Search

Purpose: To comparing the survival in different strategies, preoperative systemic treatment (PST) versus upfront surgery (US) in patients of HER2-positive early breast cancer in real-world.Methods: Eligible patients from 2012 to 2015 were classified as PST or US group prospectively, according to the real upfront treatment. The primary endpoint is disease-free survival (DFS), the second endpoint is overall survival (OS). All the outcomes were examined in unadjusted model, propensity score matching (PSM) model, and inverse probability of treatment weighting (IPTW) model. Results: Finally, 1067 eligible patients (215 in PST group, 852 in US group) were included into analysis (Table 1). In unweighted analysis, the cumulative DFS of PST group was significantly lower than US group (78.1% vs 87.7%, P *Proportions and medians are weighted using IPTW, all covariates included in the propensity analysis. Abbreviations: PSM, propensity score matching, IPTW, inverse probability of treatment weighting, PST, preoperative systemic treatment, US, upfront surgery, SMD, standardized mean difference, ER, estrogen receptor, PR, progesterone receptor.In IPTW model, the DFS rate of the PST group was 81.3% versus 80.8% of the US group, and the OS rate of the PST group was 92.1% versus 90.3% (Figure 2E, 2F), both having no significantly differences (Table 4). In further stratified analysis (Figure 3E, 3F), as in PSM model, the DFS and OS rate of the patients without pCR after PST (73.1%, 88.4%) were worse than those with pCR (96.6%, 99.3%) and US group (80.8%, 90.3%), respectively. Table 1. The clinicopathologic characteristics of two groups in PSM and IPTW modelsCharacteristicsNumber of casesUnweighted primary samplePSM modelIPTW model*PST group (215)US group (852)SMDPST group (145)US group (145)SMDPST group (765)US group (1021)SMDN (%)N (%)N (%)N (%)N (%)N (%)Age (years, medium, 95%CI)50, 39~6150, 33~640.0550, 40~6549, 34~620.1049, 39~6750, 31~640.03Stage T14588 (3.7)450 (52.8)0.7018(3.7)10 (6.9)0.03280 (10.5)450 (44.1)0.4672529157 (73.0)372 (43.7)118 (81.4)116 (80.0)635 (83.0)458 (44.9)38050 (23.3)30 (3.5)19 (13.1)19 (13.1)50 (6.5)113 (11.1)Stage N057137 (17.2)534 (62.7)1.04837 (17.2)32 (22.1)0.081310 (40.5)538 (52.7)0.2461596178 (82.8)318 (37.3)108 (81.4)113 (77.9)455 (59.5)483 (47.3)Grade1 and 252292 (42.8)430 (50.5)0.15477 (53.1)89 (61.4)0.168345 (45.1)493 (48.3)0.0643545123 (57.2)422 (49.5)68 (46.9)56 (38.6)420 (54.9)528 (51.7)ERNegative536142 (66.0)394 (46.2)0.40787 (60.0)68 (46.9)0.265386 (50.5)513 (50.2)0.004Positive53173 (34.0)458 (53.8)58 (40.0)77 (53.1)379 (49.5)508 (49.8)PRNegative649171 (79.5)478 (56.1)0.418108 (74.5)113 (77.9)0.081499 (65.2)625 (61.2)0.083Positive41844 (20.5)374 (43.9)37 (25.5)32 (22.1)266 (34.8)396 (38.8) Citation Format: Yang Hongjian, Xingfei Yu, Chen Wang, Zheng Yabing, Hu Jiejie, Xiying Shao, Liming Sheng, Juan Lin, Yuqin Ding, Haojun Xuan, Lijie Gong, Weiliang Feng, Chengdong Qin, Daobao Chen, Yang Yu. Preoperative systemic therapy versus upfront surgery in HER2-positive early breast cancer: A prospective nested case-control study in the real world [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-52.

A thermoelectric-hydraulic numerical model is built for thermoelectric recuperators with wavy and straight fins under large longitudinal temperature difference, and their performance is analyzed. It is found that the comprehensive performance of the wavy-fin thermoelectric recuperator is better than that of straight-fin thermoelectric recuperator. The maximum output powers of the two thermoelectric recuperators are 0.251 mW and 0.236 mW at inlet velocity of 1.7 m � s-1. When the ratio of wave height to wave length is 0.1, the maximum output power is 0.251 mW and output power per unit volume is 414.8 W � m-3. Taguchi method is used to optimize the wavy-fin thermoelectric recuperator. It is found that reducing channel width and plate thickness is beneficial to increase the output power and output power per unit volume for the wavy-fin thermoelectric recuperator. Increasing fin height and fin thickness is beneficial to the output power, but disadvantage to the output power per unit volume.

