Predicting the risk of axillary lymph node metastasis in early breast cancer patients based on ultrasonographic-clinicopathologic features and the use of nomograms: a prospective single-center observational study.

OBJECTIVES: The purpose of this study was to establish two preoperative nomograms to evaluate the risk for axillary lymph node (ALN) metastasis in early breast cancer patients based on ultrasonographic-clinicopathologic features. METHODS: We prospectively evaluated 593 consecutive female participants who were diagnosed with cT1-3N0-1M0 breast cancer between March 2018 and May 2019 at Sun Yat-Sen Memorial Hospital. The participants were randomly classified into training and validation sets in a 4:1 ratio for the development and validation of the nomograms, respectively. Multivariate logistic regression analysis was performed to identify independent predictors of ALN status. We developed Nomogram A and Nomogram B to predict ALN metastasis (presence vs. absence) and the number of metastatic ALNs (≤ 2 vs. > 2), respectively. RESULTS: A total of 528 participants were evaluated in the final analyses. Multivariable analysis revealed that the number of suspicious lymph nodes, long axis, short-to-long axis ratio, cortical thickness, tumor location, and histological grade were independent predictors of ALN status. The AUCs of nomogram A in the training and validation groups were 0.83 and 0.78, respectively. The AUCs of nomogram B in the training and validation groups were 0.87 and 0.87, respectively. Both nomograms were well-calibrated. CONCLUSION: We developed two preoperative nomograms that can be used to predict ALN metastasis (presence vs. absence) and the number of metastatic ALNs (≤ 2 vs. > 2) in early breast cancer patients. Both nomograms are useful tools that will help clinicians predict the risk of ALN metastasis and facilitate therapy decision-making about axillary surgery. KEY POINTS: • We developed two preoperative nomograms to predict axillary lymph node status based on ultrasonographic-clinicopathologic features. • Nomogram A was used to predict axillary lymph node metastasis (presence vs. absence). The AUCs in the training and validation groups were 0.83 and 0.78, respectively. Nomogram B was used to estimate the number of metastatic lymph nodes ( ≤ 2 vs. > 2). The AUCs in the training and validation group were 0.87 and 0.87, respectively. • Our nomograms may help clinicians weigh the risks and benefits of axillary surgery more appropriately.

Akt pathway activation reduces platelet apoptosis and contributes to the increase of platelet counts in solid tumor patients.

Platelets counts increase in various cancer patients, which is associated with poor prognosis. However, the cause of high platelet counts in cancer patients is still not fully understood. Here we demonstrated that compared with healthy controls, there were significant differences in platelet parameters, mean platelet volume (MPV), platelet distribution width (PDW), platelet larger cell ratio (P-LCR), and platelet crit (PCT), reflecting platelet volume in breast cancer patients by clinical retrospective analysis. The mitochondrial transmembrane potential (ΔΨm) depolarization and phosphatidylserine (PS) externalization declined, accompanied by reduced expression of pro-apoptotic factors Bak, Bax and apoptotic executor caspase-3, and elevated of anti-apoptotic factor Bcl-xl in various cancer patients' platelets. Notably, the phosphorylation level of Akt and its downstream target Bad increased in platelets from cancer patients. MK2206, the inhibitor of Akt, reduced the phosphorylation level of Akt and Bad, and induced apoptosis of platelets. When platelets from healthy controls cocultured with the cultural supernatant of cancer cells, the phosphorylation level of Akt and Bad in the platelets was elevated and the cultural supernatant of cancer cells could rescue the apoptosis of platelet induced by MK2206. Therefore, in our study the apoptosis of platelets in cancer patients was declined, which exerted an influence on the rise of platelet counts in breast cancer patients. The cross-talking between tumor and platelets could affect platelet apoptosis by regulating Akt signaling pathway in platelets.

Association study of a genetic variant in the long intergenic noncoding RNA (linc01080) with schizophrenia in Han Chinese.

