR correlates with increased epithelial to mesenchymal, migration and invasion, and metastasis. In addition, we found that HUNK expression correlates with overall survival and distant metastasis free survival. This study shows that HUNK directly phosphorylates EGFR at T654 to promote metastasis and is the first study to show that the phosphorylation of this site in EGFR regulates metastasis.

Metastatic breast cancer in regrowth of thyroid lobe after subtotal thyroidectomy – case report

2019 ◽  
Vol 92 (5) ◽  
pp. 1-3
Author(s):  
Joanna Pakuła ◽  
Tomasz Stępień ◽  
Krzysztof Kuzdak
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Metastasis ◽  
Malignant Neoplasm ◽  
Metastatic Breast ◽  
Breast Cancer Metastasis ◽  
Thyroid Lobe ◽  
Total Recovery ◽  
Oncological Treatment ◽  
The Right

Breast cancer is the most common malignant neoplasm among women. Metastases to the thyroid are relatively rare. Those lesions annunciate neoplasm dissemination in most cases. Metastatic breast cancer of thyroid lobe regrowth hasn’t been described yet. In the article the authors present a case of a 66-year old women with isolated, metachronous breast cancer metastasis in regrowth of the right thyroid lobe. Resection of the right lobe with metastatic tumor was performed with a purpose of total recovery. Despite surgery, multiple bone metastases were detected a few months after. In conclusion, regrowth of the thyroid is a potential site of recurrence and metastasis. Therefore, the thyroid bed cannot be omitted in routine examination during and after oncological treatment.

scholarly journals Metastasis: A Bane of Breast Cancer Therapy

2020 ◽  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Tumour Size ◽  
Metastatic Breast ◽  
Metastatic Potential ◽  
Breast Cancer Metastasis ◽  
Mesenchymal Transition

The underlying mechanisms of metastasis in patients with breast cancer is still poorly understood. Approximately 6% of patients with breast cancer present with metastasis at the time of diagnosis. Metastatic breast cancer is difficult to treat and patients with breast cancer with distant metastasis have a significantly lower 5-year survival rate compared to patients with localised breast cancer (27% and 99%, respectively). During breast cancer progression, tumour cells first metastasise to nearby draining lymph nodes and then to distant organs, primarily bone, lungs, liver, and brain. In this brief review, the authors discuss breast cancer metastasis, the role of epithelial–mesenchymal transition and the contributions of the immune system to the metastatic process. The authors also briefly discuss whether there is any relationship between tumour size and metastatic potential, and recent advances in treatment for metastatic breast cancer. The studies highlighted suggest that immunotherapy may play a more significant role in future patient care for metastatic breast cancer.

Rab11 family-interacting protein 4, RAB11FIP4, is a differentially expressed gene in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Interacting Protein ◽  
Primary Tumors ◽  
Free Survival ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that Rab11 family-interacting protein 4, encoded by RAB11FIP4, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. RAB11FIP4 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of RAB11FIP4 in primary tumors was significantly correlated with patient recurrence-free survival and distant metastasis-free survival. Modulation of RAB11FIP4 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

scholarly journals Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B)

Breast Cancer ◽  
2021 ◽  
Author(s):  
Takamichi Yokoe ◽  
Sasagu Kurozumi ◽  
Kazuki Nozawa ◽  
Yukinori Ozaki ◽  
Tetsuyo Maeda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Real World ◽  
Treatment Strategies ◽  
Metastatic Breast ◽  
Trastuzumab Emtansine ◽  
Breast Cancer Patients ◽  
Her2 Positive

Abstract Background Trastuzumab emtansine (T-DM1) treatment for human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer after taxane with trastuzumab and pertuzumab is standard therapy. However, treatment strategies beyond T-DM1 are still in development with insufficient evidence of their effectiveness. Here, we aimed to evaluate real-world treatment choice and efficacy of treatments after T-DM1 for HER2-positive metastatic breast cancer. Methods In this multi-centre retrospective cohort study involving 17 hospitals, 325 female HER2-positive metastatic breast cancer patients whose post-T-DM1 treatment began between April 15, 2014 and December 31, 2018 were enrolled. The primary end point was the objective response rate (ORR) of post-T-DM1 treatments. Secondary end points included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS). Results The median number of prior treatments of post-T-DM1 treatment was four. The types of post-T-DM1 treatments included (1) chemotherapy in combination with trastuzumab and pertuzumab (n = 102; 31.4%), (2) chemotherapy concomitant with trastuzumab (n = 78; 24.0%), (3), lapatinib with capecitabine (n = 63; 19.4%), and (4) others (n = 82; 25.2%). ORR was 22.8% [95% confidence interval (CI): 18.1–28.0], DCR = 66.6% (95% CI 60.8–72.0), median PFS = 6.1 months (95% CI 5.3–6.7), median TTF = 5.1 months (95% CI 4.4–5.6), and median OS = 23.7 months (95% CI 20.7–27.4). Conclusion The benefits of treatments after T-DM1 are limited. Further investigation of new treatment strategies beyond T-DM1 is awaited for HER2-positive metastatic breast cancer patients.

Sign in / Sign up

Export Citation Format

Share Document