Total Brain Irradiation for Metastatic Lesions in Breast Cancer Patients

2021 ◽  
Vol 66 (6) ◽  
pp. 71-74
Author(s):  
A. Balkanov ◽  
V. Metelin ◽  
I. Vasilenko
Keyword(s):  
Breast Cancer ◽  
Survival Rate ◽  
Brain Metastasis ◽  
Cancer Patients ◽  
Time Interval ◽  
Breast Cancer Patients ◽  
Brain Irradiation ◽  
Risk Of Death ◽  
Total Brain ◽  
Breast Cancer Brain Metastasis

Purpose: Brain metastasis (BM) has a significant negative impact on the survival of breast cancer patients. An intensive search is underway for a multi-modal approach to identify the most effective methods of treating such patients. Material and methods: The study included 40 patients with breast cancer who were diagnosed with BM on magnetic resonance imaging (MRI) of the brain. Total brain irradiation (TBI) up to 30 Gy (3 Gy) was used as the main treatment method. The median age was 48 (31–70) years. In 75 % of cases, a nonluminal subtype of breast cancer was found, in 57.5 % of cases–T2 breast cancer, in 70 % of cases–N0-1. Results: The median survival after TBI was 12 months, 6-month survival rate was 70 %, and 12 – month survival rate was 47.5 %. The risk of death was significantly increased (HR=3.309; 95 % CI: 1,184 – 9,250, p=0.023) in patients whose time interval from the manifestation of 1 relapse to BM was ≤24 months. In these patients, the survival was only 9.5 months and was significantly lower (p=0.0136) than in the patients with the same time interval was >24 months – 30 months. Conclusions: It was found that the effectiveness of total brain irradiation in patients with breast cancer brain metastasis is the highest if the time interval from the moment of manifestation of first relapse to brain metastasis is more than 24 months.

scholarly journals Identification of potential genes related to breast cancer brain metastasis in breast cancer patients

2021 ◽  
Author(s):  
Lijian Zhang ◽  
Luxuan Wang ◽  
Hua Yang ◽  
Chunhui Li ◽  
Chuan Fang
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Cancer Patients ◽  
Molecular Mechanisms ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Breast Cancer Patients ◽  
Breast Cancer Brain Metastasis ◽  
Geo Database

Brain metastases (BM) usually develop in breast cancer patients. Thus, the molecular mechanisms of breast cancer brain metastasis (BCBM) are of great importance in designing therapeutic strategies to treat or prevent BCBM. This study attempted to identify novel diagnostic and prognostic biomarkers of BCBM. Two datasets (GSE125989 and GSE100534) were obtained from the Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs) in cases of breast cancer with and without brain metastasis. A total of 146 overlapping DEGs, including 103 up-regulated genes and 43 down-regulated genes, were identified. Functional enrichment analysis showed that these DEGs were mainly enriched for functions including extracellular matrix organization and collagen catabolic fibril organization. Using protein-protein interaction (PPI) and principal component analysis (PCA) analysis, we identified 10 key genes, including LAMA4, COL1A1, COL5A2, COL3A1, COL4A1, COL5A1, COL5A3, COL6A3, COL6A2, and COL6A1. Additionally, COL5A1, COL4A1, COL1A1, COL6A1, COL6A2 and COL6A3 were significantly associated with the overall survival of BC patients. Furthermore, COL6A3, COL5A1, and COL4A1 were potentially correlated with BCBM in human epidermal growth factor 2 (HER2) expression. Additionally, the miR-29 family might participate in the process of metastasis by modulating the cancer microenvironment. Based on datasets in the GEO database, several DEGs have been identified as playing potentially important roles in BCBM in BC patients.

scholarly journals Profiles of ferroptosis-related genes and their prognostic values in patients with breast cancer brain metastasis

2021 ◽  
Author(s):  
Lei Zhu ◽  
Mu Chen ◽  
Bingsong Huang ◽  
Min Liu ◽  
Chunlong Zhong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Cancer Patients ◽  
Risk Group ◽  
Expression Profiles ◽  
Low Risk ◽  
Functional Enrichment ◽  
Breast Cancer Patients ◽  
Cox Regression Analysis ◽  
Breast Cancer Brain Metastasis