BACKGROUND: Schizophrenia is currently considered to be a polygene-related disease with unknown etiology. This research will verify whether the single nucleotide polymorphism (SNP) of the long intergenic noncoding RNA01080 (linc01080) contributes to the susceptibility and phenotypic heterogeneity of schizophrenia, with a view to providing data support for the prevention and individualized treatment of this disease. METHOD: The SNP rs7990916 in linc01080 were genotyped in 1139 schizophrenic and 1039 controls in a Southern Chinese Han population by the improved multiplex ligation detection reaction (imLDR) technique. Meanwhile, we assessed and analyzed the association between this SNP and schizophrenics' clinical symptoms, and the cognitive function. RESULT: There was no significant difference in genotype distribution, allele frequency distribution, gender stratification analysis between the two groups. However, the SNP of rs7990916 was significantly associated with the age of onset in patients with schizophrenia (P = 8.22E-07), patients with T allele had earlier onset age compared with CC genotype carriers. In terms of cognitive function, patients with T allele scored lower than CC genotype carriers in the Tower of London score and symbol coding score in the Brief assessment of Cognition (BACS), and the difference was statistically significant (P = 0.014, P = 0.022, respectively). CONCLUSION: Our data show for the first time that linc01080 polymorphism may affect the age of onset and neurocognitive function in patients with schizophrenia.

Nomograms for prediction of overall and cancer-specific survival in young breast cancer.

PURPOSE: To assess the prognostic risk factors and establish prognostic nomograms based on lymph node ratio (LNR) to predict the survival of young patients with breast cancer (BC). METHODS: Patients aged < 40 years and diagnosed with BC between 2010 and 2016 from the Surveillance, Epidemiology and End Results database were assessed. Nomograms incorporating LNR were constructed to predict overall survival (OS) and breast cancer-specific survival (BCSS) based on Cox proportional hazards model. The performance of the nomograms was assessed by C-index, calibration curves, receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and risk group stratification and compared with the TNM staging system. RESULTS: Based on the univariate and multivariate Cox regression analysis, significant prognostic factors were identified and integrated to create the nomograms for OS and BCSS. The calibration curves indicated optimal agreement between model predictions and actual observations. The nomograms showed favorable sensitivity with a C-index of 0.8351 (95% CI 0.8234-0.8469) for OS and 0.8474 (95% CI 0.8355-0.8594) for BCSS. The ROC curves of the nomograms showed better predictive ability than those of the TNM staging system for OS (AUC: 0.8503 vs. 0.7819) and BSCC (AUC: 0.8607 vs. 0.8081). Significant differences in Kaplan-Meier curves were observed in patients stratified into different risk groups (p < 0.001). CONCLUSIONS: These nomograms provided more accurate individualized risk prediction of OS and BCSS and may assist clinicians in making decisions for young patients with BC.

[Effect of baicalin on signal transduction and activating transcription factor expression in ulcerative colitis patients].

OBJECTIVE: To explore the intervention of baicalin on signal transduction and activating transcription factor expression of ulcerative colitis (UC) patients. METHODS: Recruited were UC patients at Outpatient Department of Digestive Disease, Inpatient Department of Digestive Disease, Center for Digestive Endoscopy of College City Branch, Guangdong Provincial Hospital of Traditional Chinese Medicine, and Southern Hospital affiliated to Southern Medical University from June 2010 to January 2011. They were assigned to the UC group (33 cases) and the diarrhea-predominant irritable bowel syndrome (IBS-D) group (30 cases). Another 30 healthy subjects were recruited as a healthy control group. Peripheral blood mononuclear cells (PBMCs) in vitro intervened by different concentrations baicalin were taken from UC patients. IL23R gene expressions in vitro intervened by different concentrations baicalin were detected using Q-PCR. Expressions of signal transducer and activator of transcription 4 (STAT4) , STAT6, phosphorylated-STAT4 (p-STAT4), and p-STAT6 were detected using Western blot. Serum levels of IFN-γ, IL-4, IL-6, and IL-10 were measured by ELISA. Effects of different concentrations baicalin on expressions of PBMCs, and levels of IFN-γ, IL-4, IL-10 of UC patients were also detected. RESULTS: Compared with the negative control group, 40 µmol baicalin obviously decreased IL23R gene expression of UC patients (P <0. 01). Compared with the healthy control group and the IBS-D group, p-STAT4/STAT4 ratios increased, p-STAT6/STAT6 ratios decreased, levels of IFN-γ, IL-4, IL-10 all increased in the US group (all P <0. 05). Compared with the negative control, 5 and 10 µmol baicalin groups, 20 and 40 moL baicalin obviously decreased p-STAT4/STAT4 ratios (all P <0. 05); 20 and 40 µmoL baicalin obviously increased p-STAT6/STAT6 ratios (all P <0. 05); 20 and 40 µmoL baicalin obviously lowered levels of IFN-γ and IL-4, and elevated IL-10 levels (all P <0. 05). CONCLUSION: 40 µmoL baicalin could in vitro inhibit p-STAT4/STAT4 ratios, adjust p-STAT6/STAT6 ratios and related cytokines, thereby balancing the immunity and relieving inflammatory reactions of UC.

