Pathological complete response and prognosis after neoadjuvant chemotherapy in patients with HER2-low breast cancer.

BACKGROUND: The development of novel human epidermal growth factor receptor 2 (HER2) antibody drug conjugates brings encouraging opportunities for the treatment of HER2-low breast cancer. In this study, we investigated the clinical factors and prognosis of HER2-low breast cancer after neoadjuvant chemotherapy (NAC). METHODS: Data from patients diagnosed with HER2-zero or HER2-low breast cancer at a single center between January 2017 and December 2021 who underwent NAC followed by surgery were retrospectively reviewed. HER2 status was detected by immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH), and classified as HER2-zero (IHC 0), HER2-low (IHC 1+ or IHC 2+ and FISH-), and HER2-positive (IHC 3+ or IHC 2+ and FISH+). Baseline characteristics were analyzed and compared between the HER2-low and HER2-zero groups. Survival outcomes were analyzed using the Kaplan-Meier method with the log-rank test and Cox proportional-hazards regression analysis. RESULTS: The sample comprised 132 patients with HER2-zero [n = 62 (47.0 %)] and HER2-low [n = 70 (53.0 %)] breast cancer. Relative to the HER2-zero group, the HER2-low group contained larger proportions of patients with hormone receptor (HR) positivity (37.1 % vs. 75.7 %, P < 0.001) and low nuclear grades and Ki-67 indices (both P < 0.05). The pathological complete response (pCR) rate was significantly lower in the HER2-low group than in the HER2-zero group (20.0 % vs. 37.1 %, P = 0.03). At the final follow-up [median 20 (range 4-66) months], patients with HER2-low status had significantly favorable disease-free survival (DFS) and overall survival (OS) outcomes relative to those with HER2-zero status (87.1 % vs. 71.0 %, P = 0.02 and 94.3 % vs. 82.3 %, P = 0.02, respectively). HER2-low status and pCR were independent prognostic factors for DFS [hazard ratio (HR) = 0.31, 95 % confidence interval (CI) 0.13-0.75, P = 0.009 and HR = 0.08, 95 % CI 0.01-0.67, P = 0.02, respectively]. CONCLUSION: This analysis revealed that HER2-low status is associated significantly with HR positivity and low nuclear grades, Ki-67 indices, and pCR rate. It is also associated with favorable DFS and OS outcomes after NAC. HER2-low status and pCR are independent prognostic factors for DFS.

Protective Effects of Lixisenatide against Lipopolysaccharide-Induced Inflammation Response in MAC-T Bovine Mammary Epithelial Cells: A Therapeutic Implication in Mastitis.

Mastitis is acute inflammation caused by microbial infections in the mammary glands. This disease is extremely harmful to lactating mothers. The preferred clinical strategy is antibiotic treatment, but this method results in resistance and side effects. Lixisenatide, a kind of glucagon-like peptide-1 (GLP-1) receptor agonist, is typically used for the treatment of type II diabetes. It is unknown whether lixisenatide possesses a beneficial role in mastitis. In the current study, we assessed the protective effects of lixisenatide against lipopolysaccharide (LPS) stimulation in MAC-T bovine mammary epithelial cells (MECs). Our findings show that lixisenatide attenuated LPS-induced oxidative stress by reducing reactive oxygen species (ROS) production and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases-1 (NOX-1) expression in MAC-T MECs. Additionally, lixisenatide inhibited LPS-induced expression and secretion of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interleukin 1ß (IL-1ß). We also found that lixisenatide suppressed LPS-induced expression of matrix metalloproteinase 2 (MMP-2) and metalloproteinase 9 (MMP-9), and reduced the expression of toll-like receptor 4 (TLR4) (a typical receptor of LPS), its downstream molecule myeloid differentiation factor 88 (MyD88), and the phosphorylation of TGF ß-activated kinase 1 (TAK1). Notably, lixisenatide decreased the nuclear levels of nuclear factor-κB (NF-κB) and its transcriptional activity. These findings suggest that lixisenatide might become a possible therapeutic agent for the treatment of mastitis by weakening oxidative stress and the inflammatory response in MECs.

Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta-Analysis.

