In vitro efficacy of Er:YAG laser-activated irrigation versus passive ultrasonic irrigation and sonic-powered irrigation for treating multispecies biofilms in artificial grooves and dentinal tubules: an SEM and CLSM study.

BACKGROUND: Multispecies biofilms located in the anatomical intricacies of the root canal system remain the greatest challenge in root canal disinfection. The efficacy of Er:YAG laser-activated irrigation techniques for treating multispecies biofilms in these hard-to-reach areas has not been proved. The objective of this laboratory study was to evaluate the effectiveness of two Er:YAG laser-activated irrigation techniques, namely, photon-induced photoacoustic streaming (PIPS) and shock wave-enhanced emission photoacoustic streaming (SWEEPS), in treating multispecies biofilms within apical artificial grooves and dentinal tubules, in comparison with conventional needle irrigation (CNI), passive ultrasonic irrigation (PUI), and sonic-powered irrigation (EDDY). Two types of multispecies root canal biofilm models were established in combination with two assessment methods using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) with the aim to obtain more meaningful results. METHODS: Ninety extracted human single-rooted premolars were chosen for two multispecies biofilm models. Each tooth was longitudinally split into two halves. In the first model, a deep narrow groove was created in the apical segment of the canal wall. After cultivating a mixed bacterial biofilm for 4 weeks, the split halves were reassembled and subjected to five irrigation techniques: CNI, PUI, EDD, PIPS, and SWEEPS. The residual biofilms inside and outside the groove in Model 1 were analyzed using SEM. For Model 2, the specimens were split longitudinally once more to evaluate the percentage of killed bacteria in the dentinal tubules across different canal sections (apical, middle, and coronal thirds) using CLSM. One-way analysis of variance and post hoc multiple comparisons were used to assess the antibiofilm efficacy of the 5 irrigation techniques. RESULTS: Robust biofilm growth was observed in all negative controls after 4 weeks. In Model 1, within each group, significantly fewer bacteria remained outside the groove than inside the groove (P < 0.05). SWEEPS, PIPS and EDDY had significantly greater biofilm removal efficacy than CNI and PUI, both from the outside and inside the groove (P < 0.05). Although SWEEPS was more effective than both PIPS and EDDY at removing biofilms inside the groove (P < 0.05), there were no significant differences among these methods outside the groove (P > 0.05). In Model 2, SWEEPS and EDDY exhibited superior bacterial killing efficacy within the dentinal tubules, followed by PIPS, PUI, and CNI (P < 0.05). CONCLUSION: Er:YAG laser-activated irrigation techniques, along with EDDY, demonstrated significant antibiofilm efficacy in apical artificial grooves and dentinal tubules, areas that are typically challenging to access.

3D Extruded Graphene Thermoelectric Threads for Self-Powered Oral Health Monitoring.

Flexible sensors play a crucial role in intelligent electronic devices, while strain-sensing is the fundamental feature for these sensors of different fields. Therefore, developing high-performance flexible strain sensors is essential for building the next generation of smart electronics. Here, a self-powered ultrasensitive strain sensor based on graphene-based thermoelectric composite threads through a simple 3D extrusion method is reported. The optimized thermoelectric composite threads show a large stretchable strain of over 800%. After 1000 cycles of bending, the threads still maintain excellent thermoelectric stability. The thermoelectric effect-induced electricity can realize ultrasensitive strain and temperature detection with high resolution. As wearable devices, the thermoelectric threads can also realize self-powered physiological signals monitoring, including the opening degree of mouth, occlusal frequency, and force of the tooth during the eating process. It provides significant judgment and guidance for promoting oral healthcare and developing good eating habits.

Cleaning and Disinfecting Oval-Shaped Root Canals: Ex Vivo Evaluation of Three Rotary Instrumentation Systems with Passive Ultrasonic Irrigation.