The overexpression of hypomethylated miR-663 induces chemotherapy resistance in human breast cancer cells by targeting heparin sulfate proteoglycan 2 (HSPG2).

MicroRNAs are involved in regulating the biology of cancer cells, but their involvement in chemoresistance is not fully understood. We found that miR-663 was up-regulated in our induced multidrug-resistant MDA-MB-231/ADM cell line and that this up-regulation was closely related to chemosensitivity. In the present study, we aimed to clarify the role of miR-663 in regulating the chemoresistance of breast cancer. MicroRNA microarray and quantitative RT-PCR assays were used to identify differentially expressed microRNAs. Cell apoptosis was evaluated by annexin V/propidium iodide staining, TUNEL, and reactive oxygen species generation analysis. The expression of miR-663 and HSPG2 in breast cancer tissues was detected by in situ hybridization and immunohistochemistry. The potential targets of miR-663 were defined by a luciferase reporter assay. Bisulfite sequencing PCR was used to analyze the methylation status. We found that miR-663 was significantly elevated in MDA-MB-231/ADM cells, and the down-regulation of miR-663 sensitized MDA-MB-231/ADM cells to both cyclophosphamide and docetaxel. The overexpression of miR-663 in breast tumor tissues was associated with chemoresistance; in MDA-MB-231 cells, this chemoresistance was accompanied by the down-regulation of HSPG2, which was identified as a target of miR-663. MDA-MB-231/ADM contained fewer methylated CpG sites than its parental cell line, and miR-663 expression in MDA-MB-231 cells was reactivated by 5-aza-29-deoxycytidine treatment, indicating that DNA methylation may play a functional role in the expression of miR-663. Our findings suggest that the overexpression of hypomethylated miR-663 induced chemoresistance in breast cancer cells by down-regulating HSPG2, thus providing a potential target for the development of an microRNA-based approach for breast cancer therapy.

Pyk2 and Src mediate signaling to CCL18-induced breast cancer metastasis.

Pyk2 and Src phosphorylation is initiated by CCL18, which promotes breast cancer metastasis via its functional G protein-coupled receptor PITPNM3. However, the function of Pyk2 and Src in CCL18-induced breast cancer metastasis is poorly understood. Quantitative reverse-transcription polymerase chain reactions (qRT-PCRs), Western blot, boyden chamber assay, and adherence assay were performed to delineate the consequences of Pyk2/Src in CCL18-induced breast cancer cells. Co-immunoprecipitation and immunofluorescence were performed to analyze the interaction of proteins. Upon the binding of CCL18 to PITPNM3, Pyk2 translocates from the cytoplasm to the plasma membrane to form a stable complex with PITPNM3, subsequently activating Src kinase. Moreover, upon stimulation with CCL18, Pyk2 and Src become essential for integrin alpha5/beta1 clustering-dependent adherence, migration, and invasion. Pyk2 and Src are important in CCL18-induced breast cancer metastasis.

PKCα Induced the Generation of Extracellular Vesicles in Activated Platelets to Promote Breast Cancer Metastasis.