Abstract Background Ferroptosis is involved in various cancers. The role of ferroptosis in breast cancer brain metastasis (BCBM) is unclear. This study aimed to explore the ferroptosis-related genes (FRG) expression profiles in BCBM, as well as evaluate the FRG prognostic values in breast cancer patients.Methods Genes expression and clinical data were downloaded from Gene Expression Omnibus (GEO). Functional enrichment analysis was used to investigate the FRG bioinformatics functions. Univariate and multivariate cox regression analysis were performed to explore the independent prognostic factors. The correlation between ferroptosis and immunity was also evaluated. Finally, the FRG and their prognostic values were validated in external cohorts.Results Fourteen significantly different FRG were screened between breast cancer and BCBM tissues. GO and KEGG results showed FRG were enriched in the ferroptosis-related activities. Protein‑protein interaction (PPI) network analysis showed the HMOX1 and TFRC were hub genes. Survival analysis demonstrated HMOX1 and PEBP1 were significantly associated with overall survival (OS) (HR=2.100, P=0.035; HR=0.421, P=0.017 respectively). The KEAP1 and LPCAT3 had prognostic values for relapse-free survival (RFS) (HR=0.745, P=0.002; HR=2.536, P=0.008 respectively). Patients in high-risk group have worse OS and RFS compared with those in low-risk group (P=0.004, 0.021 respectively). Clinical correlation analysis revealed FRG were significantly associated with estrogen receptor (ER) status, progesterone receptor (PgR) status, HER2 and pathological grade in breast cancer patients (all P<0.05). In addition, we also found that immune-related pathways and immune status were different between high and low-risk groups. External cohort results showed FRG were significantly different between breast cancer and BCBM tissues. Survival validation demonstrated ALOX5 and CS were associated with prognosis in breast cancer patients (P=0.044, 0.032 respectively). Conclusions Our study identified the ferroptosis-related genes that may be involved in biology of BCBM, and FRG could serve as prognostic biomarkers in breast cancer patients. New therapy targeting ferroptosis holds probabilities for effective treatment in BCBM patients.

scholarly journals MAT2A Localization and Its Independently Prognostic Relevance in Breast Cancer Patients

2021 ◽  
Vol 22 (10) ◽  
pp. 5382
Author(s):  
Pei-Yi Chu ◽  
Hsing-Ju Wu ◽  
Shin-Mae Wang ◽  
Po-Ming Chen ◽  
Feng-Yao Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Rate ◽  
Protein Expression ◽  
Cancer Patients ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Expression Ratio

(1) Background: methionine cycle is not only essential for cancer cell proliferation but is also critical for metabolic reprogramming, a cancer hallmark. Hepatic and extrahepatic tissues methionine adenosyltransferases (MATs) are products of two genes, MAT1A and MAT2A that catalyze the formation of S-adenosylmethionine (SAM), the principal biological methyl donor. Glycine N-methyltransferase (GNMT) further utilizes SAM for sarcosine formation, thus it regulates the ratio of SAM:S-adenosylhomocysteine (SAH). (2) Methods: by analyzing the TCGA/GTEx datasets available within GEPIA2, we discovered that breast cancer patients with higher MAT2A had worse survival rate (p = 0.0057). Protein expression pattern of MAT1AA, MAT2A and GNMT were investigated in the tissue microarray in our own cohort (n = 252) by immunohistochemistry. MAT2A C/N expression ratio and cell invasion activity were further investigated in a panel of breast cancer cell lines. (3) Results: GNMT and MAT1A were detected in the cytoplasm, whereas MAT2A showed both cytoplasmic and nuclear immunoreactivity. Neither GNMT nor MAT1A protein expression was associated with patient survival rate in our cohort. Kaplan–Meier survival curves showed that a higher cytoplasmic/nuclear (C/N) MAT2A protein expression ratio correlated with poor overall survival (5 year survival rate: 93.7% vs. 83.3%, C/N ratio ≥ 1.0 vs. C/N ratio < 1.0, log-rank p = 0.004). Accordingly, a MAT2A C/N expression ratio ≥ 1.0 was determined as an independent risk factor by Cox regression analysis (hazard ratio = 2.771, p = 0.018, n = 252). In vitro studies found that breast cancer cell lines with a higher MAT2A C/N ratio were more invasive. (4) Conclusions: the subcellular localization of MAT2A may affect its functions, and elevated MAT2A C/N ratio in breast cancer cells is associated with increased invasiveness. MAT2A C/N expression ratio determined by IHC staining could serve as a novel independent prognostic marker for breast cancer.

scholarly journals Surgery for primary tumor benefits survival for breast cancer patients with bone metastases: a large cohort retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhangheng Huang ◽  
Xin Zhou ◽  
Yuexin Tong ◽  
Lujian Zhu ◽  
Ruhan Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Primary Tumor ◽  
Predictive Accuracy ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Risk Of Death ◽  
The Impact