Background Triple-negative breast cancer (TNBC) is characterized by its aggressiveness and poor prognosis. Docetaxel is the common chemotherapeutic drug used in the treatment of TNBC. However, resistance to docetaxel has limited the effectiveness of TNBC treatment. Petroleum ether extracts of Curcuma zedoaria (PECZ) can inhibit the proliferation of MDA-MB-231 cells. However, the effect of PECZ on docetaxel resistance is not clear. Methods A docetaxel-resistant MDA-MB-231 (MDA-MB-231/docetaxel) cell line was established, and Cell Counting Kit-8 (CCK-8), quantitative real-time PCR (qRT-PCR), and western blotting assays were used to evaluate the effect of docetaxel resistance in MDA-MB-231 cells. Next, CCK-8 was also performed to detect the effect of docetaxel or the combination treatment of docetaxel and PECZ on the proliferation of MDA-MB-231/docetaxel cells. Thereafter, MDA-MB-231/docetaxel cells were subcutaneously injected into nude mice to induce a TNBC xenograft model, and the mice were divided into a model group, docetaxel group, PECZ group, and combination of docetaxel and PECZ group. Subsequently, hematoxylin and eosin (HE) staining, immunohistochemical, qRT-PCR, and western blotting were used to estimate the effect of pre-treatment with PECZ on docetaxel tolerance reversal. Results PECZ significantly inhibited the expression of pregnane X receptor (PXR), multidrug resistance 1 (MDR1), breast cancer resistance protein (BCRP), and cytochrome P-450 (CYP3A4) in MDA-MB-231/docetaxel cells. Only higher concentrations of docetaxel could inhibit the viability of MDA-MB-231/docetaxel cells. When pre-treated with PECZ, lower concentrations of docetaxel could significantly inhibit cell viability. Meanwhile, combination treatment also reduced the tumor volume, ameliorated the pathological change of tumor tissues, and down-regulated the expressions of PXR, MDR1, BCRP, and CYP3A4 (according to HE staining, immunohistochemical, qRT-PCR and western blotting results in vivo). Conclusions Our research showed that PECZ reversed docetaxel resistance in TNBC by PXR both in vitro and in vivo, which provides the basis for further investigations into the potential therapeutic impact of docetaxel resistance in TNBC.

PurposeTo compare survival in different strategies, preoperative systemic treatment versus upfront surgery, in HER2-positive early breast cancer patients in the real world.MethodsAccording to the actual upfront treatment, eligible patients from 2012 to 2015 were classified as preoperative systemic treatment or upfront surgery group prospectively. The primary endpoint is disease-free survival; the second endpoint is overall survival. All the outcomes were examined in the propensity score matching model and inverse probability of treatment weighting model.ResultsIncluded in the analysis were 1,067 patients (215 in the preoperative systemic treatment group, 852 in the upfront surgery group). In the propensity score matching model (matching at 1:1 ratio), the disease-free survival of the preoperative systemic treatment group was significantly higher than that of the upfront surgery group (hazard ratio, 0.572, 95%CI, 0.371–0.881, P, 0.012). In the inverse probability of treatment weighting model, there was no significant difference in disease-free survival between the two groups (hazard ratio, 0.946, 95%CI, 0.763–1.172, P, 0.609). For overall survival, there was no significant difference between the two groups.ConclusionThe HER2-positive patients who accepted preoperative systemic treatment had better disease-free survival than those who underwent upfront surgery by real-world statistic methods.Clinical Trial RegistrationClinicaltrials.gov, identifier NCT04249440.

Early breast cancer with one or two sentinel lymph nodes (SLNs) may omit axillary lymph node dissection (ALND) if followed by radiotherapy. However, only less than one-third of the patients have positive non-SLNs and can truly benefit from radiotherapy. Before any regional treatment decision, the risk of non-SLN metastasis must be identified. The authors previously developed a predictive model for non-SLN involvement using CK19 mRNA and contrast-enhanced ultrasound (CEUS) score in a training set. They designed a further study to evaluate the predictive effect using the model prospectively in a validation set of one or two involved SLNs. This study identified early breast cancer patients at Zhejiang Cancer Hospital from July 2017 to June 2018. The CK19 mRNA tested by quantitative real-time polymerase chain reaction and CEUS scores were collected before surgery. Patients with one or two involved SLNs were enrolled and underwent ALND. The estimated percentage of non-SLN involvement was calculated by the authors’ model formula and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. The false-negative rates, predictive accuracy, and area under curve (AUC) were compared between two predictive models. The study enrolled 235 patients, and 35.36% (83/235) of them had non-SLN involvement. The authors’ model had a false-negative rate of 6% and an accuracy of 94.9%. The AUC was 0.952 (95% confidence interval [CI] 0.922–0.982), which was significantly higher than that of the MSKCC model at all three cutoff value levels. The authors’ model, using CK19 mRNA and the CEUS score, showed the potential predictive value of non-SLNs before surgery for early breast cancer patients. NCT02992067, NCT03280134.

Thermoelectric modules are usually sandwiched between hot-side and cold-side heat exchangers to generate electrical power. But the sandwiched structures are unsuitable for recuperators because large thermal resistance caused by the thermoelectric modules significantly reduces the heat transfer efficiency. In order to maintain heat transfer efficiency and generate more electrical power, a novel concept of a thermoelectric generator integrated recuperator is proposed, with fins made of thermoelectric materials rather than steel. A numerical model is developed using FLUENT software with User Defined Function codes. Compared with conventional plate-fin recuperators, the new recuperator has similar thermal-hydraulic performance and generates additional electrical power. The effects of Reynolds number on open circuit voltage, internal resistance, heat transfer, output power, and pumping power are studied. The optimum hot gas velocity is 1.5 m/s, which produces a temperature difference of 147.6 K, an open circuit voltage of 31.5 mV, and an output power of 0.23 mW. The Taguchi method is employed to design numerical cases for geometrical optimization. Results show that the effect order is: channel width > TE fin thickness > TE fin height. The optimum values of channel width, fin thickness, and height are 1 mm, 3 mm, and 1 mm, respectively.