Background and Objectives: Successful root canal treatment depends on the thorough removal of biofilms through chemomechanical preparation. This study aimed to investigate and compare the cleaning and disinfecting efficiency of oval-shaped root canals using XP-endo Shaper (XPS), ProTaper Next (PTN), and HyFlex CM (HCM) in combination with passive ultrasonic irrigation (PUI). Materials and Methods: Ninety extracted teeth were contaminated and randomly divided into three groups: XPS, PTN, and HCM. Each group was assigned to three subgroups: subgroup A (sterile saline), subgroup B (3% sodium hypochlorite and 17% ethylenediaminetetraacetic acid), and subgroup C (3% sodium hypochlorite, 17% ethylenediaminetetraacetic acid, and PUI). Bacterial sampling was conducted both from baseline samples and samples after chemomechanical preparation. Scanning electron microscopy (SEM) was used to evaluate the residue bacterial biofilms, hard tissue debris, and smear layers on the buccolingual walls of oval-shaped root canals. Results: When combined with sterile saline, XPS demonstrated a higher reduction of bacterial counts and was more effective in eradicating Enterococcus faecalis in the middle third of the canals compared to the other instruments (p < 0.05). Additionally, when used with antimicrobial irrigants, XPS was more effective in disinfecting the coronal third of the canals than the other instruments (p < 0.05). Furthermore, XPS reduced hard tissue debris more effectively in the middle third of canals than in the apical third (p < 0.05). Conclusions: XPS outperforms PTN and HCM in disinfecting oval-shaped root canals. Despite the fact that combining XPS and PUI improves cleaning and disinfecting, removing hard tissue debris from the critical apical area remains challenging.

Nut consumption in association with overall mortality and recurrence/disease-specific mortality among long-term breast cancer survivors.

High nut consumption is associated with reduced total and certain cause-specific mortality in general populations. However, its association with cancer outcomes among long-term breast cancer survivors remains unknown. We examined the associations of nut consumption (including peanuts and tree nuts), assessed at 5-year postdiagnosis, with overall survival (OS) and disease-free survival (DFS) among 3449 long-term breast cancer survivors from the Shanghai Breast Cancer Survival Study, applying Cox regression analysis. During a median follow-up of 8.27 years post dietary assessment, there were 374 deaths, including 252 breast cancer deaths. Among 3274 survivors without previous recurrence at the dietary assessment, 209 developed breast cancer-specific events, that is, recurrence, metastasis or breast cancer mortality. At 5-year post dietary assessment (ie, 10-year postdiagnosis), regular nut consumers had higher OS (93.7% vs 89.0%) and DFS (94.1% vs 86.2%) rates. After multivariable adjustment, nut consumption was positively associated with OS (Ptrend  = .022) and DFS (Ptrend  = .003) following a dose-response pattern, with hazard ratios (95% confidence interval) of 0.72 (0.52-1.05) for OS and 0.48 (0.31-0.73) for DFS, for participants with greater than median nut intake compared with nonconsumers. The associations did not vary by nut type. Stratified analyses showed that the associations were more evident among participants with a higher total energy intake for OS (Pinteraction  = .02) and among participants with early stage (I-II) breast cancers for DFS (Pinteraction  = .04). The nut-DFS associations were not modified by estrogen receptor/progesterone receptor status or other known prognostic factors. In conclusion, nut consumption was associated with better survival, particularly DFS, among long-term breast cancer survivors.

Adherence to colonoscopy in cascade screening of colorectal cancer: A systematic review and meta-analysis.

BACKGROUND AND AIM: This study aims to systematically evaluate adherence to colonoscopy and related factors in cascade screening of colorectal cancer (CRC) among average-risk populations, which is crucial to achieve the effectiveness of CRC screening. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library for studies published in English up to October 16, 2020, and reporting the adherence to colonoscopy following positive results of initial screening tests. A random-effects meta-analysis was applied to estimate pooled adherence and 95% confidence intervals. Subgroup analysis and mixed-effects meta-regression analysis were performed to evaluate heterogeneous factors for adherence level. RESULTS: A total of 245 observational and 97 experimental studies were included and generated a pooled adherence to colonoscopy of 76.6% (95% confidence interval: 74.1-78.9) and 80.4% (95% confidence interval: 77.2-83.1), respectively. The adherence varied substantially by calendar year of screening, continents, CRC incidence, socioeconomic status, recruitment methods, and type of initial screening tests, with the initial tests as the most modifiable heterogeneous factor for adherence across both observational (Q = 162.6, P < 0.001) and experimental studies (Q = 23.2, P < 0.001). The adherence to colonoscopy was at the highest level when using flexible sigmoidoscopy as an initial test, followed by using guaiac fecal occult blood test, quantitative or qualitative fecal immunochemical test, and risk assessment. The pooled estimate of adherence was positively associated with specificity and positive predictive value of initial screening tests, but negatively with sensitivity and positivity rate. CONCLUSIONS: Colonoscopy adherence is at a low level and differs by study-level characteristics of programs and populations. Initial screening tests with high specificity or positive predictive value may be followed by a high adherence to colonoscopy.

