Spindle and kinetochore­associated complex subunit 3 accelerates breast cancer cell proliferation and invasion through the regulation of Akt/Wnt/ß-catenin signaling.

PURPOSE: Spindle and kinetochore­associated complex subunit 3 (SKA3) has recently been identified as a novel regulator of carcinogenesis in multiple types of cancers. However, the function and potential regulatory mechanisms of SKA3 in breast cancer remain poorly understood. The present study was designed to gain a detailed relevance of SKA3 in breast cancer. METHODS: Expression of SKA3 in breast cancer was examined via real-time quantitative PCR, western blotting and immunohistochemistry analysis. Malignant behaviors of breast cancer cells were investigated via cell counting kit-8, cell apoptosis, and transwell invasion assays. The activity of Wnt/ß-catenin signaling was monitored via luciferase reporter assay. The tumorigenicity of breast cancer cells in vivo was assessed via xenograft tumor assay. RESULTS: SKA3 expression was elevated in breast cancer tissue and was correlated with shorter survival rates in breast cancer patients. Knockdown of SKA3 caused marked reductions in cellular proliferation and invasion in breast cancer cells, whereas SKA3 overexpression accelerated proliferation and invasion. Knockdown of SKA3 resulted in decreased Akt and glycogen synthase kinase-3ß phosphorylation, and decreased expression of active ß-catenin, which lead to the inactivation of Wnt/ß-catenin signaling. Inhibition of Akt significantly reversed the SKA3 overexpression-induced activation of Wnt/ß-catenin signaling. Inhibition of Wnt/ß-catenin signaling markedly abrogated SKA3 overexpression-induced tumor-promotion effects, while re-activation of Wnt/ß-catenin signaling significantly reversed SKA3 knockdown-mediated tumor-inhibition effects. Knockdown of SKA3 resulted in a significant decrease in breast cancer tumor formation in vivo. CONCLUSIONS: SKA3 accelerates proliferation and invasion in breast cancer through the modulation of Akt/Wnt/ß-catenin signaling.

Can We Reliably Identify the Pathological Outcomes of Neoadjuvant Chemotherapy in Patients with Breast Cancer? Development and Validation of a Logistic Regression Nomogram Based on Preoperative Factors.

BACKGROUND: Pathological responses of neoadjuvant chemotherapy (NCT) are associated with survival outcomes in patients with breast cancer. Previous studies constructed models using out-of-date variables to predict pathological outcomes, and lacked external validation, making them unsuitable to guide current clinical practice. OBJECTIVE: The aim of this study was to develop and validate a nomogram to predict the objective remission rate (ORR) of NCT based on pretreatment clinicopathological variables. METHODS: Data from 110 patients with breast cancer who received NCT were used to establish and calibrate a nomogram for pathological outcomes based on multivariate logistic regression. The predictive performance of this model was further validated using a second cohort of 55 patients with breast cancer. Discrimination of the prediction model was assessed using an area under the receiver operating characteristic curve (AUC), and calibration was assessed using calibration plots. The diagnostic odds ratio (DOR) was calculated to further evaluate the performance of the nomogram and determine the optimal cut-off value. RESULTS: The final multivariate regression model included age, NCT cycles, estrogen receptor, human epidermal growth factor receptor 2 (HER2), and lymphovascular invasion. A nomogram was developed as a graphical representation of the model and showed good calibration and discrimination in both sets (an AUC of 0.864 and 0.750 for the training and validation cohorts, respectively). Finally, according to the Youden index and DORs, we assigned an optimal ORR cut-off value of 0.646. CONCLUSION: We developed a nomogram to predict the ORR of NCT in patients with breast cancer. Using the nomogram, for patients who are operable and whose ORR is < 0.646, we believe that the benefits of NCT are limited and these patients can be treated directly using surgery.

Major Postoperative Complications in Esophageal Cancer After Minimally Invasive Esophagectomy Compared With Open Esophagectomy: An Updated Meta-analysis.

