scholarly journals Breast Cancer with Bone Metastasis: Molecular Insights and Clinical Management

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1377
Author(s):  
Konstantinos Venetis ◽  
Roberto Piciotti ◽  
Elham Sajjadi ◽  
Marco Invernizzi ◽  
Stefania Morganti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Clinical Management ◽  
Bone Destruction ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Incurable Condition ◽  
Skeletal Related Events ◽  
Relevant Topic ◽  
Systemic Therapies

Despite the remarkable advances in the diagnosis and treatment of breast cancer patients, the presence or development of metastasis remains an incurable condition. Bone is one of the most frequent sites of distant dissemination and negatively impacts on patient’s survival and overall frailty. The interplay between tumor cells and the bone microenvironment induces bone destruction and tumor progression. To date, the clinical management of bone metastatic breast cancer encompasses anti-tumor systemic therapies along with bone-targeting agents, aimed at slowing bone resorption to reduce the risk of skeletal-related events. However, their effect on patients’ survival remains controversial. Unraveling the biology that governs the interplay between breast neoplastic cells and bone tissue would provide means for the development of new therapeutic agents. This article outlines the state-of-the art in the characterization and targeting the bone metastasis in breast cancer, focusing on the major clinical and translational studies on this clinically relevant topic.

scholarly journals S100A4 released from highly bone-metastatic breast cancer cells plays a critical role in osteolysis

Bone Research ◽  
2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Haemin Kim ◽  
Bongjun Kim ◽  
Sang Il Kim ◽  
Hyung Joon Kim ◽  
Brian Y. Ryu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Bone Loss ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Critical Role ◽  
Bone Destruction ◽  
Metastatic Breast ◽  
Breast Cancer Patients

Abstract Bone destruction induced by breast cancer metastasis causes severe complications, including death, in breast cancer patients. Communication between cancer cells and skeletal cells in metastatic bone microenvironments is a principal element that drives tumor progression and osteolysis. Tumor-derived factors play fundamental roles in this form of communication. To identify soluble factors released from cancer cells in bone metastasis, we established a highly bone-metastatic subline of MDA-MB-231 breast cancer cells. This subline (mtMDA) showed a markedly elevated ability to secrete S100A4 protein, which directly stimulated osteoclast formation via surface receptor RAGE. Recombinant S100A4 stimulated osteoclastogenesis in vitro and bone loss in vivo. Conditioned medium from mtMDA cells in which S100A4 was knocked down had a reduced ability to stimulate osteoclasts. Furthermore, the S100A4 knockdown cells elicited less bone destruction in mice than the control knockdown cells. In addition, administration of an anti-S100A4 monoclonal antibody (mAb) that we developed attenuated the stimulation of osteoclastogenesis and bone loss by mtMDA in mice. Taken together, our results suggest that S100A4 released from breast cancer cells is an important player in the osteolysis caused by breast cancer bone metastasis.

scholarly journals Karakteristik Klinikopatologik Pasien Kanker Payudara dengan Metastasis Tulang di RSUP Sanglah pada Tahun 2014 - 2018

e-CliniC ◽  
2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Putu Krishna B. S. Putra ◽  
I Wayan J. Sumadi ◽  
Ni Putu Sriwidyani ◽  
IG Budhi Setiawan
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Patients ◽  
Invasive Carcinoma ◽  
Molecular Subtype ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Luminal B ◽  
Histopathological Type