MicroRNA-374b inhibits breast cancer progression through regulating CCND1 and TGFA genes.

Emerging evidence indicates that microRNAs (miRNAs) play a critical role in breast cancer development. We recently reported that a higher expression of miR-374b in tumor tissues was associated with a better disease-free survival of triple-negative breast cancer (TNBC). However, the functional significance and molecular mechanisms underlying the role of miR-374b in breast cancer are largely unknown. In this current study, we evaluated the biological functions and potential mechanisms of miR-374b in both TNBC and non-TNBC. We found that miR-374b was significantly downregulated in breast cancer tissues, compared to adjacent tissues. MiR-374b levels were also lower in breast cancer cell lines, as compared to breast epithelial cells. In vitro and in vivo studies demonstrated that miR-374b modulates the malignant behavior of breast cancer cells, such as cell proliferation in 2D and 3D, cell invasion ability, colony-forming ability and tumor growth in mice. By using bioinformatics tools, we predicted that miR-374b plays a role in breast cancer cells through negatively regulating cyclin D1 (CCND1) and transforming growth factor alpha (TGFA). We further confirmed that CCND1 and TGFA contribute to the malignant behavior of breast cancer cells in vitro and in vivo. Our rescue experiments showed that overexpressing CCND1 or TGFA reverses the phenotypes caused by miR-374b overexpression. Taken together, our studies suggest that miR-374b modulates malignant behavior of breast cancer cells by negatively regulating CCND1 and TGFA genes. The newly identified miR-374b-mediated CCND1 and TGFA gene silencing may facilitate a better understanding of the molecular mechanisms of breast cancer progression.

Prediction models for breast cancer prognosis among Asian women.

BACKGROUND: Robust and reliable prognosis prediction models have not been developed and validated for Asian patients with breast cancer, a rapidly growing yet understudied population in the United States. METHODS: We used longitudinal data from the Shanghai Breast Cancer Survival Study, a population-based prospective cohort study (n = 5042), to develop prediction models for 5- and 10-year disease-free survival (DFS) and overall survival (OS). The initial models considered age at diagnosis, tumor grade, tumor size, number of positive nodes, TNM stage, chemotherapy, tamoxifen therapy, and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status. We then evaluated whether the addition of modifiable lifestyle factors (physical activity, soy isoflavones intake, and postdiagnostic weight change) improved the models. All final models have been validated internally and externally in the National Cancer Database when applicable. RESULTS: Our final models included age at diagnosis, tumor grade, tumor size, number of positive nodes, TNM stage, chemotherapy, tamoxifen therapy, ER status, PR status, 6-month postdiagnostic weight change, interaction between ER status and tamoxifen therapy, and interaction between age and TNM stage. The internal validation yielded C-statistics of 0.76, 0.74, 0.78, and 0.75 for 5-year DFS, 10-year DFS, 5-year OS, and 10-year OS, respectively. The external validation yielded C-statistics of 5- and 10-year OS both at 0.78 for Chinese ethnicity, 0.79 for East Asian ethnicity, and 0.75 and 0.76 for all ethnic groups combined. CONCLUSION: We developed prediction models for breast cancer prognosis from a large prospective study. Our prognostic models performed very well in women from the United States-particularly in Asian American women-and demonstrated high prediction accuracy and generalizability.

Association between lincRNA expression and overall survival for patients with triple-negative breast cancer.