Platelet extracellular vesicles (PEVs) play an important role in tumor development. However, the mechanisms underlying their biogenesis have not been fully elucidated. Protein kinase Cα (PKCα) is an important regulator of platelet activation, but the effect of PKCα on EV generation is unclear. We used small-particle flow cytometry and found that the number of PEVs was increased in patients with breast cancer compared to those with benign breast disease. This was accompanied by increased levels of activated PKCα in breast cancer platelets. Treating platelets with the PKCα agonist phorbol 12-myristate 13-acetate (PMA) increased the phosphorylation PKCα and induced PEV production, while the PKCα inhibitor GÖ6976 showed the opposite effects. Notably, incubating platelets from patients with benign tumors with the culture supernatant of MDA-MB-231 cells induced PKCα phosphorylation in the platelets. Mass spectrometry and coimmunoprecipitation assays showed that Dynamin 2 (DNM2), a member of the guanosine-triphosphate-binding protein family, might cooperate with activated PKCα to regulate PEV production by breast cancer platelets. Similar results were observed in a mouse model of lung metastasis. In addition, PEVs were engulfed by breast cancer cells and promoted cancer cell migration and invasion via miR-1297 delivery. These findings suggested that PKCα cooperates with DNM2 to induce PEV generation, and PEV release might triggered by factors in the breast cancer environment.

A single-building damage detection model based on multi-feature fusion: A case study in Yangbi.

Accurate and effective identification, determination of the location, and classification of damaged buildings are essential after destructive earthquakes. However, the accuracy of image change detection is limited because of the many texture features and changes in non-building information. In this context, a model for single-building damage detection based on multi-feature fusion is proposed. First, the normalized Digital Surface Model (nDSM) was extracted from the DSM through iterative filtering and point cloud thinning, followed by the extraction of building contour information. Next, single-building images were generated from different data sources through the region of interest (ROI), and the optimal texture feature parameters were extracted for fusion. Afterward, principal-component analysis (PCA) was conducted to suppress multi-feature correlation-induced information redundancy. Finally, the damage to buildings was quantitatively evaluated, and the model was compared with 13 models. The results confirmed the practicability of the model for the Yangbi MS6.4 and Honghe MS5.0 earthquakes.

MicroRNA 34c gene down-regulation via DNA methylation promotes self-renewal and epithelial-mesenchymal transition in breast tumor-initiating cells.

Tumor-initiating cells (T-ICs), a subpopulation of cancer cells with stem cell-like properties, are related to tumor relapse and metastasis. Our previous studies identified a distinct profile of microRNA (miRNA) expression in breast T-ICs (BT-ICs), and the dysregulated miRNAs contribute to the self-renewal and tumorigenesis of these cells. However, the underlying mechanisms for miRNA dysregulation in BT-ICs remain obscure. In the present study, we demonstrated that the expression and function of miR-34c were reduced in the BT-ICs of MCF-7 and SK-3rd cells, a breast cancer cell line enriched for BT-ICs. Ectopic expression of miR-34c reduced the self-renewal of BT-ICs, inhibited epithelial-mesenchymal transition, and suppressed migration of the tumor cells via silencing target gene Notch4. Furthermore, we identified a single hypermethylated CpG site in the promoter region of miR-34c gene that contributed to transcriptional repression of miR-34c in BT-ICs by reducing DNA binding activities of Sp1. Therefore, miR-34c reduction in BT-ICs induced by a single hypermethylated CpG site in the promoter region promotes self-renewal and epithelial-mesenchymal transition of BT-ICs.

Effect of 50-Hertz Sinusoidal Vibration on the Uterus in Ovariectomy-Induced Osteoporotic Rats.