BACKGROUND Menopausal syndrome (MPS) is common in pre/peri-menopausal breast cancer patient receiving luteinizing-hormone releasing hormone analogue (LHRHa). According to the results of TEXT & SOFT study, it could affect patients' life quality seriously and even caused 8%˜23% treatment break. Cimicifuga racemosa (Remifemin) is previously proved effective for MPS in nature menopause patients. We aim to design a prospective randomized research for investigating the effect of Remifemin on MPS which caused by LHRHa in breast cancer (NCT03339882). METHODS The pre/peri-menopausal patients diagnosed as early breast cancer planning for LHRHa were identified and randomly divided into two groups after surgery and chemotherapy if necessary: the Remifemin group (Remifemin 20mg twice a day for 12 weeks) and the control group. The primary endpoint is Kupperman menopause index (KMI). The estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH) levels in blood were also evaluated. RESULTS From January 2017 to December 2017, totally 85 patients (42 in Remifemin group and 43 in control group) were enrolled in Zhejiang Cancer Hospital and there were no significant differences in baseline characteristics including age, BMI, tumor stage, ER, PR, HER2, KMI and hormone levels between two groups (Table 1). At the time of 4, 8, 12 weeks after treatment, the KMI of Remifenmin group were all significantly lower than control group (Table 2, P0.05).There was no significant difference in endometrial thickness, ovarian cyst and Uterine fibroids except cervical cyst (P=0.02). CONCLUSION The use of Remifemin is oncological safe and reliable in preventing MPS which caused by LHRHa in breast cancer. The clinical characteristics of two groups Remifemin groupControl groupP n=42n=43 N(%)N(%) Age(years) 37.74±6.6037.16±6.280.68BMI (body mass index) 21.90±2.8321.65±3.010.69T stage02(4.76)2 (4.65)0.16 113 (30.95)22 (51.16) 227 (64.29)19 (44.19) N stage021 (50.00)24 (55.82)0.63 110 (23.81)12 (27.91) 26 (14.29)5 (11.63) 35 (11.90)2 (4.65) ERPositive30 (71.43)35 (81.40)0.28 Negative12 (28.57)8 (18.60) PRPositive30 (71.43)32 (74.42)0.76 Negative12 (28.57)11 (25.58) HER2Positive8 (19.05)10 (23.26)0.64 Negative34 (80.95)33 (76.74) Category of LHRHaGoserelin32 (76.19)28 (65.12)0.26 Leuprorelin10 (23.81)15 (34.88) Category of endocrine drugNone10 (23.81)6 (13.95)0.20 SERM5 (11.90)11 (25.58) AI27 (64.29)26 (60.47) The endpoints of two groups Remifemin groupControl groupP n=42n=43 KMI*Base line2.45±1.452.30±1.360.62 4th week3.83±1.868.37±4.19 Citation Format: Yu X, Wang C, Liang C, Xuan H, Yang H. Cimicifuga racemosa extract prevents menopausal syndrome in LHRHa treatment of breast cancer: A prospective randomized research [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-11.

In this paper, an optimization method combined computational fluid dynamics model (CFD), back propagation neural network (BPNN) model and genetic algorithm (GA) is proposed to optimize the performance of a novel concept of thermoelectric generator integrated recuperator (TEGR). Three geometrical parameters of TEGR including fin thickness, fin pitch and fin height are set as optimization variables. The CFD calculations using thermoelectric-hydraulic coupled model are used to obtain a large number of samples to train the BPNN model. It is found that the ‘3-5-2’ BPNN model is suitable for dealing with the present sample data. And genetic algorithm is used to search for the optimal solution in consideration of the power output and cost of TEGR. The predicted values of the optimization method are in good agreement with the numerical values of CFD.

Background As the critical regulators for tumorigenesis and progression, long-noncoding RNAs (lncRNAs) are becoming novel prognostic biomarkers for tumor patients. By the levels of lncRNAs expression, the patients with breast carcinoma may be divided into subgroups with different risk scores. Nevertheless, there is limited evidence to evaluate the role of lncRNAs in the prognosis of breast carcinoma. The present study aimed to construct lncRNA signatures for prognostic analysis and assist clinicians in choosing optimal therapies. Methods Abnormal expression profiles of breast cancer-associated lncRNAs were analyzed based on the TCGA datasets. Univariate and multivariate Cox regression analysis was used to build a prognostic risk signature according to the lncRNAs expression. The prognostic ability of this signature was verified in various subgroups. Functional enrichment analysis was employed to reveal the potential roles of these predictive lncRNAs in cancer-related biological processes and pathways. Results Compared with normal breast tissues, the differential analysis demonstrated that 286 lncRNAs were abnormally expressed in breast carcinoma. A four-lncRNA signature (RP1-193H18.2, AL022341.3, WDR86-AS1, LINC00511) was found to be closely related to the prognosis of breast carcinoma. The four-lncRNA signature could also qualify the magnitude of treatment benefits for different breast cancer subtypes. Additionally, it was an independent risk factor out of other clinicopathological parameters based on the multivariate Cox analysis. We also uncovered that the four predictive lncRNAs are involved in multiple cellular progression and pathways of breast cancer. Conclusions The four-lncRNA signature could be an essential reference for prognostic prediction and making therapeutic strategies.