BACKGROUND: The value of human leukocyte antigen (HLA; also known as major histocompatibility complex) class I expression for the prediction of breast cancer survival outcomes remains unclear. We conducted a meta-analysis to explore the prognostic significance of this expression. MATERIALS AND METHODS: We searched electronic databases to identify reports on associations of HLA class I protein or mRNA expression with survival outcomes and clinicopathological factors in the breast cancer context. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were used to conduct a quantitative meta-analysis. RESULTS: The sample comprised eight studies involving 3590 patients. Only the classical HLA class Ia (HLA-ABC) molecules studies were included in this meta-analysis. Elevated HLA class I protein expression was found to be significantly related to better disease-free survival (DFS) (HR 0.58, 95% CI 0.35-0.95, P = 0.03), particularly among patients with triple-negative breast cancer (TNBC) (HR 0.31, 95% CI 0.18-0.52, P < 0.001), but not to overall survival. It was also associated with estrogen receptor (ER) negativity (OR 1.71, 95% CI 1.24-2.35, P = 0.001), progesterone receptor (PR) negativity (OR 1.49, 95% CI 1.22-1.81, P < 0.001), human epidermal growth factor receptor 2 (HER2) positivity (OR 1.51, 95% CI 1.18-1.94, P = 0.001), TNBC (OR 1.68, 95% CI 1.15-2.45, P < 0.01), high Ki-67 indices (OR 2.06, 95% CI 1.62-2.61, P < 0.001), and high nuclear grades (OR 2.67, 95% CI 2.17-3.29, P < 0.001). CONCLUSION: This meta-analysis demonstrated that enhanced HLA class I protein expression is significantly associated with the better DFS of patients with breast cancer, especially TNBC, as well as with ER and PR negativity, HER2 positivity, TNBC, and high Ki-67 indices and nuclear grades. The immune target HLA class I may serve as a prognostic indicator for breast cancer.

NCAPH promotes proliferation as well as motility of breast cancer cells by activating the PI3K/AKT pathway.

Objective: This study aimed to assess the expression of NCAPH in human breast cancer, and to investigate its effects on breast cancer cells. Methods: Bioinformation analysis was performed to analyze the expression of NCAPH in human breast cancer tissues and normal tissues in TCGA database. qPCR and Immunoblot assays were performed to clarify the expression of NCAPH in breast cancer tissues and cell lines, respectively. CCK-8, colony formation, FCM, transwell, and immunoblot assays were performed to reveal the effects of NCAPH on breast cancer proliferation, cell cycle, motility and EMT of breast cancer cells. Additionally, immunoblot assays were performed to investigate the effects of NCAPH on the PI3K/AKT pathway in breast cancer. Results: We found that NCAPH was highly expressed in human breast cancer cell lines. The depletion of NCAPH suppressed the viability of breast cancer cells. Further, we noticed that its downregulation restrained breast cancer cell migration as well as invasion, and the EMT process. Mechanically, we noticed that NCAPH mediated the PI3K/AKT pathway, and therefore contributed to breast cancer progression. Conclusion: In summary, NCAPH has the potential to serve as a breast cancer target.

Prognostic and clinical significance of focal adhesion kinase expression in breast cancer: A systematic review and meta-analysis.

BACKGROUND: The prognostic significance of focal adhesion kinase (FAK) in breast cancer remains controversial. Here, we conducted a meta-analysis to explore the prognostic value of FAK expression in breast cancer. MATERIALS AND METHODS: Possible prognostic significance of protein or mRNA expression of FAK in breast cancer was investigated with searches of electronic databases for relevant publications. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were extracted from eligible studies. RESULTS: A total of eight eligible studies which included 2604 participants were analyzed in this meta-analysis. Increased expression of FAK protein was found to significantly correlate with shorter overall survival (OS) (HR = 1.43, 95% CI: 1.12-1.83; P = 0.004), and not with disease-free survival (HR = 1.31, 95% CI: 0.92-1.85; P = 0.14). Elevated FAK protein expression was also associated with negative estrogen receptor (ER) expression (OR, 1.34; 95% CI, 1.06-1.68; P = 0.01), negative progesterone receptor (PR) expression (OR, 1.54; 95% CI, 1.22-1.93; P < 0.001), positive human epidermal growth factor receptor 2 (HER2) expression (OR, 1.64; 95% CI, 1.28-2.09; P < 0.001), triple-negative breast cancer (TNBC) (OR, 1.57; 95% CI, 1.14-2.17; P = 0.006), high nuclear grade (OR, 1.70; 95% CI, 1.05-2.78; P = 0.03), high Ki-67 expression level (OR, 2.87; 95% CI, 1.94-4.24; P < 0.001), and positive p53 status (OR, 2.28; 95% CI, 1.58-3.29; P < 0.001). CONCLUSION: Our meta-analysis identifies an association between increased FAK protein expression and worse OS among breast cancer patients. Moreover, enhanced FAK expression is associated with negative ER expression, negative PR expression, positive HER2 expression, TNBC, high nuclear grade, high Ki-67 expression level, and positive p53 status in breast carcinoma.

