HER2-low status may predict poor neoadjuvant chemotherapy response in HR-negative breast cancer: a real-world multicenter study.

OBJECTIVE: We aimed to investigate the impact of human epidermal growth factor receptor 2 status (human epidermal growth factor receptor 2-low versus human epidermal growth factor receptor 2-zero) on pathological response to neoadjuvant chemotherapy and survival outcomes in early-stage breast cancer. METHODS: Patients with primary invasive breast cancer received neoadjuvant chemotherapy between July 2018 and July 2021 were identified from six hospitals. The primary efficacy end-point was total pathological complete response. The second short-term efficacy end-points include breast pathological complete response, axillary lymph nodes pathological complete response and the score of Miller-Payne grade. Long-term efficacy end-point was disease-free survival. RESULTS: 429 patients with human epidermal growth factor receptor 2 negative invasive tumors were included, 267 (62.24%) had human epidermal growth factor receptor 2-low tumors. Hormone receptor-positive patients had a higher percentage of human epidermal growth factor receptor 2-low tumors compared to hormone receptor-negative patients (71.97% versus 42.14%). The pathological response rate was significantly lower in human epidermal growth factor receptor 2-low tumors than in human epidermal growth factor receptor 2-zero tumors for total patients in univariate analysis, including the rates of total pathological complete response (5.2% versus 14.2%), breast pathological complete response (6.4% versus 17.3%), nodes pathological complete response (26.3% versus 37.7%) and MP4-5 (21.2% versus 33.8%). Subgroup analysis showed that the rates of total pathological complete response, breast pathological complete response and MP4-5 were also significantly lower in human epidermal growth factor receptor 2-low tumors versus human epidermal growth factor receptor 2-zero tumors in both univariate and multivariate analysis in hormone receptor-negative subgroup. With the median follow-up of 24 months, disease-free survival was comparable between these two subgroups (P = 0.816). CONCLUSIONS: Our results demonstrate that human epidermal growth factor receptor 2-low tumors achieved a significantly lower pathological complete response rate with conventional chemotherapy than those with human epidermal growth factor receptor 2-zero tumors, especially for hormone receptor-negative group. Large, randomized, prospective studies are needed to confirm our data and further evaluate the prognostic value of human epidermal growth factor receptor 2-low expression.

The role of ferroptosis-related genes for overall survival prediction in breast cancer.

BACKGROUND: Ferroptosis is a novel iron-dependent form of cell death, which is implicated in various diseases including cancers. However, the influence of ferroptosis-related genes on the prognosis of breast cancer remains unclear. METHODS: RNA sequencing data of 1053 breast cancer tissue samples and 111 normal tissue samples from The Cancer Genome Atlas (TCGA) were analyzed. Expression levels of 259 ferroptosis-related genes were compared. Gene Ontology (GO) and the Kyoto Gene and Genomic Encyclopedia (KEGG) analyses were conducted on differentially expressed genes. Cox univariate analysis was conducted to explore the potential prognostic biomarkers of breast cancer. Infiltrating immune cell status was assessed. RESULTS: A total of 66 ferroptosis-related genes were differentially expressed in breast cancer tissues. The enriched GO terms included Biological Process (mainly included response to oxidative stress, cellular response to chemical stress, multicellular organismal homeostasis, cofactor metabolic process, response to metal ion, response to steroid hormone, cellular response to oxidative stress, transition metal ion homeostasis, iron ion homeostasis, and cellular iron ion homeostasis), Cellular Component (mainly included apical plasma membrane, early endosome, apical part of cell, lipid droplet, basolateral plasma membrane, blood microparticle, clathrin-coated pit, caveola, astrocyte projection, and pronucleus) and Molecular Function (mainly included iron ion binding, ubiquitin protein ligase binding, oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor, ferric iron binding, aldo-keto reductase (NADP) activity, oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, steroid dehydrogenase activity, alditol:NADP+1-oxidoreductase activity, and alcohol dehydrogenase (NADP+) activity). The enriched KEGG pathway mainly included the HIF-1 signaling pathway, NOD-like receptor signaling pathway, ferroptosis, IL-17 signaling pathway, central carbon metabolism in cancer, PPAR signaling pathway, PD-L1 expression, and PD-1 checkpoint pathway in cancer. Among them, 38 ferroptosis-related genes were significantly associated with the prognosis of breast cancer. The prognostic model was constructed, and breast cancer patients in low-risk group had a better prognosis. In addition, risk score of ferroptosis prognostic model was negatively correlated with B cells (r = -0.063, p = 0.049), CD8+ T cells (r = -0.083, p = 0.010), CD4+ T cells (r = -0.097, p = 0.002), neutrophils (r = -0.068, p = 0.033), and dendritic cells (r = 0.088, p = 0.006). CONCLUSIONS: The ferroptosis pathway plays a key role in breast cancer. Some differentially expressed ferroptosis-related genes can be used as prognostic biomarkers for breast cancer.