Purpose To investigate whether estrogen receptor (ER), progesterone receptor (PR) and Ki-67 expression discordance before and after neoadjuvant chemotherapy (NAC) correlates with prognosis and treatment of breast cancer patients. Methods The study cohort included 482 breast cancer patients at the Zhejiang Cancer Hospital from January 1, 2008, to December 31, 2018. Core needle biopsies and excised tissue biopsies pre- and post-NAC were obtained. Immunohistochemistry was used to determine ER, PR and Ki-67 status. The relationship between biomarker discordance before and after NAC and clinicopathological features was compared retrospectively. Results ER (n = 482), PR (n = 482) and Ki-67 (n = 448) expression was assessed in the same lesion pre- and post-NAC. Discordance in the three markers pre- and post-NAC was observed in 50 (10.4%), 82 (17.0%) and 373 (77.4%) cases, respectively. Positive-to-negative PR expression changes were the most common type of discordance observed. The risk of death in patients with a PR positive-to-negative conversion was 6.58 times greater than for patients with stable PR expression. The risk of death in patients with increased Ki-67 expression following NAC treatment was 2.05 times greater than for patients with stable Ki-67 expression. Conclusion Breast cancer patients showed changes in ER, PR and/or Ki-67 status throughout NAC, and these changes possibly influenced disease-free survival and overall survival. A switch to negative hormone receptor expression with increased Ki-67 expression following NAC could be indicators of a worse prognosis. Biomarker expression investigations following NAC may potentially improve patient management and survival.

To help study the performance of thermoelectric power generators in conditions where there are large temperature differences between the hot-side heat exchanger and the cold-side heat exchanger, this paper presents a simplified numerical model that includes temperature-dependent properties of thermoelectric materials. Specifically, the temperature difference is added into the calculations of the current across thermoelectric legs. The results indicate that the simplified numerical model could reduce calculation time without reducing calculation accuracy. The variable physical properties of thermoelectric materials should be considered in the counter-flow arrangement at high temperature, but they can be neglected in the co-flow arrangement. The inlet temperature of hot fluid and the variable physical properties of thermoelectric materials have a coupling influence on the performance of thermoelectric power generation, which could change the variation trend of output power. The performance of thermoelectric power generation for the counter-flow arrangement is better than that for the co-flow arrangement, especially with high heat transfer coefficients and long channel lengths. When the the various physical properties of thermoelectric materials are considered, the maximum output power and efficiency occur at ratios of load resistance to internal resistance of about 1.5–1.8 for output power and 1.7–2 for efficiency.

We aimed to investigate the potential role and regulatory mechanism of long noncoding RNA tumor-associated lncRNA expressed in chromosome 2 (TALNEC2) in breast cancer. The expression of TALNEC2 in breast cancer tissues and cells were investigated. MCF-7 and MDA-MB-231 cells were transfected with small interfering RNA (siRNA) duplexes for targeting TALNEC2 (si-TALNEC2), enhancer of zeste homolog 2 (EZH2; si-EZH2) and p57KIP2 (si-p57 KIP2 ), and their corresponding controls (si-NC). The viability, colony forming ability, cell cycle, apoptosis, and autophagy of transfected cells were assessed. The expressions of p-p38 mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathway-related proteins were investigated. The results showed that TALNEC2 was highly expressed in breast cancer tissues and cells. Knockdown of TALNEC2 significantly inhibited the malignant behaviors of MCF-7 and MDA-MB-231 cells, including inhibiting cell viability and colony forming, arresting cell cycle at G0/G1 phase, inducing cell apoptosis, and promoting cell autophagy. EZH2 was a TALNEC2 binding protein, which was upregulated in breast cancer tissues and cells and could negatively regulate p57 KIP2 . Effects of TALNEC2 knockdown on malignant behaviors of MCF-7 cells were reversed by p57 KIP2 knockdown. The expressions of p-p38, RelA, and RelB in MCF-7 cells were decreased after knockdown of TALNEC2 or EZH2, which were reversed by knockdown of p57 KIP2 concurrently. In conclusion, TALNEC2 may play an oncogenic role in breast cancer by binding to EZH2 to target p57 KIP2 . Activation of p-p38 MAPK and NF-κB pathways may be key mechanisms mediating the oncogenic role of TALNEC2 in breast cancer. TALNEC2 may serve as a promising target in the therapy of breast cancer.

To explore the role of ribosomal protein S15A (RPS15A) in breast cancer. The Oncomine database was used to compare the expression of RPS15A in human breast cancer tissues and normal tissues. RPS15A in breast cancer cell line ZR-75-30 and BT474 was specifically knocked down using lentivirus-mediated short hairpin RNAs (shRNAs). RPS15A knockdown efficiency was validated by quantitative polymerase chain reaction and western blot analysis. Subsequently, the functional effects of RPS15A on proliferation of breast cancer cells were investigated by MTT, colony formation and flow cytometry assays. Functional analysis indicated that RPS15A knockdown could inhibit cell proliferation, induced cell cycle arrest and apoptosis. Mechanism analysis revealed RPS15A mediated apoptosis via activating of caspase-3 and PARP cleavage, upregulating of Bad and BAX and downregulating of Bcl-2. Our preliminary study highlighted the importance of RPS15A in breast cancer growth. The inhibition of RPS15A may be a promising therapeutic target for breast cancer treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10616-018-0221-9) contains supplementary material, which is available to authorized users.