BACKGROUND: To evaluate the existing literature comparing cardiopulmonary complications after minimally invasive esophagectomy (MIE) with open esophagectomy (OE) and conduct a meta-analysis based on the relevant studies. METHODS: A systematic search for articles was performed in Medline, Embase, Wiley Online Library, and the Cochrane Library. The relative risks or odds ratios (ORs) were calculated by using fixed or random-effects models. The I2 and X2 tests were used to test for statistical heterogeneity. We performed a metaregression for the pulmonary complications with the adenocarcinoma proportion and tumor stage. Publication bias and small-study effects were assessed using Egger's test and Begg's funnel plot. RESULTS: A total of 30,850 participants were enrolled in the 63 studies evaluated in the meta-analysis. Arrhythmia, pulmonary embolism, pulmonary complications, gastric tip necrosis, anastomotic leakage, and vocal cord palsy were chosen as outcomes. The occurrence rate of arrhythmia was significantly lower in patients receiving MIE than in patients receiving OE (OR = 0.69; 95% CI = 0.53-0.89), with heterogeneity (I2 = 30.7%, P = 0.067). The incidence of pulmonary complications was significantly lower in patients receiving MIE (OR = 0.54, 95% CI = 0.45-0.63) but heterogeneity remained (I2 = 72.1%, P = 0.000). The risk of gastric tip necrosis (OR = 1.48, 95% CI = 1.07-2.05) after OE was lower than that after MIE. Anastomotic leakage, pulmonary embolism, and vocal cord palsy showed no significant differences between the two groups. CONCLUSIONS: MIE has advantages over OE, especially in reducing the incidence of arrhythmia and pulmonary complications. Thus, MIE can be recommended as the preferred alternative surgery method for resectable esophageal cancer.

Increased SIX-1 expression promotes breast cancer metastasis by regulating lncATB-miR-200s-ZEB1 axis.

Patients with advanced breast cancer (BC) showed a higher incidence of regional and distant metastases. Sine oculis homeobox homolog 1 (SIX-1) has been confirmed to be a key tumorigenic and metastatic regulator in BC progression. Yet, molecular mechanisms behind SIX-1-induced BC metastases remain largely unknown. Here we found that SIX-1 was frequently up-regulated in BC and correlated with poor outcomes when tested in human BC tissue microarray. Then, we manipulated the expression of SIX-1 by via shRNA-mediated knockdown and lentivirus-mediated overexpression. Transwell assay in vitro and lung metastases model of nude mice in vivo showed that SIX-1 promoted BC cell invasion and migration in vitro, and facilitated metastases in vivo. Mechanistically, SIX-1 could promote the transcription of lncATB, which exerts critical pro-metastatic role in BC by directly binding to the miR-200 family, especially for miR-200c, to induce EMT and promote metastases. In conclusion, SIX-1 exerts its pro-metastatic role in BC through lncATB/miR-200s axis of EMT signalling pathway and could act as an important diagnostic marker as well as a significant therapeutic target for clinically advanced BC.

Nomogram-derived prediction of pathologic complete response (pCR) in breast cancer patients treated with neoadjuvant chemotherapy (NCT).

BACKGROUND: Previous research results on the predictive factors of neoadjuvant chemotherapy (NCT) efficacy in breast cancer are inconsistent, suggesting that the ability of a single factor to predict efficacy is insufficient. Combining multiple potential efficacy-related factors to build a model may improve the accuracy of prediction. This study intends to explore the clinical and biological factors in breast cancer patients receiving NCT and to establish a nomogram that can predict the pathologic complete response (pCR) rate of NCT. METHODS: We selected 165 breast cancer patients receiving NCT from July 2017 to May 2019. Using pretreatment biopsy materials, immunohistochemical studies to assess estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 expression. The correlation between biological markers and pCR was analyzed. These predictors were used to develop a binary logistic regression model with cross-validation and to show the established predictive model with a nomogram. RESULTS: The nomogram for pCR based on lymphovascular invasion, anemia (hemoglobin≤120 g/L), ER, Ki67 expression levels and NCT regimen had good discrimination performance (area under the curve [AUC], 0.758; 95% confidence interval [CI], 0.675-0.841) and calibration coordination. According to the Hosmer-Lemeshow test, the calibration chart showed satisfactory agreement between the predicted and observed probabilities. The final prediction accuracy of cross-validation was 76%. CONCLUSIONS: We developed a nomogram based on multiple clinical and biological covariations that can provide an early prediction of NCT response and can help to quickly assess the individual benefits of NCT.