Objective: To evaluate the influence of sinusoidal vibration (50-Hertz) stimulation on the uterus of osteoporotic rats. Methods: We constructed an osteoporosis rat model by ovariectomy (OVX). 36 3-month-old Sprague Dawley rats were randomly divided into the control group, vibrating group, sham operation group, sham operation vibrating group, OVX group, and OVX vibrating group (n = 6 per group). Rats started to vibrate one week after the operation: one 10 minutes 50-Hertz sinusoidal vibration per day, except for Saturday and Sunday. In the second, 8, and 12 week after vibration stimulation, rats were sacrificed in batches. And then, the uteruses were taken out to measure the wet weight and calculate uterus relative wet weight. Results: Compared with the control group, OVA induced a significant increase in wet weight and relative wet weight in rat uterus. The vibration was to the uterus wet weight and the uterus relative wet weight in ovariectomized rats and at the same time had no significant effect, but the 12-week prolonged vibration can significantly reduce the uterus wet weight and the uterus relative wet weight in ovariectomized rats than 2 weeks. Conclusions: The uterus wet weight and the uterus relative wet weight were increased in the OVA-induced osteoporosis rats. The 50-Hertz sinusoidal vibration had no significant effect on the uterus wet weight and the uterus relative wet weight in the ovariectomized rats at the same time, but 12 weeks of vibration can significantly reduce the uterine wet weight and uterine relative wet weight of ovariectomized rats. And the uterus relative wet weight can be used as a new indicator of stimulating the uterus.

Plasma miR-221 as a predictive biomarker for chemoresistance in breast cancer patients who previously received neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly being used in breast cancer treatment. Research has revealed an elevated expression of miR-221 in adriamycinresistant MCF-7/ADR cells. This study aimed to explore the potential role of miR-221 as a biomarker for chemosensitivity in breast cancer patients who previously received NAC. PATIENTS AND METHODS: The expression levels of circulating miR-221 in the plasma of 93 breast cancer patients who previously received NAC and in 32 healthy individuals were assessed. The correlations between miR-221 and clinicopathological features and chemosensitivity were also analysed. RESULTS: The expression level of miR-221 was significantly associated with hormone receptor (HR) status (p = 0.008). Patients with higher plasma miR-221 levels tended to be HR-negative. Patients with different miR-221 levels had significant differences in the overall response rate (p = 0.044) but not in the pathologic complete response rate (p = 0.477). CONCLUSION: Our results indicate that plasma miR-221 may be a predictive biomarker for sensitivity to NAC in breast cancer patients.

miR-124 suppresses multiple steps of breast cancer metastasis by targeting a cohort of pro-metastatic genes in vitro.

Metastasis is a multistep process involving modification of morphology to suit migration, reduction of tumor cell adhesion to the extracellular matrix, increase of cell mobility, tumor cell resistance to anoikis, and other steps. MicroRNAs are well-suited to regulate tumor metastasis due to their capacity to repress numerous target genes in a coordinated manner, thereby enabling their intervention at multiple steps of the invasion-metastasis cascade. In this study, we identified a microRNA exemplifying these attributes, miR-124, whose expression was reduced in aggressive MDA-MB-231 and SK-3rd breast cancer cells. Down-regulation of miR-124 expression in highly aggressive breast cancer cells contributed in part to DNA hypermethylation around the promoters of the three genes encoding miR-124. Ectopic expression of miR-124 in MDA-MB-231 cells suppressed metastasis-related traits including formation of spindle-like morphology, migratory capacity, adhesion to fibronectin, and anoikis. These findings indicate that miR-124 suppresses multiple steps of metastasis by diverse mechanisms in breast cancer cells and suggest a potential application of miR-124 in breast cancer treatment.

Shaoyao Decoction Inhibits Inflammation and Improves Intestinal Barrier Function in Mice With Dextran Sulfate Sodium-Induced Colitis.

Shaoyao decoction (SYD), a classical traditional Chinese medicine formula, is effective for the treatment of inflammatory bowel disease (IBD). This study was designed to investigate the therapeutic effects of SYD on IBD and possible mechanisms. Dextran sulfate sodium (DSS, 3.5%) was used to induce colitis in C57BL/6 mice. Disease phenotypes were investigated based on disease activity index (DAI), colon length, and microscopic and macroscopic scores. Additionally, the presence of proinflammatory cytokines, immune cell infiltrates, intestinal cell proliferation, apoptosis, epithelial permeability, signal transducer and activator of transcription 3 (STAT3), and nuclear factor-κB (NF-κB) signaling, as well as the intestinal mucosal barrier function, were investigated. The administration of SYD significantly ameliorated the clinical signs, suppressed the levels of proinflammatory cytokines, and reduced immune cell infiltrates into colonic tissues of DSS-induced colitis model mice. SYD also significantly reduced the DSS-induced activation of STAT3 and NF-κB signaling. Furthermore, SYD promoted epithelial integrity by regulating epithelial cell apoptosis and epithelial permeability. Finally, we demonstrated that SYD protected the intestinal barrier function by significantly regulating the mucus layer genes Muc1, Muc2, Muc4, and Tff3, as well as the epithelial barrier genes Z O -1 and Occludin. Our results indicate that SYD has a protective effect on DSS-induced colitis, which is attributable to its anti-inflammatory activity and intestinal barrier function-enhancing effects. These results provide valuable insights into the pharmacological actions of SYD for the treatment of IBD.