PURPOSE: Long intergenic non-coding RNAs (lincRNAs) are increasingly recognized as important regulators for pathogenesis and/or prognosis of breast cancer, including triple-negative breast cancer (TNBC) subtype. However, few previous studies used RNA-sequencing (RNA-Seq) technology, and none included an independent replication. METHODS: To systematically evaluate the association between expression of lincRNAs and TNBC survival, we examined lincRNA expression profiles in TNBC tissues using RNA-Seq data for 200 TNBC patients from the Shanghai Breast Cancer Survival Study (SBCSS) and Southern Community Cohort Study (SCCS). RESULTS: Twenty-five lincRNAs were found to be associated with overall survival (P < 0.05 and no significant heterogeneity across studies at Q statistic P > 0.1), and 61 lincRNAs were associated with disease-free survival (DFS). Among these, two lincRNAs (LINC01270 and LINC00449) were significantly associated with both worse overall survival and DFS and were expressed at significantly higher levels in tumor tissues compared with adjacent normal breast tissues (log2[Fold Change] > 0.5 and FDR < 0.05). We further evaluated the potential functions of LINC01270 and LINC00449 using in vitro functional experiments and found that siRNA-mediated knockdown of LINC01270 and LINC00449 expression significantly decreased cell viability, colony formation and cell migration ability in TNBC cells (P < 0.05). CONCLUSIONS: Evidence from observational studies and in vitro experiments indicates that LINC00449 and LINC01270 may be prognostic biomarkers for TNBC.

Road Traffic and Urban Form Factors Correlated with the Incidence of Lung Cancer in High-density Areas: An Ecological Study in Downtown Shanghai, China.

The incidence of lung cancer is affected by air pollution, especially in high-density urban areas with heavy road traffic and dense urban form. Several studies have examined the direct relationship between lung cancer incidence and road traffic as well as urban form. However, the results are still inconsistent for high-density urban areas. This study focused on urban form and road traffic, aiming at revealing their relationship with lung cancer incidence in high-density urban areas at the neighborhood level. For this, an ecological study was conducted in downtown Shanghai to identify important indicators and explore quantitative associations. Negative binomial regression was fitted with lung cancer incidence as the dependent variable. The independent variables included indicators for road traffic and urban form, greenness, demographic, and socio-economic factors. The results showed that building coverage, averaged block perimeter area ratio, density of metro station without the glass barrier system, and the percentage of low-quality residential land were positively correlated with lung cancer incidence in the neighborhood, while population density was negatively correlated with lung cancer incidence. This study found a strong self-selection effect of socio-economic factors in the relationship between lung cancer incidence and greenness. These results may be useful for conducting health impact assessments and developing spatial planning interventions for respiratory health in high-density urban areas.

Increasing Gap Between Thyroid Cancer Incidence and Mortality in Urban Shanghai, China: An Analysis Spanning 43 Years.

OBJECTIVE: To examine the secular trends of thyroid cancer incidence and mortality and to estimate the proportion of thyroid cancer cases potentially attributable to overdiagnosis. METHODS: Data on thyroid cancer cases from 1973 to 2015 were obtained from the Shanghai Cancer Registry. The average annual percent change (AAPC) was evaluated using the joinpoint regression analysis. The age, period, and birth cohort effects were assessed using an age-period-cohort model. The overdiagnosis of thyroid cancer cases was estimated based on the difference between observed and expected incidences using the rates of Nordic countries as reference. RESULTS: From 1973 to 2015, the number of thyroid cancer cases was 23 117, and 75% of the patients were women. The age-standardized rates were seven- to eightfold higher from 2013 to 2015 than from 1973 to 1977. Compared with relatively stable mortality, thyroid cancer incidence was dramatically increased from 2002 to 2015 in both sexes, with significant trends (men: AAPC = 21.84%, 95% CI: 18.77%-24.98%, P < .001; women: AAPC = 18.55%, 95% CI: 16.49%-20.64%, P < .001). The proportion of overdiagnosis has gradually increased over time, rising from 68% between 2003 and 2007 to more than 90% between 2013 and 2015. This increasing trend appeared to be similar between men and women. CONCLUSION: An increasing gap between thyroid cancer incidence and mortality was observed in Shanghai, and overdiagnosis has contributed substantially to the rise of incidence, which calls for an urgent update on the practice of thyroid examination.

