Dataset Information

Analysis of Prognostic Factors Affecting the Brain Metastases Free Survival and Survival After Brain Metastases in Breast Cancer.

ABSTRACT: This study aimed to analyze the factors affecting brain metastases free survival (BMFS) and the survival after brain metastases (SABM). The data of 215 patients with breast cancer brain metastases (BCBM) in Sun Yat-sen University Cancer Center from January 2000 to August 2017 were retrospectively analyzed. The clinicopathological features of BCBM were analyzed, and their effects on BMFS and SABM were analyzed by univariate and multivariate COX regression. Finally, it was analyzed whether the receptor status of the brain metastases and the primary lesions were consistent. The median age of the entire cohort was 46 years old. The median BMFS, SABM and overall survival were 31, 9 and 44.2 months, respectively. Clinical stage, molecular subtypes and bone metastasis were independent prognostic factors affecting BMFS. TNM stage IV (HR, 4.99 [95% CI, 2.13-11.7]) and triple negative subtype (HR, 2.06 [95% CI, 1.35-3.14]) was significantly associated with shorter BMFS, but the presence of bone metastases (HR, 0.63 [95% CI, 0.45-0.88]) was a favorable factor for BMFS. Molecular subtypes, resection of BCBM and whole brain radiotherapy (WBRT) were independent factors for SABM. The triple negative subtype (HR, 2.02[95% CI, 1.12-3.64]) was significantly associated with shorter SABM. However, resection of BCBM (HR, 0.31 [95% CI, 0.15-0.65]) and WBRT (HR, 0.57 [95% CI, 0.35-0.93]) were independent factors in improving SABM. The conversion rate of ER was 11.1%, PR was 29.6%, and HER2 was 3.7% between paired breast cancer and brain metastases. BMFS and SABM have different influencing factors. Resection of BCBM and WBRT can significantly improve SABM. The frequency of HER2 status changes between the paired BCBM and the primary lesions is low.

SUBMITTER: Xiao W

PROVIDER: S-EPMC7145983 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Analysis of Prognostic Factors Affecting the Brain Metastases Free Survival and Survival After Brain Metastases in Breast Cancer.

Xiao Weikai W Li Xuerui X Yang Anli A Chen Bo B Zheng Shaoquan S Zhang Guochun G Deng Wenju W Liao Ning N

Frontiers in oncology 20200403

This study aimed to analyze the factors affecting brain metastases free survival (BMFS) and the survival after brain metastases (SABM). The data of 215 patients with breast cancer brain metastases (BCBM) in Sun Yat-sen University Cancer Center from January 2000 to August 2017 were retrospectively analyzed. The clinicopathological features of BCBM were analyzed, and their effects on BMFS and SABM were analyzed by univariate and multivariate COX regression. Finally, it was analyzed whether the rec ...[more]

PMID: 32309214

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Project description:Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use.

Project description:BackgroundThe analysis of disease-free survival and related factors leads to a better understanding of the patient's condition and recurrence-related characteristics and provides a basis for more appropriate treatment guidance. In this study, we aimed to investigate the role of prognostic factors on disease-free survival in breast cancer with a quantile regression model.MethodsThis retrospective study was conducted by reviewing data obtained from 2056 breast cancer patients. Age at diagnosis and education status, tumor size, lymph node ratio, tumor grade, estrogen receptor and progesterone receptor, type of surgery, use of radiotherapy, chemotherapy, and hormone therapy were the prognosis factors considered in this study. A quantile regression model was used to investigate prognostic factors of disease-free survival in breast cancer.ResultsDisease recurrence was verified in 251 (13.9%) women, and 39 (0.02%) women died before experience recurrence. The 10th percentile of disease-free survival for patients with the hormone therapy was 23.85 months greater than patients who did not receive this treatment (P value < .001). In the examination of the tumor size, the 10th and 20th percentiles of disease-free survival for patients with tumor size > 5 cm were 31.06 and 27 months less than patients with the tumor size < 2 cm, respectively (P value = .006 and .021, respectively). Compared with grade 1 tumors, the 10th and 20th percentiles of disease-free survival for patients with grade 3 tumors decreased 30.11 and 38.32 months, respectively (P value < .001 and .038, respectively). The 10th and 20th percentiles of disease-free survival decreased 28.16 and 45.32 months with a 1 unit increase in lymph node ratio, respectively (P value = .032 and .032, respectively).ConclusionsAmong the prognostic factors, tumor size, grade, and lymph node ratio showed a close relationship with disease-free survival in breast cancer. The findings indicated that developing public screening and educational programs through the health care system with more emphasis on low-educated women is needed among Iranian women.