Identifying glycolysis-related LncRNAs for predicting prognosis in breast cancer patients.

PURPOSE: Functions associated with glycolysis could serve as targets or biomarkers for therapy cancer. Our purpose was to establish a prognostic model that could evaluate the importance of Glycolysis-related lncRNAs in breast cancer. METHODS: Gene expressions were evaluated for breast cancer through The Cancer Genome Atlas (TCGA) database, and we calculated Pearson correlations to discover potential related lncRNAs. Differentially expressed genes were identified via criteria of FDR < 0.05 and |FC|> 2. Total samples were separated into training and validating sets randomly. Univariate Cox regression identified 14 prognostic lncRNAs in training set. A prognostic model was constructed to evaluate the accuracy in predicting prognosis. The univariate and multivariate Cox analysis were performed to verify whether lncRNA signature could be an independent prognostic factor The signature was validated in validating set. Immune infiltration levels were assessed. RESULTS: Eighty-nine differentially expressed lncRNAs were identified from 420 Glycolysis-related lncRNAs. 14 lncRNAs were correlated with prognosis in training set and were selected to establish the prognostic model. Low risk group had better prognosis in both training (p= 9.025 e -10) and validating (p= 4.272 e -3) sets. The univariate and multivariate Cox analysis revealed that risk score of glycolysis-related lncRNAs (P< 0.001) was an independent prognostic factor in both training and validating sets. The neutrophils (p= 4.214 e -13, r=-0.223), CD4+ T cells (p= 1.833 e -20, r=-0.283), CD8+ T cells (p= 7.641 e -12, r=-0.211), B cells (p= 2.502 e -10, r=-0.195) and dendritic cells (p= 5.14 e -18, r=-0.265) were negatively correlated with risk score of prognostic model. The Macrophage (p= 0.016, r= 0.0755) was positively correlated with the risk score. CONCLUSION: Our study indicated that glycolysis-related lncRNAs had a significant role to facilitate the individualized survival prediction in breast cancer patients, which would be a potential therapeutic target.

Expression and Prognostic Characteristics of m6 A RNA Methylation Regulators in Breast Cancer.