Accelerated aging in breast cancer survivors and its association with mortality and cancer recurrence.

PURPOSE: To prospectively investigate accelerated aging and its association with total mortality and breast cancer-specific mortality/recurrence among breast cancer survivors. METHODS: This study included 4218 female breast cancer patients enrolled into a population-based cohort study approximately 6-month post-diagnosis. Information on aging-related symptoms (i.e., self-rated overall health condition, energy level, depression, sleep difficulty, and quality) was collected at 18- and 36-month post-diagnosis surveys. Information on overall health, daily function impairments, survival status, and recurrence was collected at 10-year post-diagnosis survey. Record linkages with vital statistics were conducted to collect mortality information. Cox proportional hazards model was applied. RESULTS: Among 3041 10-year survivors with a mean age of 63.7 ± 9.7 years, respectively, 52.3%, 19.0%, and 27.6% reported poor health, limitation in daily activity, and climbing floors. Age-specific prevalence revealed that breast cancer survivors reached similar prevalence of the functional limitations 5-10 years earlier than cancer-free women. At the 18-month post-diagnosis survey, respectively, 47.0%, 72.5%, and 25.1% of survivors reported unsatisfied overall health condition, reduced energy level, and depression symptoms. After a median follow-up of 10.9 years, low self-rated overall health, low energy level, and depression were significantly associated with increased total mortality, with hazard ratios (HRs; 95% confidence intervals [CI]) of 3.14 (2.43, 4.06), 1.49 (1.20, 1.84), and 1.59 (1.21, 2.09), respectively. Low self-rated health was associated with breast cancer-specific mortality/recurrence (HR 1.85, 95% CI 1.30, 2.65). No significant association was found for sleep difficulty and quality. CONCLUSION: Aging-related physical changes/symptoms are commonly presented at 18 months after breast cancer diagnosis and are associated with worse prognosis. IMPACT: Our findings highlight the concern of accelerated aging among breast cancer survivors.

Physically active individuals have a 23% lower risk of any colorectal neoplasia and a 27% lower risk of advanced colorectal neoplasia than their non-active counterparts: systematic review and meta-analysis of observational studies.

BACKGROUND: Few studies have examined the associations between physical activity (PA), sedentary behaviour (SB) and risk of colorectal neoplasia (CN). METHODS: We systematically searched Medline, Embase, PsyInfo, Cochrane and other sources from their inception to 30 September 2018 for cohort, case-control and cross-sectional studies that evaluated these associations in asymptomatic, average-risk subjects. Random-effect models were used to estimate relative risks (RRs) of any-type CN, advanced CN, and non-advanced CN, respectively, in individuals with the highest versus the lowest level of PA and SB. Dose-response analyses and subgroup analyses were conducted. The I2 statistic was used to examine heterogeneity among studies. RESULTS: We identified 32 observational studies, including 17 cross-sectional studies, 10 case-control studies and five longitudinal studies. PA (highest vs lowest) was inversely associated with risk for any-type CN (n=23 studies) and advanced CN (n=15 studies), with a RR of 0.77 (95% CI=0.71 to 0.83, I2=57.5%) and 0.73 (95% CI=0.63 to 0.82, I2=45.5%), respectively. There was no association between PA and non-advanced CN (n=5 studies). There was an as association between PA and any-type CN in both sexes, and also for the distal colon. We found no dose-response relationship between PA and any-type or advanced CN. Based on three studies identified, SB time (longest vs shortest) was associated with an increased risk of advanced CN (RR=1.24, 95% CI 1.04 to 1.49, I2=14.4%). No publication bias was detected by Begg's test. CONCLUSION: We report a 23% lower relative risk of any type of CN and a 27% lower risk of advanced CN in people with the highest level of PA compared with those in the lowest.

The performance of a community-based colorectal cancer screening program: Evidence from Shanghai Pudong New Area, China.