Establishment and Validation of a Preoperative MRI-based Nomogram for Predicting the Risk of Malignancy in Patients with Breast Tumor.

Purpose: To establish a preoperative nomogram incorporating morphological and dynamic contrast-enhanced (DCE) features to individually predict the risk of malignancy in patients with breast tumor. Methods A total of 447 consecutive female patients who were divided into the primary cohort (n=326) and the validation cohort (n=121) were enrolled between March 2015 to January 2018. Univariate and multivariate logistic regression analyses were used to identify the potential independent indicators of malignancy. An MRI-based nomogram integrating morphological features and kinetic curves was developed to achieve individualized risk prediction of malignancy in patients with breast masses. The discrimination, calibration ability and clinical utility of the MRI-based model were assessed using C-index, calibration curve and decision curve analysis. Results: Age, tumor size, margin, internal enhancement characteristics, and kinetic curve were confirmed as the independent predictors of malignancy. The AUC of MRI-based nomogram was 0.940 (95% CI: 0.911-0.970) and 0.894 (95% CI: 0.816-0.974) in the primary cohort and validation cohort, respectively. 447 patients were subdivided into the low-risk group (n=107) and high-risk group (n=340) based on the optimal cut-off value of 21.704. The high-risk patients had a higher likelihood of harboring malignancy. Conclusion: The MRI-based nomogram can be used to achieve an accurate individualized risk prediction of malignancy and reduce unnecessary breast biopsy.

Characterization of long non-coding RNA and messenger RNA profiles in laryngeal cancer by weighted gene co-expression network analysis.

Laryngeal cancer (LC) is a malignant tumor in the head and neck region. It was recently elucidated that long non-coding RNAs (lncRNAs) participate in the pathogenesis of LC. However, the detailed mechanism of lncRNA in LC and whether long non-coding RNAs serve as effective biomarkers remains unclear. Ribonucleic acid (RNA) sequence data of LC and 11 patient clinical traits were extracted from The Cancer Genome Atlas (TCGA) database and analyzed by weighted gene co-expression network analysis (WGCNA). A total of 9 co-expression modules were identified. The co-expression Pink module significantly correlated with four clinical traits, including history of smoking, lymph node count, tumor status, and the success of follow-up treatment. Based on the co-expression Pink module, lncRNA-microRNA (miRNA)-messenger RNA (mRNA) and lncRNA-RNA binding protein-mRNA networks were constructed. We found that 8 lncRNAs significantly impacted overall survival (OS) in LC patients. These identified lncRNA and hub gene biomarkers were also validated in multiple LC cells in vitro via qPCR. Taken together, this study provided the framework of co-expression gene modules of LC and identified some important biomarkers in LC development and disease progression.

Does establishing a preoperative nomogram including ultrasonographic findings help predict the likelihood of malignancy in patients with microcalcifications?