Project description:BackgroundLiver metastasis is a significant adverse predictor of overall survival (OS) among breast cancer patients. The purpose of this study was to determine the risk and prognostic factors of breast cancer with liver metastases (BCLM).MethodsData on 311,573 breast cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database and 1728 BCLM patients from Fudan University Shanghai Cancer Center (FUSCC) were included. Logistic regression was used to identify risk factors for liver metastasis. Cox proportional hazards regression model was adopted to determine independent prognostic factors in BCLM patients.ResultsYoung age, invasive ductal carcinoma, higher pathological grade, and subtype of triple-negative and human epidermal growth factor receptor 2 positive (HER2+) were risk factors for developing liver metastasis. The median OS after liver metastasis was 20.0 months in the SEER database and 27.3 months in the FUSCC dataset. Molecular subtypes also played a critical role in the survival of BCLM patients. We observed that hormone receptor-positive (HR+)/HER2+ patients had the longest median OS (38.0 for SEER vs. 34.0 months for FUSCC), whereas triple-negative breast cancer had the shortest OS (9.0 vs. 15.6 months) in both SEER and FUSCC. According to the results from the FUSCC, the subtype of HR+/HER2+ (hazard ratio (HR) = 2.62; 95% confidence interval (CI) = 1.88-3.66; P < 0.001) and HR-/HER2+ (HR = 3.43; 95% CI = 2.28-5.15; P < 0.001) were associated with a significantly increased death risk in comparison with HR+/HER2- patients if these patients did not receive HER2-targeted therapy. For those who underwent HER2-targeted therapy, however, HR+/HER2+ subtype reduced death risk compared with HR+/HER2- subtype (HR = 0.74; 95% CI = 0.58-0.95; P < 0.001).ConclusionsBreast cancer patients at a high risk for developing liver metastasis deserve more attention during the follow-up. BCLM patients with HR+/HER2+ subtype displayed the longest median survival than HR+/HER2- and triple-negative patients due to the introduction of HER2-targeted therapy and therefore it should be recommended for HER2+ BCLM patients.

Project description:PurposeThe prognosis of breast cancer (BC) patients who develop into brain metastases (BMs) is very poor. Thus, it is of great significance to explore the etiology of BMs in BC and identify the key genes involved in this process to improve the survival of BC patients with BMs.Patients and methodsThe gene expression data and the clinical information of BC patients were downloaded from TCGA and GEO database. Differentially expressed genes (DEGs) in TCGA-BRCA and GSE12276 were overlapped to find differentially expressed metastatic genes (DEMGs). The protein-protein interaction (PPI) network of DEMGs was constructed via STRING database. ClusterProfiler R package was applied to perform the gene ontology (GO) enrichment analysis of DEMGs. The univariate Cox regression analysis and the Kaplan-Meier (K-M) curves were plotted to screen DEMGs associated with the overall survival and the metastatic recurrence survival, which were identified as the key genes associated with the BMs in BC. The immune infiltration and the expressions of immune checkpoints for BC patients with brain relapses and BC patients with other relapses were analyzed respectively. The correlations among the expressions of key genes and the differently infiltrated immune cells or the differentially expressed immune checkpoints were calculated. The gene set enrichment analysis (GSEA) of each key gene was conducted to investigate the potential mechanisms of key genes involved in BC patients with BMs. Moreover, CTD database was used to predict the drug-gene interaction network of key genes.ResultsA total of 154 DEGs were identified in BC patients at M0 and M1 in TCGA database. A total of 667 DEGs were identified in BC patients with brain relapses and with other relapses. By overlapping these DEGs, 17 DEMGs were identified, which were enriched in the cell proliferation related biological processes and the immune related molecular functions. The univariate Cox regression analysis and the Kaplan-Meier curves revealed that CXCL9 and GPR171 were closely associated with the overall survival and the metastatic recurrence survival and were identified as key genes associated with BMs in BC. The analyses of immune infiltration and immune checkpoint expressions showed that there was a significant difference of the immune microenvironment between brain relapses and other relapses in BC. GSEA indicated that CXCL9 and GPR171 may regulate BMs in BC via the immune-related pathways.ConclusionOur study identified the key genes associated with BMs in BC patients and explore the underlying mechanisms involved in the etiology of BMs in BC. These findings may provide a promising approach for the treatments of BC patients with BMs.

Dataset Information

Analysis of Prognostic Factors Affecting the Brain Metastases Free Survival and Survival After Brain Metastases in Breast Cancer.

Publications

Analysis of Prognostic Factors Affecting the Brain Metastases Free Survival and Survival After Brain Metastases in Breast Cancer.

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