PURPOSE: N6-methyladenosine (m6A) is the most prevalent modification in mRNA methylation which has a wide effect on biological functions. This study aims to figure out the efficacy of m6A RNA methylation regulator-based biomarkers with prognostic significance in breast cancer. PATIENTS AND METHODS: The 23 RNA methylation regulators were firstly analyzed through ONCOMINE, then relative RNA-seq transcriptome and clinical data of 1,096 breast cancer samples and 112 normal tissue samples were acquired from The Cancer Gene Atlas (TCGA) database. The expressive distinction was also showed by the Gene Expression Omnibus (GEO) database. The gene expression data of m6A RNA regulators in human tissues were acquired from the Genotype-Tissue Expression (GTEx) database. The R v3.5.1 and other online tools such as STRING, bc-GeneExminer v4.5, Kaplan-Meier Plotter were applied for bioinformatics analysis. RESULTS: Results from ONCOMINE, TCGA, and GEO databases showed distinctive expression and clinical correlations of m6A RNA methylation regulators in breast cancer patients. The high expression of YTHDF3, ZC3H13, LRPPRC, and METTL16 indicated poor survival rate in patients with breast cancer, while high expression of RBM15B pointed to a better survival rate. Both univariate and multivariate Cox regression analyses revealed that age and risk scores were related to overall survival (OS). Univariate analysis also delineated that stage, tumor (T) status, lymph node (N) status, and metastasis (M) status were associated with OS. From another perspective, Kaplan-Meier Plotter platform showed that the relatively high expression of YTHDF3 and LRPPRC and the relatively low expression of RBM15B, ZC3H13, and METTL16 in breast cancer patients had worse Relapse-Free Survival (RFS). Breast Cancer Gene-Expression Miner v4.5 showed that LRPPRC level was negatively associated with ER and PR expression, while METTL16, RBM15B, ZC3H13 level was positively linked with ER and PR expression. In HER-2 (+) breast cancer patients, the expression of LRPPRC, METTL16, RBM15B, and ZC3H13 were all lower than the HER-2 (-) group. CONCLUSION: The significant difference in expression levels and prognostic value of m6A RNA methylation regulators were analyzed and validated in this study. This signature revealed the potential therapeutic value of m6A RNA methylation regulators in breast cancer.

[Effect of continuous oral health education on elderly patients with chronic periodontitis treated with dual-wavelength laser].

PURPOSE：To explore the clinical effect of continuous oral health education on elderly patients with chronic periodontitis treated with dual wavelength lasers. METHODS: The clinical data of 150 elderly patients with chronic periodontitis treated with dual-wavelength laser in Shanghai Ninth People's Hospital between March 2016 and March 2018 were analyzed and divided into 2 groups according to the different intervention plans applied. Seventy-five cases receiving routine oral hygiene education were taken as the control group, and the other 75 patients receiving continuous oral health education were set as the experimental group. Oral behavior, gingival index and dental plaque index in the two groups were analyzed and compared using SPSS 21.0 software package. RESULTS: The proportions of patients with correct brushing, taking regular oral examination and maintenance, and keeping good oral habits in the experimental were 97.33%, 93.33% and 92.00%, respectively, which were significantly higher than those in the control group (P<0.05). The gingival index and dental plaque index 3 and 6 months after intervention were (1.24±0.14) and (1.08±0.10), (1.50±0.10) and (1.69±0.26), respectively in the experimental group, which were significantly lower than those in the control group (P<0.05). CONCLUSIONS: For elderly patients with chronic periodontitis treated with dual-wavelength laser therapy, application of continuous oral health education can improve their oral behavior and periodontal status, therefore is worthwhile to be popularized in clinical application.

Dexamethasone-sparing regimen is an effective and safe alternative in overall antiemetic protection: A systematic review and meta-analysis.

OBJECTIVE: We performed a meta-analyisis to evaluate the efficacy of maintenance dexamethasone against acute or delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately or highly emetic risk chemotherapy regimen. METHODS: PubMed, Embase, and Cochrane Library were searched for eligible studies. Data comparing maintenance dexamethasone with single-dose dexamethasone during the acute, delayed, and overall phase of CINV were extracted. Overall risk ratio (RR) was used to estimate the efficacy and adverse effects. RESULTS: Nine studies were included. In delayed phase, maintenance dexamethasone has similar efficacy to single-dose dexamethasone for no emetic episodes (RR, 1.06; 95% confidence interval [CI], 1.00-1.14), complete response (RR, 1.04; 95% CI, 0.98-1.11), complete control (RR, 1.07; 95% CI, 0.98-1.16), and total control (RR, 1.06; 95% CI, 0.91-1.23). In overall phase, maintenance dexamethasone has similar efficacy to single-dose dexamethasone for no emetic episodes (RR, 1.02; 95% CI, 0.94-1.11), complete response (RR, 1.02; 95% CI, 0.95 -1.09), complete control (RR, 1.03; 95% CI, 0.94-1.13), total control (RR, 1.05; 95% CI, 0.90-1.23), and no rescue medication (RR, 1.07; 95% CI, 0.97-1.19). Maintenance dexamethasone was only superior to single-dose dexamethasone for no rescue medication during delayed phase (RR, 1.10; 95% CI, 1.01-1.21, P = .034). The incidence of hiccup was observed higher in maintenance dexamethasone group (RR = 3.16, 95% CI, 1.12-8.92). CONCLUSION: The single-dose dexamethasone regimen offers high and similar overall control of symptoms as the maintenance dexamethasone regimen in this population. Multiple-day dexamethasone was suitable for patients who used rescue medication during the delayed phase.