Abstract Background The role of surgery for the primary tumor in breast cancer patients with bone metastases (BM) remains unclear. The purpose of this study was to determine the impact of surgery for the primary tumor in breast cancer patients with BM and to develop prognostic nomograms to predict the overall survival (OS) of breast cancer patients with BM. Methods A total of 3956 breast cancer patients with BM from the Surveillance, Epidemiology, and End Results database between 2010 and 2016 were included. Propensity score matching (PSM) was used to eliminate the bias between the surgery and non-surgery groups. The Kaplan-Meier analysis and the log-rank test were performed to compare the OS between two groups. Cox proportional risk regression models were used to identify independent prognostic factors. Two nomograms were constructed for predicting the OS of patients in the surgery and non-surgery groups, respectively. In addition, calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the performance of nomograms. Result The survival analysis showed that the surgery of the primary tumor significantly improved the OS for breast cancer patients with BM. Based on independent prognostic factors, separate nomograms were constructed for the surgery and non-surgery groups. The calibration and ROC curves of these nomograms indicated that both two models have high predictive accuracy, with the area under the curve values ≥0.700 on both the training and validation cohorts. Moreover, DCA showed that nomograms have strong clinical utility. Based on the results of the X-tile analysis, all patients were classified in the low-risk-of-death subgroup had a better prognosis. Conclusion The surgery of the primary tumor may provide survival benefits for breast cancer patients with BM. Furthermore, these prognostic nomograms we constructed may be used as a tool to accurately assess the long-term prognosis of patients and help clinicians to develop individualized treatment strategies.

Predicting Brain Metastasis in Breast Cancer Patients: Stage Versus Biology

2018 ◽  
Vol 18 (2) ◽  
pp. e187-e195 ◽  
Author(s):  
Hamdy A. Azim ◽  
Raafat Abdel-Malek ◽  
Loay Kassem
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Cancer Patients ◽  
Stage Versus ◽  
Breast Cancer Patients

scholarly journals Stage-Specific Survival Rate of Breast Cancer Patients in Northern Thailand in Accordance with Two Different Staging Systems

2019 ◽  
Vol 20 (9) ◽  
pp. 2699-2706
Author(s):  
Imjai Chitapanarux ◽  
Patumrat Sripan ◽  
Areewan Somwangprasert ◽  
Chaiyut Charoentum ◽  
Wimrak Onchan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Rate ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Northern Thailand ◽  
Staging Systems

scholarly journals CircBCBM1 Promotes Breast Cancer Brain Metastasis via miR-125a/BRD4 Axis

2020 ◽  
Author(s):  
Bo Fu ◽  
Wei Liu ◽  
Peng Li ◽  
Li Pan ◽  
Ke Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Breast Cancer Patients ◽  
Breast Cancer Brain Metastasis ◽  
Tumorigenesis And Progression ◽  
And Migration

Abstract Background: Accumulating evidence indicates that circular RNAs (circRNAs) play critical roles in tumorigenesis and progression of various cancers. We previously identified a novel upregulated circRNA, circBCBM1 (hsa_circ_0001944), in the context of breast cancer brain metastasis. However, the potential biological function and molecular mechanism of circBCBM1 in breast cancer brain metastasis remain largely unknown.Methods: In this reserch, we validated the expression and characterization of circBCBM1 through RT-qPCR, Sanger sequencing, RNase R assay and fluorescence in situ hybridization (FISH). Functional experiments were performed to determine the effect of circBCBM1 on growth and metastasis of 231-BR cells both in vitro and in vivo. The regulatory mechanisms among circBCBM1, miR-125a (has-miR-125a-5p), and BRD4 (bromodomain containing 4) were investigated by RNA immunoprecipitation (RIP), RNA pull-down, luciferase reporter assay and western blot. Results: Our findings demonstrated that circBCBM1 is a stable and cytoplasmic circRNA. Functionally, silencing of circBCBM1 led to decreased proliferation and migration of 231-BR cells whereas elevated circBCBM1 expression showed reverse effects in vitro. These findings were confirmed in vivo in mouse models, as knockdown of circBCBM1 significantly decreased growth and brain metastases of 231-BR cells. Mechanistically, circBCBM1 functions as an endogenous miR-125a sponge to inhibit miR-125a activity, resulting in the upregulation of BRD4 expression and subsequent upregulation of MMP9 (matrix metallopeptidase 9) through Sonic hedgehog (SHH) signaling pathway. Importantly, circBCBM1 was markedly upregulated in the breast cancer brain metastasis cells and clinical tissue and plasma samples; besides, the overexpression of circBCBM1 in primary cancerous tissues was associated with shorter brain metastasis-free survival (BMFS) of breast cancer patients.Conclusions: These findings indicate that circBCBM1 is involved in breast cancer brain metastasis via circBCBM1/miR-125a/BRD4 axis, which sheds light on the pathogenic mechanism of circBCBM1 and provides translational evidence that circBCBM1 may serve as a novel diagnostic or prognostic biomarker and potential therapeutic target for breast cancer brain metastasis.

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