Prognostic and clinical significance of syndecan-1 expression in breast cancer: A systematic review and meta-analysis.

BACKGROUND: The prognostic value of syndecan-1 (SDC1, also called CD138) in breast cancer remains controversial. Therefore, we performed a meta-analysis to assess the clinical significance of SDC1 expression in breast cancer. MATERIALS AND METHODS: Various databases were searched to evaluate possible correlations between SDC1 protein or mRNA expression and prognostic significance in breast cancer. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were applied to perform a quantitative meta-analysis. RESULTS: A total of 1305 breast cancer patients from 9 eligible studies were included in this meta-analysis. Significant associations between elevated SDC1 protein expression and poor disease-free survival (DFS) (HR = 1.55, 95% CI: 1.12-2.14; P = 0.007) and overall survival (OS) (HR = 2.08, 95% CI: 1.61-2.69; P < 0.001) were observed. In addition, enhanced SDC1 protein expression correlated with negative estrogen receptor (ER) expression (OR, 2.38; 95% CI, 1.64-3.44; P < 0.001) and positive human epidermal growth factor receptor 2 (HER2) expression (OR, 1.77; 95% CI, 1.14-2.76; P = 0.01). However, increased SDC1 protein expression did not correlate with relapse-free survival (RFS) (HR = 0.33, 95% CI: 0.03-3.13; P = 0.33). There were no additional significant correlations observed between SDC1 protein expression and other clinical factors, including tumor size, lymph node involvement, nuclear grade, and progesterone receptor (PR) expression. CONCLUSION: The results of this meta-analysis demonstrate that increased SDC1 protein expression in breast cancer is significantly associated with worse prognosis in terms of DFS and OS, and an aggressive phenotype is associated with negative ER expression and positive HER2 expression.

Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for breast cancer patients: An updated meta-analysis of 17079 individuals.

AIMS: This study aimed to evaluate the prognostic effect of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for patients with breast cancer (BC). METHODS: A literature search was performed by searching medical databases. Basic characteristics and prognostic data were extracted from included studies. Primary outcomes, such as overall survival (OS) and disease-free survival (DFS), were synthesized and compared. Subgroup analyses were performed according to pathology, geographical region, cut-off value, and tumor progression. RESULTS: A total of 39 studies comprising 17079 BC patients were included in this meta-analysis. Among them, 28 studies with 142 64 BC patients investigated predicting role of NLR for OS, showing elevated NLR were associated poor prognosis (hazard ratio [HR]: 1.78, 95% confidence interval [CI]: 1.49-2.13, P < 0.001). Twenty-seven studies containing 115 04 patients explored the role of NLR in predicting DFS, showing elevated NLR was associated with poor DFS with HR of 1.60 (95% CI: 1.42-1.96, P < 0.001). Twelve studies explored the role of PLR in predicting OS, showing patients with higher PLR were associated with a significantly worse prognosis with a pooled HR of 1.32 (95% CI: 1.11-1.57, P = 0.002). Eleven studies with 5013 patients shown patients with elevated PLR were associated shorter DFS (HR: 1.43, 95% CI: 1.09-1.86, P = 0.009). Subgroup analyses shown a greater magnitude of association between NLR and OS in triple-negative BC patients than in HER2-positive ones. CONCLUSIONS: Our study suggested that elevated NLR and PLR were associated with poor OS as well as high risk of recurrence for BC patients. Subgroup analyses confirmed the prognostic effect of NLR and PLR in HER2-positive BC patients. As easily accessible parameters, NLR and PLR should be identified as useful biomarkers in the management of BC.

Prognostic and clinicopathological value of CXCL12/SDF1 expression in breast cancer: A meta-analysis.