Unveiling potential drug targets for hyperparathyroidism through genetic insights via Mendelian randomization and colocalization analyses.

Hyperparathyroidism (HPT) manifests as a complex condition with a substantial disease burden. While advances have been made in surgical interventions and non-surgical pharmacotherapy for the management of hyperparathyroidism, radical options to halt underlying disease progression remain lacking. Identifying putative genetic drivers and exploring novel drug targets that can impede HPT progression remain critical unmet needs. A Mendelian randomization (MR) analysis was performed to uncover putative therapeutic targets implicated in hyperparathyroidism pathology. Cis-expression quantitative trait loci (cis-eQTL) data serving as genetic instrumental variables were obtained from the eQTLGen Consortium and Genotype-Tissue Expression (GTEx) portal. Hyperparathyroidism summary statistics for single nucleotide polymorphism (SNP) associations were sourced from the FinnGen study (5590 cases; 361,988 controls). Colocalization analysis was performed to determine the probability of shared causal variants underlying SNP-hyperparathyroidism and SNP-eQTL links. Five drug targets (CMKLR1, FSTL1, IGSF11, PIK3C3 and SLC40A1) showed significant causation with hyperparathyroidism in both eQTLGen and GTEx cohorts by MR analysis. Specifically, phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) and solute carrier family 40 member 1 (SLC40A1) showed strong evidence of colocalization with HPT. Multivariable MR and Phenome-Wide Association Study analyses indicated these two targets were not associated with other traits. Additionally, drug prediction analysis implies the potential of these two targets for future clinical applications. This study identifies PIK3C3 and SLC40A1 as potential genetically proxied druggable genes and promising therapeutic targets for hyperparathyroidism. Targeting PIK3C3 and SLC40A1 may offer effective novel pharmacotherapies for impeding hyperparathyroidism progression and reducing disease risk. These findings provide preliminary genetic insight into underlying drivers amenable to therapeutic manipulation, though further investigation is imperative to validate translational potential from preclinical models through clinical applications.

Prognostic value of pathological nodal burden after neoadjuvant chemotherapy in initially cN0-1 breast cancer patients: a dual-center, 10-year survival analysis.

Background: There is an interest in performing de-escalating axillary surgery after neoadjuvant chemotherapy (NAC). However, the significance of residual axillary node disease after NAC has not been well studied. Objectives: To investigate the pathological residual axillary lymph node tumor burden (ypN) of patients with initial clinical nodal stage cN0-1 breast cancer after NAC and determine its prognostic value. Design: Initial cN0-1 breast cancer patients who received NAC followed by axillary surgery at the First Hospital of Jilin University and the First Affiliated Hospital of Xi'an Jiaotong University between January 2011 and December 2019 were included. Methods: Survival outcomes were compared according to different clinical and pathological stage and nodal response to NAC. The main outcomes were disease-free survival (DFS) and overall survival (OS). Factors associated with survival were defined by Cox regression analysis. Results: A total of 911 patients were included, among whom 260 had cN0 and 651 had cN1 tumors. After NAC, 410 patients were ypN0, and another 501 were ypN+. The median follow-up time was 63 months. There was no significant difference in DFS or OS between the cN0 and cN1 groups in hormone receptor positive (HR+)/human epidermal growth factor receptor 2 positive (HER2+) and HR-/HER2- subtypes; instead, ypN status was significantly related to DFS and OS. In HR+/HER2- subtype, both cN and ypN stages did not show significant survival differences, but the ypN number and the nodal response to NAC showed significant prognostic value (p < 0.05). Among HR-/HER2+ patients, all cN status, ypN status, ypN number, and nodal response were significantly associated with survival (p < 0.05). Furthermore, tumor biology, axillary surgery, ypN status, pathological tumor size, and radiotherapy were independent prognostic factors for DFS and OS. Conclusion: The ypN status after NAC provide more prognostic information than the initial cN stage in cN0-1 patients, and the surgical axillary staging after NAC may have high clinical value.

Evaluation of outcome of chemotherapy for breast cancer patients older than 70 years: A SEER-based study.