BACKGROUND: Mammography (MG) is highly sensitive for detecting microcalcifications, but has low specificity. This study investigates whether establishing a preoperative nomogram including ultrasonographic findings can help predict the likelihood of malignancy in patients with mammographic microcalcification. METHODS: Between May 2012 and January 2017, 475 patients with suspicious microcalcifications detected on MG underwent ultrasonography (US). The χ2 test was used to screen risk factors among the variables. Then, a multivariate logistic regression analysis was performed to identify independent predictors of malignant microcalcifications. A mammographic nomogram (M nomogram) and mammographic-ultrasonographic nomogram (M-U nomogram) were established based on multivariate logistic regression models. The discriminatory ability and clinical utility of both nomograms were compared by the receiver operating characteristics curve and decision curve analysis. The calibration ability was evaluated using a calibration curve. RESULTS: Among the cases, 68.2% (324/475) were pathologically diagnosed as breast cancer and 31.8% (151/475) were benign lesions. Based on multivariate logistic regression analysis, age, clinical manifestation, morphology and distribution of microcalcifications on MG and lesions associated with microcalcifications on US were confirmed as independent predictors of malignant microcalcifications. In terms of discrimination ability, the C-index of the M-U nomogram was significantly higher than that of the M nomogram (0.917 vs 0.897, p = 0.006). The bias-corrected curve was close to the ideal line in the calibration curve. Decision curve analysis suggested that the M-U nomogram was superior to M nomogram. CONCLUSIONS: Combining mammographic parameters with ultrasonographic findings in a nomogram provided better performance than an M nomogram alone, especially for dense breasts, which suggests the value of ultrasonographic finding for individualized prediction of malignancy in patients with microcalcifications.

Combined Let-7a and H19 Signature: A Prognostic Index of Progression-Free Survival in Primary Breast Cancer Patients.

PURPOSE: The long non-coding RNA H19, a conservatively imprinted gene, acts as a molecular sponge for the let-7 family, which has been identified as a set of tumor suppressors. However, the combined prognostic value of H19 and let-7a signature in breast cancer patients remains unclear. METHODS: In this research we assessed the prognostic value of the combined H19 and let-7a signature in breast cancer patients by retrospectively reviewing that data of 79 patients who underwent neoadjuvant chemotherapy; we also investigated the expression and function of H19 in breast cancer cell lines in vitro. Survival data were calculated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate survival analyses were conducted using the Cox proportional hazards regression method. As determined using X-tile, the optimal cutoff value for the risk score to assess progression-free survival (PFS) based on the combined signature was -0.1. RESULTS: Patients with an overall positive treatment response had higher let-7a and lower H19 levels. In addition, let-7a expression was negatively correlated with H19 expression. Patients with a risk score of >-0.1 had shorter overall survival and PFS. In vitro data showed that chemoresistant cell lines exhibit higher H19 and lower let-7a levels and knockdown H19 restores paclitaxel sensitivity. CONCLUSION: Our results suggest that the combined let-7a and H19 signature is a novel prognostic factor for breast cancer patients treated with neoadjuvant chemotherapy.

Factors associated with the increasing trend of contralateral prophylactic mastectomy among patients with ductal carcinoma in situ: Analysis of Surveillance, Epidemiology, and End Results data.

PURPOSE: Our study aimed to investigate the factors influencing trends of contralateral prophylactic mastectomy (CPM) among patients with unilateral ductal carcinoma in situ (DCIS). PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) data to identify patients with unilateral DCIS diagnosed from 1998 to 2013. Patients were categorized as breast-conserving surgery (BCS), Unilateral Mastectomy and CPM group. Univariate and multivariate logistic regressions were applied to assess the factors associated with undergoing CPM among mastectomy patients. The trends of CPM among mastectomy patients through year were presented by different subgroups of sociodemographic and pathological characteristics. RESULTS: Of those, 105326 patients with DCIS were identified, and 6370 patients underwent CPM. The proportion of CPM was 6.05% for all surgically-treated patients and 21.09% for mastectomy patients, and it increased more than six-fold between 1998 and 2013 (from 1.74% to 10.89% for all surgically-treated patients and from 5.44% to 37.47% for mastectomy patients). Younger age, white race, married status, smaller tumor size, positive ER and PR status were significantly associated with higher CPM proportion among mastectomy patients. The proportion of CPM was increasing through year, and the increasing trends were obvious in the subgroups of younger, white, married, metropolitan, with higher bachelor degree and higher median family income patients, while there were no apparent differences in the trends between subgroups of pathological characteristics. CONCLUSION: The trends of CPM among mastectomy patients were increasing through years and influenced by patients' sociodemographic characteristics, but not pathological characteristics.