Abstract: Breast cancer is the most common cancer in woman. Metastasis often occurs especially to the bones. This study was aimed to determine the characteristics of breast cancer patients with bone metastasis. This was a descriptive study with a cross-sectional design. Samples were 46 breast cancer patients with bone metastasis recorded at Sanglah Hospital from 2014 until 2018. Data of pathological examination archives of Oncology Surgery Division Medical Faculty of Udayana University/Sanglah General Hospital were used to obtain the clinicopathological characteristics of metastatic breast cancer patients based on age, lateralization, histopathological type, and tumor molecular subtype. The results showed that most cases of metastatic breast cancer were aged 40-49 years as many 21 patients (45.7%), minimal difference in lateralization between right breast as many 22 patients (47.8%) and left breast 23 patients (50%). The most common histopathological type was invasive carcinoma of no special type as many 34 patients (73.9%). The most common tumor subtype was the luminal B subtype as many 21 patients (45.7%). In conclusion, most patients of breast cancer with bone metastasis were 40-49 years old, invasive carcinoma of no special type, molecular subtype of luminal B, and no significant difference between lateralization to the right and left breast.Keywords: breast cancer, bone, metastasis, clinicopathological caharacteristics Abstrak: Kanker payudara merupakan jenis kanker yang paling sering dijumpai pada wanita. Metastasis sering terjadi terutama pada tulang. Penelitian ini bertujuan untuk mengetahui karakteristik pasien kanker payudara dengan metastasis tulang di RSUP Sanglah Denpasar. Jenis penelitian ialah deskriptif dengan desain potong lintang. Sampel penelitian ialah 46 pasien kanker payudara dengan metastasis tulang yang tercatat di RSUP Sanglah tahun 2014-2018. Data diambil dari arsip hasil pemeriksaan patologi di Subdivisi Bedah Onkologi, Departemen/Kelompok Staf Medis (KSM) Bedah Fakultas Kedokteran Universitas Udayana (FK UNUD)/RSUP Sanglah untuk mendapatkan karakteristik klinikopatologi pasien kanker payudara metastasis tulang berdasarkan usia, lateralisasi, tipe histopatologik, dan subtipe molekuler tumor. Hasil penelitian menunjukkan kasus terbanyak terjadi pada rentang usia 40-49 tahun sebanyak 21 orang (45,7%), dengan lateralisasi tidak jauh berbeda antara payudara kanan sebanyak 22 orang (47,8) dan kiri sebanyak 23 orang (50%). Tipe histopatologik yang lebih sering ditemukan yaitu invasive carcinoma of no special type sebanyak 34 orang (73,9%). Subtipe molekuler yang paling banyak ditemukan ialah subtipe luminal B sebanyak 21 orang (45,7%). Simpulan penelitian ini pasien kanker payudara dengan metastasis tulang berada pada rentang usia 40-49 tahun, invasive carcinoma of no special type, subtipe molekuler luminal B. dan lateralisasi payudara kanan dan kiri tidak jauh berbeda.Kata kunci: kanker payudara, metastasis, tulang, karakteristik klinikopatologik

scholarly journals Breast Subtypes and Prognosis of Breast Cancer Patients With Initial Bone Metastasis: A Population-Based Study

2020 ◽  
Vol 10 ◽  
Author(s):  
Deyue Liu ◽  
Jiayi Wu ◽  
Caijin Lin ◽  
Lisa Andriani ◽  
Shuning Ding ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Metastatic Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Risk Groups ◽  
Population Based ◽  
Breast Cancer Patients

BackgroundMetastatic breast cancer (MBC) is a highly heterogeneous disease and bone is one of the most common metastatic sites. This retrospective study was conducted to investigate the clinical features, prognostic factors and benefits of surgery of breast cancer patients with initial bone metastases.MethodsFrom 2010 to 2015, 6,860 breast cancer patients diagnosed with initial bone metastasis were analyzed from Surveillance, Epidemiology, and End Results (SEER) database. Univariate and Multivariable analysis were used to identify prognostic factors. A nomogram was performed based on the factors selected from cox regression result. Survival curves were plotted according to different subtypes, metastatic burdens and risk groups differentiated by nomogram.ResultsHormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) positive patients showed the best outcome compared to other subtypes. Patients of younger age (<60 years old), white race, lower grade, lower T stage (<=T2), not combining visceral metastasis tended to have better outcome. About 37% (2,249) patients received surgery of primary tumor. Patients of all subtypes could benefit from surgery. Patients of bone-only metastases (BOM), bone and liver metastases, bone and lung metastases also showed superior survival time if surgery was performed. However, patients of bone and brain metastasis could not benefit from surgery (p = 0.05). The C-index of nomogram was 0.66. Cutoff values of nomogram point were identified as 87 and 157 points, which divided all patients into low-, intermediate- and high-risk groups. Patients of all groups showed better overall survival when receiving surgery.ConclusionOur study has provided population-based prognostic analysis in patients with initial bone metastatic breast cancer and constructed a predicting nomogram with good accuracy. The finding of potential benefit of surgery to overall survival will cast some lights on the treatment tactics of this group of patients.

Mechanisms of bone metastasis (BM) growth in patients with metastatic breast cancer (MBC): An exploratory study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1102-1102 ◽  
Author(s):  
W. S. Ooi ◽  
S. Popovic ◽  
M. Kalina ◽  
K. Harriette ◽  
G. Singh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Strategies ◽  
Bone Destruction ◽  
Metastatic Breast ◽  
Treated Group ◽  
Normal Breast ◽  
Primary Cancer ◽  
Comparison Results ◽  
Skeletal Related Events ◽  
Novel Treatment Strategies