Background: With the aging of the population, the number of elderly breast cancer cases has increased. However, there is a lack of effective randomized clinical trial data to support whether elderly patients should receive chemotherapy. Our goal was to observe the relationship between chemotherapy and breast cancer-specific survival (BCSS) in elderly breast cancer patients and to identify those who could benefit from chemotherapy. Methods: We collected the data of patients who were diagnosed with invasive ductal carcinoma and older than 70 years in the SEER database from 1995 to 2016. The independent predictors of BCSS were identified by Cox regression analysis. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to eliminate confounding factors. Results: A total of 142,537 patients were collected, including 21,782 patients in the chemotherapy group and 120,755 patients in the non-chemotherapy group. We identified the same potential predictors of BCSS after PSM and IPTW, such as age, race, grade, stage, therapy, subtype. A nomogram for predicting 3-year, 5-year and 10-year BCSS was constructed. The 3-year, 5-year and 10-year AUCs of the nomogram were 0.842, 0.819, and 0.788. According to the risk stratification of model predictive scores, patients in the high-risk group achieved the greatest improvement in BCSS after receiving chemotherapy. Conclusions: Our study suggests that women older than 70 years with larger tumors, higher grade, positive nodes, negative hormone receptor and inactive local therapy gain prognostic benefits from chemotherapy, but for those with low- and median-risk, conventional chemotherapy should be administered cautiously.

A risk stratification model to predict chemotherapy benefit in medullary carcinoma of the breast: a population-based SEER database.

Whether patients with medullary breast carcinoma (MBC) receive chemotherapy is controversial. Therefore, the aim of our study was to screen out patients with MBC who benefit from chemotherapy. We enrolled 618 consecutive patients with MBC from The Surveillance, Epidemiology, and End Results (SEER) database (2010-2018). Cox regression analysis was used to identify independent prognostic factors. Next, a nomogram was constructed and evaluated using calibration plots and the area under the curve (AUC) of receiver operating characteristic (ROC) curves. Kaplan‒Meier curves were used to evaluate the overall survival (OS) benefit of chemotherapy in different risk groups. A total of 618 MBC patients were involved in our study, and an 8:2 ratio was used to randomly split them into a training cohort (n = 545) and a validation cohort (n = 136). Next, a nomogram predicting 3- and 5-year OS rates was constructed based on the five independent factors (age at diagnosis, T stage, N status, subtype and radiation). The nomogram AUCs for 3- and 5-year OS (training set: 0.793 and 0.797; validation set: 0.781 and 0.823) and calibration plots exhibited good discriminative and predictive ability. Additionally, a novel risk classification system for MBC patients demonstrated that we do not have enough evidence to support the benefit effect of chemotherapy for the high-risk group as the result is not statistically significant (total population: p = 0.180; training set: p = 0.340) but could improve OS in the low-risk group (total population: p = 0.001; training set: p = 0.001). Our results suggested that chemotherapy should be selected more carefully for high-risk groups based on a combination of factors and that the possibility of exemption from chemotherapy should be confirmed by more clinical trials in the future.

A Novel Risk-Scoring System to Identify the Potential Population Benefiting From Adjuvant Chemotherapy for Node-Negative TNBC Patients With Tumor Size Less Than 1 cm.

Background and Objectives: Whether chemotherapy is needed in node-negative triple-negative breast cancer (TNBC) patients with tumor size less than 1 cm is still controversial. In our research, we constructed a novel risk-scoring system to identify the potential TNBC patients benefiting from adjuvant chemotherapy in T1miN0M0, T1aN0M0, and T1bN0M0 stages. Methods: Relevant data were extracted from the SEER database. We applied Kaplan-Meier curves and the Cox hazards model for survival analysis and developed a nomogram of overall survival. The X-tile software was used for risk stratification. The information of TNBC patients treated in the First Affiliated Hospital of Xi'an Jiaotong University was used for the application of the model. Results: A total of 4266 patients who met the criteria of our study were included. T stage, age, race, surgery, and radiotherapy state were used to create the nomogram of overall survival. According to the total risk score, the patients were divided into high-risk (score g 73), median-risk (38 ≤ score < 73), and low-risk (score <38) groups. Chemotherapy can prolong the overall survival of patients in the median-risk and high-risk groups, while patients in the low-risk group can be exempted from chemotherapy. In addition, we also used the risk-scoring system in real-world patients as application and verification. Conclusion: We constructed a novel risk-scoring system that can be used as a chemotherapy decision-making tool for node-negative TNBC patients with tumor size less than 1 cm. Tumor size should not be the only criterion for chemotherapy treatment decision-making.