Despite the rising disease burden of colorectal cancer (CRC), CRC screening has not yet been widely introduced as a large organized program in developing countries. To facilitate better delivery of screening in these areas, we investigated the performance of a large community-based CRC screening program implemented in Shanghai Pudong New Area during the period 2013-2016. We conducted a prospective cohort study by following up the screening behavior and results of tested participants in the program. Data from the program reporting system and monthly progress reports were collected. We used standard measures and indicators with modifications to evaluate the performance of the program. Disparities in CRC screening by age categories, primary screening results, and geographic areas were examined. A total of 403,098 individuals participated in the program, 25,764 of them were further screened by diagnostic colonoscopy (COL), and 505 people were eventually diagnosed with CRC as a result of the program. The program produced the following rates: participation (35.18%), primary screening positivity (24.89%), positive primary screening follow-up (26.26%), diagnostic COL (6.37%), and cancer detection (1.25‰). Vast variations in the quality of the program were observed across areas with different socioeconomic environments. The experience and lessons from the program suggest that incorporating the screening with other public health campaigns, using better-developed risk assessment tools, and allowing individual screening decisions for those aged above the target are possible practical ways to promote a better delivery of organized CRC screening programs.

The Implementation and First-Round Results of a Community-Based Colorectal Cancer Screening Program in Shanghai, China.

BACKGROUND: The incidence and mortality rate of colorectal cancer (CRC) have increased dramatically over the past 3 decades in China due to changes in lifestyle factors. Early detection and treatment guidelines for asymptomatic cases have shown to improve CRC control in developed countries. In response to these challenges, the Shanghai Municipal Government launched a community-based CRC screening program in 2012. MATERIALS AND METHODS: Free initial screening, inclusive of immunochemical fecal occult blood and risk assessment (questionnaire), was provided by community health centers in Shanghai. Participants with positive results were referred to a specialist for a colonoscopy. RESULTS: In 2013, 828,302 Shanghai residents were registered; 97.7% (809,528) of the registrants completed initial screening. Among 180,094 initial screening-positive participants, 71,733 underwent colonoscopy. The proportion of compliance to colonoscopy was 39.8%; the proportion decreased with age and educational level. A total of 6,668 adenomas were detected, and 1,630 CRC cases were diagnosed. The CRC detection rate of the program was 201.35/100,000; among the detected CRCs, 51.6% were in stage 0-I. CONCLUSION: The screening program achieved great progress, especially on initial screening completion and CRC early stage rate, although particular intervention is still needed to improve the compliance of colonoscopy. IMPLICATIONS FOR PRACTICE: Due to socioeconomic transitions and lifestyle changes, colorectal cancer is now becoming one of the most common cancers in developing countries, as it is in developed countries. While most developed countries have now initiated national colorectal cancer screening programs based on recommended country-specific colorectal cancer screening guidelines, colonoscopy has become the most commonly used screening method. This is a challenge in developing countries due to limited resources. Based on the analysis of the Shanghai colorectal cancer screening program, with immunological fecal occult blood test and risk assessment as initial screening, followed by a diagnostic testing of colonoscopy for individuals with positive results, this article provides the basis and suggestion for similar program in other regions of China and other developing countries.

Associations of dietary intake and supplement use with post-therapy cognitive recovery in breast cancer survivors.

PURPOSE: Cognitive impairment induced by cancer therapy is common and can be long lasting after completion of therapy. Little is known on factors that influence recovery from the impairment. We evaluated the associations of dietary intake and supplement use with post-therapy cognitive recovery in a large cohort of breast cancer survivors. METHODS: This study included 1047 breast cancer patients aged 20-75 who were recruited to the Shanghai Breast Cancer Survival Study between 2002 and 2006 at approximately 6.5 months post-cancer diagnosis. Two cognitive assessments covering immediate memory, delayed memory, verbal fluency, and attention, were conducted at 18 and 36 months post-diagnosis. We used food frequency questionnaire to collect information on their dietary intake and supplement use between 18 and 36 months post-diagnosis. Linear regression models were used to examine the associations of dietary intake and supplement use with mean cognitive scores at 36 months post-diagnosis and with differences in cognitive scores between 18 and 36 months post-diagnosis. RESULTS: Higher vegetable, fruit and fish intake, supplementation with vitamin B and vitamin E, and tea drinking were associated with higher cognitive scores, while alcohol drinking was associated with lower cognitive scores at 36 months post-diagnosis. Vegetable intake was positively associated with improvement in verbal fluency, while tea drinking and fish oil supplementation were associated with greater improvements in delayed memory between 18 and 36 months post-diagnosis. CONCLUSIONS: Our results indicate that higher vegetable intake, tea drinking, and fish oil supplementation may help post-therapy cognitive recovery for cancer patients.

