Purpose: This study was aimed at detecting and characterizing circulating tumor cells (CTC) before and after neoadjuvant therapy (NT) in the peripheral blood of patients with breast cancer. Experimental Design: The clinical trial GeparQuattro incorporated NT approaches (epirubicin/cyclophosphamide prior to randomization to docetaxel alone, docetaxel in combination with capecitabine, or docetaxel followed by capecitabine) and additional trastuzumab treatment for patients with HER2-positive tumors. We used the Food and Drug Administration–approved CellSearch system for CTC detection and evaluation of HER2 expression and developed HER2 immunoscoring for CTC. Results: We detected ≥1 CTC/7.5 mL in 46 of 213 patients (21.6%) before NT and in 22 of 207 patients (10.6%) after NT (P = 0.002). Twenty (15.0%) initially CTC-positive cases were CTC-negative after NT, whereas 11 (8.3%) cases were CTC-positive after NT, although no CTC could be found before NT. CTC detection did not correlate with primary tumor characteristics. Furthermore, there was no association between tumor response to NT and CTC detection. HER2-overexpressing CTC were observed in 14 of 58 CTC-positive patients (24.1%), including 8 patients with HER2-negative primary tumors and 3 patients after trastuzumab treatment. CTC scored HER2-negative or weakly HER2-positive before or after NT were present in 11 of 21 patients with HER2-positive primary tumors. HER2 overexpression on CTC was restricted to ductal carcinomas and associated with high tumor stage (P = 0.002). Conclusion: CTC number was low in patients with primary breast cancer. The decrease in CTC incidence during treatment was not correlated with standard clinical characteristics and primary tumor response. Information on the HER2 status of CTC might be helpful for stratification and monitoring of HER2-directed therapies. Clin Cancer Res; 16(9); 2634–45. ©2010 AACR.

Purpose: The prognostic value of circulating tumor cells (CTC) detected in breast cancer patients is currently under debate. Different time points of blood collections and various CTC assays have been used in the past decades. Here, we conducted the first comprehensive meta-analysis of published literature on the prognostic relevance of CTC, including patients with early and advanced disease. Experimental Design: A comprehensive search for articles published between January 1990 and January 2012 was conducted; reviews of each study were conducted and data were extracted. The main outcomes analyzed were overall survival (OS) and disease-free survival (DFS) in early-stage breast cancer patients, as well as progression-free survival (PFS) and OS in metastatic breast cancer patients. Pooled hazard ratio (HR) and 95% confidence intervals (CIs) were calculated using the random and the fixed-effects models. Subgroup and sensitivity analyses were also conducted. Results: Forty-nine eligible studies enrolling 6,825 patients were identified. The presence of CTC was significantly associated with shorter survival in the total population. The prognostic value of CTC was significant in both early (DFS: HR, 2.86; 95% CI, 2.19–3.75; OS: HR, 2.78; 95% CI, 2.22–3.48) and metastatic breast cancer (PFS: HR, 1.78; 95% CI, 1.52–2.09; OS: HR, 2.33; 95% CI, 2.09–2.60). Further subgroup analyses showed that our results were stable irrespective of the CTC detection method and time point of blood withdrawal. Conclusion: Our present meta-analysis indicates that the detection of CTC is a stable prognosticator in patients with early-stage and metastatic breast cancer. Further studies are required to explore the clinical utility of CTC in breast cancer. Clin Cancer Res; 18(20); 5701–10. ©2012 AACR.

Progression to severe disease is a difficult problem in treating coronavirus disease 2019 (COVID‐19). The purpose of this study is to explore changes in markers of severe disease in COVID‐19 patients. Sixty‐nine severe COVID‐19 patients were included. Patients with severe disease showed significant lymphocytopenia. Elevated level of lactate dehydrogenase (LDH), C‐reactive protein (CRP), ferritin, and D‐dimer was found in most severe cases. Baseline interleukin‐6 (IL‐6) was found to be associated with COVID‐19 severity. Indeed, the significant increase of baseline IL‐6 was positively correlated with the maximal body temperature during hospitalization and with the increased baseline of CRP, LDH, ferritin, and D‐dimer. High baseline IL‐6 was also associated with more progressed chest computed tomography (CT) findings. Significant decrease in IL‐6 and improved CT assessment was found in patients during recovery, while IL‐6 was further increased in exacerbated patients. Collectively, our results suggest that the dynamic change in IL‐6 can be used as a marker for disease monitoring in patients with severe COVID‐19.

The efficacy and safety of chidamide, a new subtype-selective histone deacetylase (HDAC) inhibitor, have been demonstrated in a pivotal phase II clinical trial, and chidamide has been approved by the China Food and Drug Administration (CFDA) as a treatment for relapsed or refractory peripheral T cell lymphoma (PTCL). This study sought to further evaluate the real-world utilization of chidamide in 383 relapsed or refractory PTCL patients from April 2015 to February 2016 in mainland China. For patients receiving chidamide monotherapy (n = 256), the overall response rate (ORR) and disease control rate (DCR) were 39.06 and 64.45%, respectively. The ORR and DCR were 51.18 and 74.02%, respectively, for patients receiving chidamide combined with chemotherapy (n = 127). For patients receiving chidamide monotherapy and chidamide combined with chemotherapy, the median progression-free survival (PFS) was 129 (95% CI 82 to 194) days for the monotherapy group and 152 (95% CI 93 to 201) days for the combined therapy group (P = 0.3266). Most adverse events (AEs) were of grade 1 to 2. AEs of grade 3 or higher that occurred in ≥5% of patients receiving chidamide monotherapy included thrombocytopenia (10.2%) and neutropenia (6.2%). For patients receiving chidamide combined with chemotherapy, grade 3 to 4 AEs that occurred in ≥5% of patients included thrombocytopenia (18.1%), neutropenia (12.6%), anemia (7.1%), and fatigue (5.5%). This large real-world study demonstrates that chidamide has a favorable efficacy and an acceptable safety profile for refractory and relapsed PTCL patients. Chidamide combined with chemotherapy may be a new treatment choice for refractory and relapsed PTCL patients but requires further investigation.

Current studies have shown that long non‐coding RNAs (lncRNAs) may serve as prognostic biomarkers in multiple cancers. Therefore, we postulated that expression patterns of multiple lncRNAs combined into a single signature could improve clinicopathological risk stratification and prediction of overall survival rate for breast cancer patients. Two algorithms, Least Absolute Shrinkage and Selector Operation (LASSO) and Support Vector Machine‐Recursive Feature Elimination (SVM‐RFE), were used to select candidate lncRNAs. Univariate and multivariate Cox regression analyses were employed to construct a seven‐lncRNA signature for breast cancer. Stratified analysis revealed that the signature was significantly associated with multiple clinicopathological risk factors. For clinical use, we developed a nomogram model to predict overall survival and odds of death for breast cancer patients. Single‐sample gene set enrichment analysis (ssGSEA), CIBERSORT algorithm and ESTIMATE method were employed to assess the relative immune cell infiltrations of each sample. Differentially infiltration of immune cells and diverse tumour mutation burden (TMB) scores might give rise to the efficacy of lncRNA signature for predicting the overall survival of patients. Correlation analysis implied that LINC01215 was associated with multiple immune‐related signalling pathways. A seven‐lncRNA prognostic signature is a reliable tool to predict the prognosis of breast cancer patients.

Disulfiram inhibits TGF-β-induced epithelial-mesenchymal transition and stem-like features in breast cancer via ERK/NF-κB/Snail pathway