The prognostic significance of further axillary dissection for sentinel lymph node micrometastases in female breast cancer: A competing risk analysis using the SEER database.

Background: Sentinel lymph node (SLN) biopsy has been widely recognized as an excellent surgical and staging procedure for early-stage breast cancer, and its development has greatly improved the detection of micrometastases. However, the axillary treatment of micrometastasis has been the subject of much debate. Methods: We identified 427,131 women diagnosed with breast cancer from 2010 to 2018 in the Surveillance, Epidemiology, and End Results (SEER) database. Patients whose nodal status was micrometastases (pTxN1miM0) were classified into two groups: the SLNB only group and SLNB with complete ALND group, and we used these classifications to carry out propensity-score matching (PSM) analysis. The primary and secondary endpoints were OS and BCSS, respectively. We then implemented the Kaplan-Meier method and Cox proportional hazard model and used Fine and Gray competitive risk regression to identify factors associated with the risk of all-cause mortality. Results: After the PSM, 1,833 pairs were included in total. The SLNB with complete ALND showed no significant difference in OS (HR=1.04, 95% CI: 0.84-1.28, P=0.73) or BCSS (HR= 1.03, 95% CI: 0.79-1.35, P=0.82) compared to the SLNB only group, and axillary treatment was not associated with breast cancer-specific death (BCSD) (HR=1.13, 95% CI: 0.86-1.48, P=0.400) or other cause-specific death (OCSD) (HR=0.98, 95% CI:0.70-1.38, P=0.920). There was no statistically significant difference in the cumulative incidence of BCSD (Grey's test, P=0.819) or OCSD (Grey's test, P=0.788) for between the two groups either. For different molecular subtypes, patients in the SLNB only group showed no statistically significant differences from those in the SLNB with complete ALND group with Luminal A (HR=1.00, 95% CI:0.76-1.32, P=0.98) or Luminal B (HR=0.82, 95% CI:0.42-1.62, P=0.55) but similar OS to HER2-enriched (HR=1.58, 95% CI:0.81-3.07, P=0.19) or triple negative breast cancers (HR=1.18, 95% CI:0.76-1.81, P=0.46). Conclusions: Our results suggest that in early breast cancer patients with micrometastasis, complete ALND does not seem to be required and that SLNB suffices to control locoregional and distant disease, with no significant adverse effects on survival compared to complete ALND.

A nomogram to identify appropriate candidates for breast-conserving surgery among young women with breast cancer: A large cohort study.

Background: There is a gradual increase of female breast cancer under 35 years old, who was characterized as poor prognosis. Whether young patients could obtain greater survival benefits from breast-conserving surgery (BCS) than mastectomy remains controversial. Methods: Breast cancer patients (≤35 years old) were selected from the Surveillance, Epidemiology, and End Results (SEER) database and divided into BCS and mastectomy group. Propensity score matching (PSM) was used to eliminate the distributional imbalance of variables among two groups. The influence of BCS on overall survival (OS) and breast cancer-specific survival (BCSS) was evaluated by Cox regression. Logistic regression was used to identify factors related to the benefit of BCS and to construct a nomogram. The nomogram was validated by the First Affiliated Hospital of Xi'an Jiaotong University cohort. Results: Totally, 15,317 cases in the SEER database and 149 cases of external validation cohort were included. BCS was an independent protective factor for OS (P = 0.028) and BCSS (P = 0.042). A nomogram was established, and the AUC values both in the internal and external validation set were 0.780. The applicability of the model was verified in the PSM cohort and indicated that the survival advantage in the BCS-Benefit group was higher than that in the BCS-Nonbenefit and mastectomy group (P <0.001). Conclusions: For young breast cancer patients, BCS may bring better OS and BCSS than mastectomy, but not all benefit from it. We constructed a model for young patients (≤35 years old) that could identify appropriate candidates who benefit from BCS.