The thermoelectric material is considered to a good choice to recycle the waste heat in the power and energy systems because the thermoelectric material is a solid-state energy converter which can directly convert thermal energy into electrical energy, especially suitable for high temperature power and energy systems due to the large temperature difference. However, the figure of merit of thermoelectric material is very low, and the thermoelectric power of generator system is even lower. This work reviews the recent progress on the thermoelectric power generator system from the view of heat transfer, including the theoretical analysis and numerical simulation on thermoelectric-hydraulic performance, conventional heat transfer enhancement technologies, radial and flow-directional segmented enhancement technologies for the thermoelectric power generator system. Review ends with the discussion of the future research directions of numerical simulation methods and heat transfer enhancement technologies used for the thermoelectric power generator in high temperature power and energy systems.

In typical gas-to-liquid thermoelectric generators for waste heat recovery, the stream-wise gas temperature drop in the hot-side heat exchanger leads to the decrease of power output of the whole system. Denser fins are usually arranged on the downstream of the hot-side heat exchanger to improve the uniformity of temperature field and thus the total power output performance of thermoelectric generators when the steam-wise temperature drop is small, but it is not benificial when the steam-wise temperature drop is large. This work investigates the effect of configuration of winglet vortex generators on the performance of thermoelectric generator system. Three sets of hot-side heat exchangers, including a heat exchanger with smooth channel, a heat exchanger with uniform configuration of winglet vortex generators and a heat exchanger with non-uniform configuration of winglet vortex generators, are tested in a gas-to-liquid thermoelectric generators experimental system. The hot-side Reynolds number ranges from 3000 to 6400 and the hot-side inlet temperature is within 523–553 K. The experimental results show that the total and net power output of thermoelectric generator under matched load resistance with uniform heat exchanger can respectively outperform that with smooth heat exchanger by 97.5% and 77.7% in average, whereas that with non-uniform heat exchanger by 189.1% and 177.4% in average. Since the uniform and non-uniform heat exchangers have the same number but different configuration of winglet vortex generators, this kind of active cascade control of heat transfer enhancement elements is proved to be effective in improving the power output of thermoelectric generator system without increasing pumping power.

The 2010 American Society of Clinical Oncology guidelines have reduced the immunohistochemistry cut-off value for determining estrogen receptor b positivity from 10 to 1% of stained cells in breast cancer. In clinical practice, low-hormone receptor positive (low HR+) tumors are classified in the luminal subtype, although they exhibit aggressive features and poor prognosis. Information regarding the prognosis of patients with breast cancer following treatment with optimal endocrine therapy and neoadjuvant chemotherapy (NAC) is currently lacking. In the present study, the differences in clinical characteristics and survival of patients with breast cancer were compared among those with low and high HR+ breast cancer who received NAC. Furthermore, the effects of different types of endocrine therapies on the prognosis of patients with breast cancer were compared. The study population comprised patients with primary breast cancer who were treated at the Zhejiang Cancer Hospital between January, 2007 and December, 2017. Patients were divided into three groups based on the results of immunohistochemistry: HR+ (positive staining >10%), HR- (positive staining

Background/Aims: Next-generation sequencing (NGS) has revealed abundant long noncoding RNAs (lncRNAs) that have been characterized as critical components of cancer biology in humans. The present study aims to investigate the role of the lncRNA KCNQ1OT1 in breast cancer (BRCA) as well as the underlying molecular mechanisms and functions of KCNQ1OT1 involved in the progression of BRCA. Methods: The Cancer Genome Atlas (TCGA) and StarBase v2.0 were used to obtain the required gene data. Dual luciferase reporter gene assays were conducted to verify the relevant intermolecular target relationships. QRT-PCR and Western blot were performed to measure the expression levels of different molecules. Cell proliferation was detected by using the MTT and colony formation assays, while cell migration and invasion were examined by transwell assay. Variations in cell apoptosis and cell cycle were determined through flow cytometry. A tumor xenograft model was applied to assess tumor growth in vivo. Results: KCNQ1OT1 was found to be remarkably highly expressed in BRCA tissues and cells. KCNQ1OT1 modulated CCNE2 through sponging miR-145 in BRCA. KCNQ1OT1 promoted tumor growth in vivo by regulating miR-145/CCNE2. Conclusion: The KCNQ1OT1/miR-145/CCNE2 axis plays a critical regulatory role in BRCA, potentially giving rise to BRCA tumorigenesis and progression. These findings provide valuable evidence for improving the diagnosis and treatment of BRCA in the future.