BACKGROUND: Several studies have demonstrated that stromal cell derived factor-1 (SDF1, also known as CXCL12) expression is a biomarker for breast cancer treatment; however, its significance of prognosis is inconsistent. This study uses a meta-analysis to explore the prognostic value of CXCL12/SDF1 expression in breast cancer. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to November 25, 2017. Studies investigating the correlation between CXCL12/SDF1 expression and survival in breast carcinoma were included. The pooled hazard ratio (HR) and 95% confidence interval (95% CI) was used to assess the prognostic value of CXCL12/SDF1 in breast cancer. The pooled odds radio (OR) and 95% CI was applied to evaluate the relationship between CXCL12/SDF1 expression and the clinical characteristics of breast cancer. RESULTS: Eight eligible studies involving 2205 patients were identified. Higher CXCL12/SDF1 protein expression was associated with better disease-free survival (DFS) (HR, 0.76; 95% CI, 0.68-0.86; P < .0001) and overall survival (OS) (HR, 0.66; 95% CI, 0.49-0.87; P = .004) in breast cancer. Furthermore, higher CXCL12/SDF1 protein expression was associated with positive ER status (OR, 1.92; 95% CI, 1.08-3.45; P = .03), negative HER2 status (OR, 2.64; 95% CI, 1.06-6.59; P = .04), and small tumor size (OR, 2.49; 95% CI, 1.47-4.22; P = .0007) in breast cancer, respectively. However, there were no significant associations between the CXCL12/SDF1 mRNA expression and other prognostic parameters, such as TNM stage, age, PR status, lymph node, and nuclear grade (P > .05 for all). CONCLUSIONS: This present meta-analysis suggests that CXCL12/SDF1 protein expression is a good prognostic biomarker in breast cancer. In addition, the over-expression of CXCL12/SDF1 protein was associated with positive ER status, negative HER2 status and small tumor size.

Prognostic and clinical significance of histone deacetylase 1 expression in breast cancer: A meta-analysis.

BACKGROUND: There are conflicting reports about the role of histone deacetylase 1 (HDAC1) in breast cancer prognosis. Here, we conducted a meta-analysis to investigate the prognostic significance of HDAC1 in breast cancer. MATERIALS AND METHODS: We searched different databases to identify studies evaluating the association between HDAC1 expression and its prognostic value in breast cancer. The pooled hazard ratios (HRs) and odds radios (ORs) with 95% confidence intervals (95% CIs) were calculated from these studies to assess specific correlation. RESULTS: Our meta-analysis of four databases identified 7 eligible studies with 1429 total patients. We found that HDAC1 over-expression did not correlate with disease-free survival (DFS) and overall survival (OS) in breast cancer. Subgroup analysis indicated an association between up-regulated HDAC1 expression and better OS (HR = 0.47, 95% CI: 0.23-0.97; P = 0.04) in Asian breast cancer patients. However, false-positive report probability (FPRP) analysis and trial sequential analysis (TSA) indicated that the results need further validation. Furthermore, HDAC1 over-expression was associated with positive estrogen receptor (ER) expression (OR, 3.30; 95% CI, 1.11-9.83; P = 0.03) and negative human epidermal growth factor receptor 2 (HER2) expression (OR, 1.79; 95% CI, 1.22-2.61; P = 0.003), but there were no significant differences between patients based on age, tumor size, lymph node metastasis, nuclear grade, or progesterone receptor (PR) expression. CONCLUSION: Overall, our meta-analysis demonstrated an association between increased HDAC1 expression and better OS in Asian breast cancer patients. In addition, HDAC1 over-expression correlated with positive ER and negative HER2 expression in breast cancer. However, researches in large patients' randomised controlled trials (RCTs) are needed to confirm the results.

Ebselen protects mitochondrial function and oxidative stress while inhibiting the mitochondrial apoptosis pathway after acute spinal cord injury.

Ebselen is a fat-soluble small molecule and organic selenium compound that regulates the activity of glutathione peroxidase to alleviate mitochondrial oxidative stress and improve mitochondrial function. In the present study, we aimed to investigate the effects of ebselen on mitochondrial oxidative stress response, mitochondrial apotosis, and motor behaviors after spinal cord injury (SCI). We found that ebselen significantly increased the BBB score in motor behavior, thus suggesting a rescue effect of ebselen on motor function after SCI in rats. Meanwhile, we revealed that ebselen can increase glutathione (GSH) content as well as superoxide dismutase (SOD) and catalase (CAT) activities after SCI-this suggests ebselen has an antioxidant effect. Furthermore, the ATP content and Na+-K+-ATPase activity in mitochondria were increased by ebselen after SCI, while the mitochondrial membrane potential (MMP) was decreased by ebselen. The Cytochrome C and Smac release from mitochondria were reduced by ebselen after SCI, thus indicating improved membrane permeability by ebselen. Moreover, the alterations in caspase-3, Bax and Bcl-2 protein expression, as well as the proportion of cell apoptosis were improved by ebselen treatment, which together suggested that ebselen has an inhibitory effect on mitochondrial apotosis pathways after SCI. Taken together, our results suggest that ebselen can inhibit secondary damage caused by spinal cord injury. Indeed it plays a neuroprotective role in spinal cord injury perhaps by improving mitochondrial function and inhibiting the mitochondrial apoptosis pathway.