Identification of prognostic biomarkers among ICAMs in the breast cancer microenvironment.

BACKGROUND: Intercellular adhesion molecules (ICAMs) in the tumor microenvironment are closely related to immunity and affect the prognosis of cancer patients. OBJECTIVE: The aim of our study is to explore the correlation between ICAM expression, mutation, methylation and immunity and their prognostic value in breast cancer (BC) is not clear. METHODS: Online databases and tools such as UALCAN, COSMIC, cBioPortal, MethSurv, PrognoScan, Kaplan-Meier Plotter, GSCA and TIMER were utilized in this study. RESULTS: We found that the mRNA and protein expression levels of ICAM1 were upregulated in triple-negative breast cancer (TNBC) compared with normal tissues, and TNBC patients with high expression of ICAM1 had better overall survival (OS) and recurrence-free survival (RFS). The main types of ICAM1 gene variants were missense mutation and amplification, and ICAM1 showed a lower level of methylation in TNBC cancer tissues than in normal tissues, which was contrary to the high expression levels of ICAM1 mRNA and protein. Next, the function of ICAM1 was mainly related to the activation of apoptosis, epithelial-mesenchymal transition (EMT) and inhibition of the androgen receptor (AR) and estrogen receptor (ER) pathways. Meanwhile, functional pathway enrichment results showed that ICAM1 was also involved in the immune regulation process of BC. Furthermore, the expression of ICAM1 was positively associated with 6 types of tumor-infiltrating immune cells (CD8+ T cells, CD4+ T cells, B cells, neutrophils, macrophages and dendritic cells) and was also positively related to the expression of programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA4). CONCLUSIONS: Our research indicated that ICAM1 was likely to be a potential therapeutic target in TNBC.

Identification of necroptosis-related subtypes and prognosis model in triple negative breast cancer.

Background: Necroptosis is considered to be a new form of programmed necrotic cell death, which is associated with metastasis, progression and prognosis of various types of tumors. However, the potential role of necroptosis-related genes (NRGs) in the triple negative breast cancer (TNBC) is unclear. Methods: We extracted the gene expression and relevant clinicopathological data of TNBC from The Cancer Genome Atlas (TCGA) databases and the Gene Expression Omnibus (GEO) databases. We analyzed the expression, somatic mutation, and copy number variation (CNV) of 67 NRGs in TNBC, and then observed their interaction, biological functions, and prognosis value. By performing Lasso and COX regression analysis, a NRGs-related risk model for predicting overall survival (OS) was constructed and its predictive capabilities were verified. Finally, the relationship between risk_score and immune cell infiltration, tumor microenvironment (TME), immune checkpoint, and tumor mutation burden (TMB), cancer stem cell (CSC) index, and drug sensitivity were analyzed. Results: A total 67 NRGs were identified in our analysis. A small number of genes (23.81%) detected somatic mutation, most genes appeared to have a high frequency of CNV, and there was a close interaction between them. These genes were remarkably enriched in immune-related process. A seven-gene risk_score was generated, containing TPSG1, KRT6A, GPR19, EIF4EBP1, TLE1, SLC4A7, ESPN. The low-risk group has a better OS, higher immune score, TMB and CSC index, and lower IC50 value of common therapeutic agents in TNBC. To improve clinical practicability, we added age, stage_T and stage_N to the risk_score and construct a more comprehensive nomogram for predicting OS. It was verified that nomogram had good predictive capability, the AUC values for 1-, 3-, and 5-year OS were 0.847, 0.908, and 0.942. Conclusion: Our research identified the significant impact of NRGs on immunity and prognosis in TNBC. These findings were expected to provide a new strategy for personalize the treatment of TNBC and improve its clinical benefit.

A nomogram based on CENPP expression for survival prediction in breast cancer.