We aimed to investigate the potential role and regulatory mechanism of long noncoding RNA tumor-associated lncRNA expressed in chromosome 2 (TALNEC2) in breast cancer. The expression of TALNEC2 in breast cancer tissues and cells were investigated. MCF-7 and MDA-MB-231 cells were transfected with small interfering RNA (siRNA) duplexes for targeting TALNEC2 (si-TALNEC2), enhancer of zeste homolog 2 (EZH2; si-EZH2) and p57

Breast cancer is the cause for highest number of cancer-related death among women worldwide. This study was focused on investigating the role of zinc-finger protein X-linked (ZFX) in human breast cancer. Expression levels of ZFX were analyzed in 99 patients and four breast cancer cell lines. Lentivirus-mediated RNA interference was applied to silence ZFX expression, and the effects of ZFX knockdown on the growth of breast cancer cells were investigated. The immunohistochemical expression of ZFX was higher in more advanced tumor tissues. ZFX was also overexpressed in multiple breast cancer cell lines. Knockdown of ZFX inhibited cell proliferation and colony formation of MCF-7 and MDA-MB-231 cells. Moreover, ZFX silencing resulted in cell cycle arrest at G0/G1 phase. Depletion of ZFX decreased the phosphorylation level of AKT and increased the phosphorylation level of ERK2 and the expression of cyclin D1, which is involved in cell survival and cell cycle regulation. These findings suggest that ZFX plays an important role in breast cancer development and could be a potential therapeutic target for breast cancer.

The relationship between lithium-ion battery performance and operating temperature is of significance in designing battery thermal management system (BTMS). In this study, two different thermal conditions, namely constant temperature condition and near-adiabatic condition are established to explore charging/discharging characteristics and heat generation behaviors of the lithium-ion battery with Li(NixCoyAlz)O2 cathode. The objective of creating near-adiabatic condition is to discover the effect of the heat generated by battery itself on charging/discharging characteristics. The experimental results show that the battery charging characteristics are nearly independent on the charging temperature ranged from 20 °C to 40 °C, while the battery charging/discharging performance degrade dramatically for the battery temperature lower than 20 °C. Although the heat generated by battery itself may accelerate battery degradation during cycling due to the adverse effect of excessive temperature, however it improves the discharging performance in a suitable temperature range. This implies that a battery pack may have an excellent discharging performance without BTMS intervention at a moderate discharging rate (e.g., 0.5 C). The irreversible heat could be regarded as the sole heat source term to simplify the battery thermal model due to negligible thermal effect caused by the small amount of reversible heat when the battery is discharged at higher discharging rates.

The effective thermal conductivities (ETCs) of porous electrodes in electrolyte are of rather significance for determining the thermal conductivity of Li-ion battery which is an important factor in designing battery thermal management system and predicting battery thermal behaviour. In this study, the representative Li-ion battery consisting of a Li(NiCoMn)O2 positive electrode and a graphite negative electrode was chosen to explore the ETCs of porous electrodes. The effects of ETCs of porous electrodes on the Li-ion battery’s thermal conductivity were firstly discussed, and the ETCs were analysed based on its internal configuration and basic assumptions. Most importantly, the ETCs bounds of porous electrodes were acquired using basic thermal conductivity models and the limits of ETCs were obtained based on Maxwell 2 model combined with volume fractions of electrolyte. The results show that the ETCs of porous electrodes in electrolyte are obviously lower than the thermal conductivities of active materials, namely Li(NiCoMn)O2 and graphite. In addition, the ETCs of porous electrodes are not constant but variable values caused by the variation of volume fractions of electrolyte in porous electrodes which indicates that the volume fractions of electrolyte should be considered for accurately estimate the thermal conductivity of commercial Li-ion battery.

Ethnopharmacological relevance Cimicifuga racemose is previously proved effective on nature menopausal syndrome (MPS). However, its clinical value in treating with MPS induced by luteinizing-hormone releasing hormone analogue (LHRH-a) therapy of pre-/peri-menopausal breast cancer patients is still unknown. Aim of study This perspective randomised-design study is to investigate the effect and safety of cimicifuga racemosa on MPS induced by LHRH-a in breast cancer (clinical trial registered: NCT03339882 ). Materials and methods Breast cancer patients planning for LHRH-a treatment were randomly divided into 2 groups. The control group which was being treated with the standard treatment of LHRH-a. The other group was being treated with Remifemin, the commercialized product of cimicifuga racemose extract, combined with LHRH-a, called Remifemin group. Our main endpoint was Kupperman menopause index (KMI). Hormone levels in peripheral blood and gynecological complications were also evaluated. Results Totally, 85 patients (42 in Remifemin group and 43 in control group) were enrolled in Zhejiang Cancer Hospital. At the 4th, 8th and 12th week after using LHRH-a, the KMI were all significantly lower in Remifemin group than in control group (P 0.05). Conclusions Cimicifuga racemose is effective, oncological safe and reliable for treatment of MPS caused by LHRH-a in breast cancer.

e12059 Background: Axillary lymph node (LN) involvement is significantly related with high recurrent risk and influenced by tumor size, histologic grade and subtype in early breast cancer. For hormone receptor positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) breast cancer without LN involvement, 21-gene recurrence score (RS) provides an effective method evaluating the risk of recurrence and metastasis. But the correlation between RS and LN involvement is not clear currently. To investigate the effect of RS on LN involvement, we designed a retrospective cohort study based on the data of tumor size-match LN+/- HR+HER2- breast cancer. Methods: The luminal type (ER+, PR+ and HER2-) early breast cancer (cT1-2) patients with 1~3 LN+ were enrolled and were tumor size-match paired (1:3) with those LN- during the same period. We compared the 21-gene RS between the LN+ and LN- group by univariate and multivariate analyses. Results: From April 2016 to May 2018, there were 65 LN+ cases undergoing 21-gene test included and 195 LN- cases were paired. With tumor size matched, the LN+ group had significantly younger age, more positive family history, higher histologic grade and higher RS than LN- group. All those factors, excepted histologic grade, were further confirmed in multivariate analysis (Table). Conclusions: After adjusted by tumor size, RS may have a significantly independent correlation with LN involvement in HR+HER2- early breast cancer. Total HR+HER2- cases’ tumor size-match paired (1:3) clinic pathologic and RS data. Clinical trial information: NCT03638648. [Table: see text]