TGF-ß1 gene silencing can enhances the sensitivity of breast cancer to cisplatin partially by restraining the occurrence of EMT.

Breast cancer is one of the most common gynecological malignant tumors, the main reason of treatment failure is distant metastasis and local recurrence. TGF-ß1 as a versatile polypeptide molecule plays an important role in inducing EMT to promote tumor invasion and metastasis. This study aims to investigate the effect of TGF-ß1 on cisplatin (DDP) inhibiting the proliferation, migration and invasion of breast cancer and its correlation with EMT. TGF-ß1 siRNA were transfected into MCF-7 cells. The cell morphology, proliferation, migration and invasion ability changes were detected by inverted microscope, clone formation assay, cell adhesion assay and Transwell Chamber Invasion. The expression of E-cadherin, vimentin, α-SMA were detected by Western blot. The results showed that TGF-ß1 siRNA were transfected into MCF-7 cells successfully (P<0.05). The inhibitory activity of cisplatin on cell proliferation, migration and invasion of breast cancer were significantly enhanced after TGF-ß1 siRNA transfection (P<0.05). The expression of E-cadherin was up-regulated, and vimentin and α-SMA were down-regulated with TGF-ß1 siRNA transfection (P<0.05). Therefore, we concluded that TGF-ß1 gene silencing can enhance the sensitivity of breast cancer to cisplatin on proliferation, migration and invasion partially by restraining the occurrence of EMT.

Role of Magnetic Resonance Imaging in Detection of Pathologic Complete Remission in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy: A Meta-analysis.

Pathologic complete remission after neoadjuvant chemotherapy has a role in guiding the management of breast cancer. The present meta-analysis examined the accuracy of contrast-enhanced magnetic resonance imaging (CE-MRI) and diffusion-weighted magnetic resonance imaging (DW-MRI) in detecting the response to neoadjuvant chemotherapy and compared CE-MRI with ultrasonography, mammography, and positron emission tomography/computed tomography (PET/CT). Medical subject heading terms and related keywords were searched to generate a compilation of eligible studies. The pooled sensitivity, specificity, diagnostic odds ratio, area under summary receiver operating characteristic curve (AUC), and Youden index (Q* index) were used to estimate the diagnostic efficacy of CE-MRI, DW-MRI, ultrasonography, mammography, and PET/CT. A total of 54 studies of CE-MRI and 8 studies of DW-MRI were included. The overall AUC and the Q* index values for CE-MRI and DW-MRI were 0.88 and 0.94 and 0.80 and 0.85, respectively. According to the summary receiver operating characteristic curves, CE-MRI resulted in a higher AUC value and Q* index compared with ultrasonography and mammography but had values similar to those of DW-MRI and PET/CT. CE-MRI accurately assessed pathologic complete remission in specificity, and PET/CT and DW-MRI accurately assessed pathologic complete remission in sensitivity. The present meta-analysis indicates that CE-MRI has high specificity and DW-MRI has high sensitivity in predicting pathologic complete remission after neoadjuvant chemotherapy. CE-MRI is more accurate than ultrasonography or mammography. Additionally, PET/CT is valuable for predicting pathologic complete remission. CE-MRI, combined with PET/CT or DW-MRI, might allow for a more precise assessment of pathologic complete remission.