BACKGROUND: In recent years, it has been found that the expression of 17 centromere proteins (CENPs) was closely related to malignant tumors, however, the role of CENPs in breast cancer (BC) has not been fully investigated. This study intends to investigate the prognostic value of CENPs in BC and establish nomogram based on expression of CENPs to predict BC patients' prognosis. METHODS: A total of 800 BC patients with complete relevant data were included from the TCGA database and were further randomly divided into training set (N=480) and validation set (N=320). Univariate and multivariate Cox regression analysis were used to screen independent factors for overall survival (OS) prediction of BC patients in the training set. Then, the nomogram was established based on these independent predictors and further validated by receiver-operating characteristic (ROC) curves and calibration plots. The GEPIA and bcGenExMiner v4.4 databases were utilized to analyze mRNA expression of candidate gene in BC patients with different clinicopathological features, respectively. RESULTS: Multivariate Cox regression analysis showed that age, Her2 status, pathologic_T stage, pathologic_M stage and CENPP expression were of independent prognostic value for BC. CENPP was overexpressed in BC tissues (P<0.01) and lower expression of CENPP was associated with worse OS (P=0.005, HR =2.35; 95% CI: 1.30-4.23). We then established a nomogram based on those independent predictors, and the calibration curve demonstrated good fitness of the nomogram for OS prediction. In the training set, the AUCs of 3- and 5-year survival were 0.757 and 0.797, respectively. In the validation set, the AUCs of 3- and 5-year survival were 0.727 and 0.71, respectively. CONCLUSIONS: Our study showed that CENPP was a novel prognostic factor for patients with BC, and the established nomogram could provide valuable information on prognostic prediction for patients with BC.

Research on Effectiveness of Prior Cancer on Survival Outcomes for Patients with Nonmetastatic Triple-Negative Breast Cancer: A Competing Risk Analysis and Propensity Score Matching Analysis of the SEER Database.

INTRODUCTION: Knowledge of the effect of prior cancer on long-term survival outcomes for patients with nonmetastatic triple-negative breast cancer (TNBC) remained unclear. The aim of this study was to explore and identify the effectiveness of prior cancer on breast cancer-specific death (BCSD) and other cause-specific death (OCSD) in patients with nonmetastatic TNBC. MATERIALS AND METHODS: Data of 29,594 participants with nonmetastatic TNBC patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2016. Prognostic predictors were identified by propensity score matching (PSM) analysis combined with univariate cumulative incidence function (CIF) and multivariate Fine and Gray competitive risk analyses. RESULTS: Among the women with nonmetastatic TNBC included in the unmatched cohort, a total of 5,375 (18.2%) subjects had prior cancers (P-TNBC) and 24,219 (81.8%) had no prior cancer (NP-TNBC). Patients with P-TNBC tended to have poorer BCSD (Gray's test, p=0.0131) and OCSD (Gray's test, p=0.0009) in comparison with those with NP-TNBC after PSM. However, the risk of BCSD (p=0.291) and OCSD (p=0.084) found no difference among P-TNBC patients with one prior cancer and two or more prior cancers after PSM. Additionally, subjects with younger age, advanced T stage, advanced N stage, and advanced differentiation grade tumors were likely to develop BCSD, whereas those with breast-conserving surgery (BCS), radiotherapy, or chemotherapy tended to have a lower incidence of BCSD. CONCLUSION: Our study demonstrated that prior cancer was related to the worse BCSD and OCSD rate and could be identified as a reliable survival predictor for patients with nonmetastatic TNBC. This study may provide some reference value for the treatment mode of TNBC patients with prior cancer in the future.

A systematic analysis of a potential metabolism-related prognostic signature for breast cancer patients.

BACKGROUND: Metabolic pathways play an essential role in breast cancer. However, the role of metabolism-related genes in the early diagnosis of breast cancer remains unknown. METHODS: In our study, RNA sequencing (RNA-seq) expression data and clinicopathological information from The Cancer Genome Atlas (TCGA) and GSE20685 were obtained. Univariate cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed on the differentially expressed metabolism-related genes. Then, the formula of the metabolism-related risk model was composed, and the risk score of each patient was calculated. The breast cancer patients were divided into high-risk and low-risk groups with a cutoff of the median expression value of the risk score, and the prognostic analysis was also used to analyze the survival time between these two groups. In the end, we also analyzed the expression, interaction, and correlation among genes in the metabolism-related gene risk model. RESULTS: The results from the prognostic analysis indicated that the survival was significantly poorer in the high-risk group than in the low-risk group in both TCGA and GSE20685 datasets. In addition, after adjusting for different clinicopathological features in multivariate analysis, the metabolism-related risk model remained an independent prognostic indicator in TCGA dataset. CONCLUSIONS: In summary, we systematically developed a potential metabolism-related gene risk model for predicting prognosis in breast cancer patients.