559 Background: Early breast cancer (cT1-2N0) with one or two sentinel lymph node (SLN) involved may avoid axillary lymph node dissection (ALND) if follow by radiotherapy supported by Z0011 and AMAROS trials. However, only less than one-third of those patients have positive non-sentinel lymph node (nSLN) and can truly benefit from radiotherapy or ALND in those two trials. It is necessary to identify the risk of nSLN metastasis before local treatment decision. We previously developed a predictive model for nSLN involvement using circulating CK19 mRNA level combined with contrast-enhanced ultrasound (CEUS) score (ASCO2017 poster 239, NCT02992067) in a training set. To evaluate the predict effect of this model, we designed a further study using the model prospectively in a validation set (NCT03280134). Methods: We identified early breast cancer cases in Zhejiang Cancer Hospital from July 2017 to June 2018. The level of circulating CK19 mRNA tested by qRT-PCR and CEUS scores were collected before surgery in each case. Patients with 1~2 SLN involved were enrolled and continued for ALND. The estimated percentage of nSLN-involved were calculated both by our model formula and the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram. The predictive accuracy and false negative rates (FNR) were evaluated and the area under curve (AUC) was compared between two predictive models. Results: Totally, 235 patients diagnosed as early breast cancer with 1~2 SLN involved were enrolled and 35.36% of them were nSLN involved after ALND. The total accuracy and FNR by our model for nSLN-involved prediction was 94.89% and 6.02%, respectively. The AUC was 0.952 (95%CI, 0.922~0.982), significantly higher than that in MSKCC model 0.880 (95%CI, 0.833~0.927). Furthermore, only CK19 mRNA level (HR = 40.091, 95%CI, 13.663~117.635) and CEUS score (HR = 2.009, 95%CI 1.158~3.485) are significantly related to nSLN involvement in both univariate and multivariate analysis, adjusted by age, menopause statue, tumor size, histological grade, estrogen receptor, progesterone receptor and human epidermalgrowth factor receptor-2 expression. Conclusions: Our model using CK19 mRNA and CEUS score showed potential predictive value of nSLN before surgery in early breast cancer patients. Further validation in larger multicenter cohort is warranted before changing clinical practice.

Background Male breast cancer (MBC) is known to be rare compared with female breast cancer (FBC) and to account for only 1% of all breast cancers. To date, male patients diagnosed with breast cancer are normally treated based on the guidelines for FBC. Specifically, studies have found that diagnosing and treating MBC patients under the guidelines for the treatment of post-menopausal FBC are more favorable than are those of pre/peri-menopausal FBC from a physiological perspective because MBC and post-menopausal FBC patients show high estrogen receptor (ER) expression in the tumor and low estrogen expression in the body. In this medical study, we aimed to examine whether MBC actually has the same prognosis as post-menopausal FBC. Method We identified MBC patients who were diagnosed as operable and who completed clinical treatment and we used follow-up data that were collected from January 2001 to January 2011. Each MBC patient was paired with four FBC patients who were diagnosed within the same period (two were pre/peri-menopausal, and two were post-menopausal). We compared disease-free survival (DFS) and overall survival (OS) among three groups, i.e., pre/peri-menopausal FBC (group A), post-menopausal FBC (group B) and MBC (group M), using the Kaplan-Meier method and a Cox proportional hazards regression model. We also evaluated the clinical characteristics of breast cancer patients using t-tests and chi-square tests. We used ten consecutive years of data that were collected at Zhejiang Provincial Cancer Hospital. Results We identified 91 MBC cases for group M, 182 FBC cases for group A and 182 FBC cases for group B. The median follow-up period was 112 months. MBC cases were much more frequently ER positive than those of group A and group B (p