1102 Background: The benefits of bisphosphonates (BPs) in reducing or delaying skeletal related events (SREs) in patients with BM have been attributed to their potent osteoclast (OC) inhibiting effect. However, despite the use of modern systemic anti-cancer therapy including potent BPs, many patients with BM continue to suffer from the consequences of their bone disease. An improved understanding of the basic mechanisms of bone destruction would allow further appropriate targeted treatment strategies to be developed. Methods: Archival paraffin embedded BM specimens from patients with MBC were examined for expression of OCs, receptor activator of nuclear factor kappa B (RANK), RANK Ligand (RANKL) and Osteoprotegerin (OPG). Histological specimens were also available for primary breast cancer, lymph node (LN) metastasis, normal breast and bone tissues for comparison. Results: BM specimens were available for 20 BP naïve pts and 2 pts treated with BP. OCs were significantly increased in the BM of the BP naive group compared to controls. There were no OCs seen in the BP treated group. RANK was expressed on tumor cells (TCs) in the both bone and nodal metastases but not on the primary cancer cells. It is also expressed on the OCs which were present in both BM and normal bone. While RANKL was absent in TCs, it was strongly expressed in all stromal cells (SCs) in all specimens and in osteoblasts. The OPG, while present in TCs of the BM and LN metastases, is not detected in the primary cancer. Conclusion: The mechanism of bone destruction in MBC are not fully understood and are clearly multifactorial. OCs may not be the singular obligatory factor for osteolysis in BM. Further investigation of various inhibitors of the RANK/RANKL/OPG pathways, may allow novel treatment strategies to be developed. No significant financial relationships to disclose.

Prognosis of breast cancer patients with initial bone metastasis: A population-based study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13081-e13081
Author(s):  
Deyue LIU ◽  
Jiayi Wu ◽  
Li Zhu
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Metastatic Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Patients ◽  
Risk Group ◽  
Metastatic Breast ◽  
Population Based ◽  
Breast Cancer Patients

e13081 Background: Metastatic breast cancer (MBC) is a highly heterogeneous disease and bone is one of the most common metastatic sites. This retrospective study was conducted to investigate the clinical features, prognostic factors and benefits of surgery of breast cancer patients with initial bone metastases. Methods: From 2010 to 2015, 6860 breast cancer patients diagnosed with initial bone metastasis were analysed from Surveillance, Epidemiology, and End Results (SEER) database. Univariate and Multivariable analysis were used to identify prognostic factors. A nomogram was performed based on the factors selected from cox regression result. Survival curves were plotted according to different subtypes, metastatic burdens and risk group differentiated by nomogram. Results: Hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) positive patients showed the best outcome compared to other subtypes. Patients of younger age ( < 60 years old), white race, lower grade, lower T stage ( < = T2), not combining organ metastasistend to have better outcome. About 37% (2249) patients received surgery of primary tumor. Patients of all subtypes can benefit from surgery. Patients of bone-only metastases (BOM), bone and liver metastases, bone and lung metastases also showed superior survival time if surgery is performed. While patients of bone and brain patients cannot benefit from surgery (p = 0.05). The C-index of nomogram is 0.68. A cutoff value of nomogram point was identified by ROC curve as 93 points, which divided all patients into low-risk group and high-risk group. Patients of both groups showed better overall survival when receiving surgery. Conclusions: Our study has provided population-based nomogram in patients with initial bone metastatic breast cancer. The finding of potential benefit of surgery to overall survival will cast some light on the treatment tactics of this group of patients.

scholarly journals ANGPTL2 increases bone metastasis of breast cancer cells through enhancing CXCR4 signaling

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Tetsuro Masuda ◽  
Motoyoshi Endo ◽  
Yutaka Yamamoto ◽  
Haruki Odagiri ◽  
Tsuyoshi Kadomatsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastasis ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Metastatic Breast ◽  
Cxcr4 Expression ◽  
Breast Cancer Patients

Abstract Bone metastasis of breast cancer cells is a major concern, as it causes increased morbidity and mortality in patients. Bone tissue-derived CXCL12 preferentially recruits breast cancer cells expressing CXCR4 to bone metastatic sites. Thus, understanding how CXCR4 expression is regulated in breast cancer cells could suggest approaches to decrease bone metastasis of breast tumor cells. Here, we show that tumor cell-derived angiopoietin-like protein 2 (ANGPTL2) increases responsiveness of breast cancer cells to CXCL12 by promoting up-regulation of CXCR4 in those cells. In addition, we used a xenograft mouse model established by intracardiac injection of tumor cells to show that ANGPTL2 knockdown in breast cancer cells attenuates tumor cell responsiveness to CXCL12 by decreasing CXCR4 expression in those cells, thereby decreasing bone metastasis. Finally, we found that ANGPTL2 and CXCR4 expression levels within primary tumor tissues from breast cancer patients are positively correlated. We conclude that tumor cell-derived ANGPTL2 may increase bone metastasis by enhancing breast tumor cell responsiveness to CXCL12 signaling through up-regulation of tumor cell CXCR4 expression. These findings may suggest novel therapeutic approaches to treat metastatic breast cancer.

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