Prognostic and clinicopathological value of poly (adenosine diphosphate-ribose) polymerase expression in breast cancer: A meta-analysis.

BACKGROUND: Previous studies have shown that the poly (adenosine diphosphate-ribose) polymerase (PARP) level is a promising indicator of breast cancer. However, its prognostic value remains controversial. The present meta-analysis evaluated the prognostic value of PARP expression in breast cancer. MATERIALS AND METHODS: Eligible studies were retrieved from the PubMed, Web of Science, Embase, and Cochrane Library databases through July 20, 2016. Studies investigating PARP expression as well as reporting survival data in breast cancer were included. Two independent reviewers carried out all literature searches. The pooled relative risk (RR) and hazard ratio (HR) with 95% confidence interval (95% CI) were applied to assess the association between PARP expression and the clinicopathological features and survival outcome in breast cancer. RESULTS: A total of 3506 patients from eight eligible studies were included. We found that higher PARP expression indicated a worse clinical outcome in early stage breast cancer, with a HR of 3.08 (95% CI, 1.14-8.29, P = 0.03) for disease-free survival and a HR of 1.82 (95% CI, 1.20-2.76; P = 0.005) for overall survival. Moreover, increased PARP expression was significantly associated with higher nuclear grade (RR, 1.51; 95% CI, 1.12-2.04; P = 0.008) in breast cancer. A similar correlation was detected in triple-negative breast cancer (TNBC; RR, 1.81; 95% CI, 1.04-3.17; P = 0.04). CONCLUSIONS: Our findings indicated that elevated PARP expression correlated with worse prognosis in early stage breast cancer. Furthermore, high PARP expression was associated with higher nuclear grade and TNBC.

Prognostic and clinicopathological value of Twist expression in breast cancer: A meta-analysis.

BACKGROUND: Despite initial indications that the transcription factor Twist could be used as a breast cancer prognostic marker, there still exists some controversy about its reliability. Thus, the aim of the present study was to assess the relationship between Twist expression and prognosis in breast carcinoma. MATERIALS AND METHODS: We identified eligible studies that reported an association between Twist expression and breast cancer prognosis by searching the literature in PubMed, Embase, the Cochrane Library, and Web of Science databases, through June 5, 2017. Studies investigating Twist protein or mRNA expression as well as reporting survival data in breast cancer were included. The pooled hazard ratio (HR) and odds radio (OR) with a 95% confidence interval (95% CI) were used to estimate associations. RESULTS: A total of 2,671 patients from seven included studies were assessed, and the data indicated that increased Twist expression significantly correlated with poor overall survival (OS) (HR, 1.15; 95% CI, 1.00-1.33; P = 0.04) in breast cancer. In addition, we also observed a significant correlation of elevated Twist expression with larger tumor size (OR, 1.92; 95% CI, 1.31-2.81; P = 0.0009), lymph node involvement (OR, 3.81; 95% CI, 1.16-12.54; P = 0.03), higher nuclear grade (OR, 1.45; 95% CI, 1.06-2.00; P = 0.02), and positive human epidermal growth factor receptor 2 (HER2) status (OR, 1.49; 95% CI, 1.06-2.09; P = 0.02). However, no correlation between Twist expression and disease-free survival (DFS), age, estrogen receptor (ER) status, and progesterone receptor (PR) status was observed. CONCLUSIONS: Our results demonstrate that Twist over-expression is a statistically significant indicator of OS in breast cancer. In addition, our meta-analysis shows that increased Twist expression is significantly associated with larger tumor size, lymph node involvement, higher nuclear grade, and positive HER2 status.

Secondary breast carcinoma after completely remitted chronic myeloid leukemia following targeted tyrosine kinase inhibitor therapy.

We describe a rare case of secondary breast carcinoma after chronic myeloid leukemia (CML) in a 56-year-old woman. The patient was treated with hydroxyurea and imatinib for CML and achieved complete remission (she has since been taking imatinib as the maintenance therapy). Four years later, the patient noticed a firm and painless lump in the left breast, which was diagnosed as ductal carcinoma in situ based on a percutaneous biopsy of the mass. Simple resection and sentinel lymph node biopsy of the left breast were then performed. Pathological studies revealed a medium-grade intraductal carcinoma, with local infiltration associated with invasive micropapillary carcinoma. She received adjuvant endocrine therapy with imatinib after surgery. Breast cancer secondary to CML (treated with imatinib and completely remitted) is extremely rare. This report provides evidence to assist in the diagnosis and treatment for this rare manifestation.