11539 Background: According to Z0011 and AMAROS trials, patients with breast cancer stage cT1~2cN0 and sentinel lymphnode (SLN) 1~2 involvement can avoid axillary lymphnode dissection (ALND). But the risk of non-sentinel lymphnode (nSLN) involvement in those early stage patients is still unclear and it is difficult to predicting the risk before surgery. Our previous study showed CK19 mRNA in peripheral blood had predicative value of nSLN involvement. Also, contrast-enhanced ultrasound (CEUS) is a new effective method exmaming axillary lymph node. We aim to establish a prediction model for nSLN involvement in early breast cancer using CK19 combined with CEUS score. Methods: We identified 119 cases diagnosed early breast cancer (stage cT1~2cN0 and 1~2 SLNs involvement as in Z0011 and AMAROS trials) from Oct 2015 to Nov 2016 in Zhejiang Cancer Hospital. The CK19 mRNA of peripheral blood by RT-PCR and CEUS score of axillary lymph nodes were acquired before surgery. We used logistic regression analysis for filtering out valuable predictive clinical parameters and establishing formulas to calculate the probability of nSLN involvement. Our model was compared with Memorial Sloan Kettering Cancer Center (MSKCC) nomogram, which is one of the most reliable and validated methods for predicting of nSLN. Results: The histological grade, CK19 and CEUS score were screened by logistic regression analysis into the formula to calculate the probability of nSLN involvement. The sensitivity, specificity, total accuracy of this model was 89.13%, 80.82% and 84.03%, respectively. The false negative rate was 10.87%. The model had high quality of consistency (Kappa 0.675, p < 0.01) and goodness of fit (likelihood-ratio test, -2log liklihood = 84.607). The area under curve (AUC) of ROC was significantly higher (P < 0.01) in our model (0.914, 95%CI, 0.863~0.965) than in MSKCC nomogram (0.563, 95%CI, 0.459~0.667). Conclusions: The prediction model based on CK19 and CEUS score has satisfying sensitivity, specificity and accuracy, more effective than MSKCC nomogram. It is a valuable model of evaluating the risk of nSLN involvement in early breast cancer before surgery, picking out the patients who can truly avoid ALND.

Background Male breast cancer (BC) is a kind of rare tumour. There were few researches concerning the effect of chemotherapy for it. The purpose of this study is to estimate the value of chemotherapy on prognosis in male BC. Patients and methods Complete clinical and pathological information of male BC were collected from January 1990 to January 2008 in Zhejiang Cancer Hospital in China. 134 cases of male BC were included for analysis and separated into two groups based on receiving chemotherapy or not receiving chemotherapy. The disease-free survival (DFS) and overall survival (OS) between chemotherapy group and non-chemotherapy group were compared with Kaplan-Meier survival curve. Stratified analysis was used to evaluate the strength of the association between chemotherapy and each risk factor. Multivariate analysis was conducted by using COX proportional hazard regression model. Results There were 58.21% (78/134) cases who underwent chemotherapy and 41.79% (56/134) cases without chemotherapy. There were 20 cases (25.64%) with recurrence/metastasis in patients with chemotherapy and six cases (10.71%) in patients without chemotherapy. The mean DFS time of male BC with chemotherapy and non-chemotherapy is 150.87 and 154.13 months, respectively (χ 2 =3.825, p=0.050). The mean OS time of male BC with chemotherapy and non-chemotherapy is 155.33 and 154.26 months, respectively (χ 2 =2.542, p=0.111). COX proportional hazard regression model showed that the two groups had similar DFS (HR=0.386, p=0.165), while chemotherapy might be a protective fact on OS (HR=0.140, p=0.026). Conclusion The utility of chemotherapy should be considered in the high risk level of recurrence/metastasis in male BC.

Paired box 6 (PAX6) plays a significant role in the development of human neuroectodermal epithelial tissues. Previous studies have suggested that the PAX6 promoter is hypermethylated in breast cancer and that it is involved in breast cancer cell proliferation. The present study aimed to investigate the expression of PAX6 in invasive breast cancer tissues, and to evaluate its prognostic significance. Immunohistochemistry (IHC) was used to detect PAX6 expression on a breast cancer tissue microarray containing tissues from 111 patients. Associations of PAX6 expression with staging and prognosis were analyzed. PAX6 was mainly expressed in the nucleus. The PAX6 staining intensity was not associated with age, histological grade, lymph node status, tumor size, or progesterone receptor and human epidermal growth factor receptor 2 expression (all P>0.05). A high level of PAX6 staining was more frequent in estrogen receptor (ER)-negative cases compared with ER-positive cases (43.9 vs. 25.7%; P=0.049). After a median follow-up time of 110 months, the patients with low PAX6 expression exhibited an improved survival rate compared with the patients with high PAX6 expression (P

e13095Background: Mucinous breast carcinoma (MC) is a special type of breast cancer, comprising approximately 4% of all invasive breast cancers. Pathologically, it is divided into two main subtypes, the pure type and the mixed type. In this study, we aimed to report the last 10-year experience of the Zhejiang Cancer Hospital in China regarding MC with its clinical characteristics and outcome. Methods: We used consecutive ten years of data that were collected at Zhejiang Cancer Hospital from January 2001 to January 2011.All patients were divided into three groups: patial mixed mucinous breast carcinoma (pMMC) was defined as less than 50% mucinous component; main mixed mucinous breast carcinoma (mMMC) was defined as mucinous component accounted from 50% to 90%; PMC was defined as mucinouscomponent accounted more than 90%.The clinical pathological characteristics included age at diagnosed, menopausal status, tumor size, clinical stage, lymph node metastasis(LN+), estrogen receptor (ER), prostrogen receptor (...

562Background: In our previous study, goserelin has been reported downregulating the estradiol level, breast density and endometrial thickness in Chinese pre-/peri-menopausal hormone positive (HR+)...

e12047 Background: CK19 mRNA level of lymph node tissue detected by RT-PCR has been used in sentinel lymph node biopsy (SLNB) in breast cancer. This study was designed to figure out whether CK19 ex...

e11524 Background: In our previous study (published in The Breast 2013), we concluded that the molecular subtypes of male breast cancer (MBC) play important role in prognoses. The aim of this study...