A Competing Risk Analysis Model to Determine the Prognostic Value of Isolated Tumor Cells in Axillary Lymph Nodes for T1N0M0 Breast Cancer Patients Based on the Surveillance, Epidemiology, and End Results Database.

INTRODUCTION: Knowledge of the association between isolated tumor cells (ITCs) in breast cancer patients and the outcome is very limited. We aimed to determine the prognostic value of axillary lymph node ITCs for T1N0M0 female breast cancer (FBC) patients. METHODS: Data for T1N0M0 FBC patients staged ITCs negative [pN0(i-)] and positive [pN0(i+)] were extracted from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. Prognostic predictors were identified by Kaplan-Meier analysis, competing risk model, and Fine-Gray multivariable regression model. RESULTS: A total of 94,599 subjects were included, 88,632 of whom were staged at pN0(i-) and 5,967 were pN0(i+). Patients staged pN0(i+) had worse breast cancer-specific survival (BCSS) [hazard ratio (HR): 1.298, 95% CI = 1.069-1.576, P = 0.003] and higher breast cancer-specific death (BCSD) rate (Gray's test, P = 0.002) than pN0(i-) group. In the Fine-Gray multivariable regression analysis, the pN0(i+) group had higher BCSD rate (HR: 1.321, 95% CI = 1.109-1.575, P = 0.002) than pN0(i-) group. In subgroup analyses, no significant difference in BCSD was shown between the chemotherapy and non-chemotherapy subgroup (Gray's test, P = 0.069) or radiotherapy and non-radiotherapy subgroup (Gray's test, P = 0.096). CONCLUSION: ITC was independently related to the increase of the BCSD rate and could be identified as a reliable survival predictor for T1N0M0 FBC patients.

Research on the Role of Combined Chemotherapy and Radiotherapy in Patients With N+ Non-Metastatic Metaplastic Breast Carcinoma: A Competing Risk Analysis Model Based on the SEER database, 2000 to 2015.

PURPOSE: Due to the rarity of metaplastic breast carcinoma (MpBC), no randomized trials have investigated the role of combined chemotherapy and radiotherapy (CCRP) in this condition. We aimed to explore and identify the effectiveness of CCRP in patients with regional lymph node metastasis (N+) non-metastatic MpBC. MATERIALS AND METHODS: Data were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program database. We assessed the effects of CCRP on overall survival (OS), breast cancer-specific survival (BCSS), and breast cancer-specific death (BCSD) using Kaplan-Meier analysis, competing risk model analysis, and competing risk regression mode analysis. RESULTS: A total of 707 women and 361 death cases were included in the unmatched cohort, of which 76.45% (276/361) were BCSD, and 23.55% (85/361) were non-breast cancer-specific deaths (non-BCSD). Both the ChemT and CCRP groups had better OS (ChemT group: HR: 0.59, 95% CI: 0.45-0.78, P<0.001; CCRP group: HR: 0.31, 95% CI: 0.23-0.41, P<0.001) and BCSS (ChemT group: HR: 0.63, 95% CI: 0.45-0.87, P<0.001; CCRP group: HR: 0.32, 95%CI: 0.22-0.46, P<0.001) than the non-therapy group. Subjects in the CCRP group tended to have significantly lower cumulative BCSD (Gray's test, P=0.001) and non-BCSD (Gray's test, P<0.001) than the non-therapy group or ChemT group. In competing risk regression model analysis, subjects in the CCRP group had a better prognosis in BCSD (HR: 0.710, 95% CI: 0.508-0.993, P=0.045) rather than the ChemT group (HR: 1.081, 95% CI: 0.761-1.535, P=0.660) than the non-therapy group. CONCLUSION: Our study demonstrated that CCRP could significantly decrease the risk of death for both BCSD and non-BCSD and provided a valid therapeutic strategy for patients with N+ non-metastatic MpBC.