Gene expression in triple-negative breast cancer in relation to survival.

PURPOSE: The identification of biomarkers related to the prognosis of triple-negative breast cancer (TNBC) is critically important for improved understanding of the biology that drives TNBC progression. METHODS: We evaluated gene expression in total RNA isolated from formalin-fixed paraffin-embedded tumor samples using the NanoString nCounter assay for 469 TNBC cases from the Shanghai Breast Cancer Survival Study. We used Cox regression to quantify Hazard Ratios (HR) and corresponding confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS) in models that included adjustment for breast cancer intrinsic subtype. Of 302 genes in our discovery analysis, 22 were further evaluated in relation to OS among 134 TNBC cases from the Nashville Breast Health Study and the Southern Community Cohort Study; 16 genes were further evaluated in relation to DFS in 335 TNBC cases from four gene expression omnibus datasets. Fixed-effect meta-analysis was used to combine results across data sources. RESULTS: Twofold higher expression of EOMES (HR 0.90, 95% CI 0.83-0.97), RASGRP1 (HR 0.89, 95% CI 0.82-0.97), and SOD2 (HR 0.80, 95% CI 0.66-0.96) was associated with better OS. Twofold higher expression of EOMES (HR 0.89, 95% CI 0.81-0.97) and RASGRP1 (HR 0.87, 95% CI 0.81-0.95) was also associated with better DFS. On the contrary, a doubling of FA2H (HR 1.14, 95% CI 1.06-1.22) and GSPT1 (HR 1.33, 95% CI 1.14-1.55) expression was associated with shorter DFS. CONCLUSIONS: We identified five genes (EOMES, FA2H, GSPT1, RASGRP1, and SOD2) that may serve as potential prognostic biomarkers and/or therapeutic targets for TNBC.

Long-term soy consumption and tumor tissue MicroRNA and gene expression in triple-negative breast cancer.

BACKGROUND: Soy food intake may have protective effects against the risk for breast cancer, including estrogen receptor (ER)-negative breast cancer. However, the underlying molecular mechanisms remain unclear. METHODS: To evaluate the association of soy intake with the expression of microRNAs (miRNAs) and genes in the tumor tissue of patients with triple-negative breast cancer (TNBC; ie, breast cancer lacking expression of ER, progesterone receptor, and human epidermal growth factor receptor 2), the expression of 800 miRNAs and 302 genes were measured with NanoString nCounter assays in formalin-fixed, paraffin-embedded tumor tissue from 272 TNBC patients. Soy intake during the 1-year period before the cancer diagnosis was assessed with a validated food-frequency questionnaire. The association of soy intake with the expression of miRNAs and genes was evaluated via linear regression analysis with adjustments for patient age and TNM stage. RESULTS: A total of 14 miRNAs and 24 genes were significantly associated with soy food intake (P < .05): Thirteen of the 14 miRNAs (92.9%) and 9 of the 24 genes (37.5%), including tumor suppressors miR-29a-3p and IGF1R, showed overexpression for those women with high soy intake, whereas the remaining miRNAs and genes, including oncogenes KRAS and FGFR4, showed underexpression. Furthermore, cell growth-related genes showed a predominantly underexpression pattern according to a comparison of tumor samples from women with high soy food intake and samples from women with lower soy food intake. CONCLUSIONS: This study suggests that long-term prediagnosis soy intake may lead to increased expression of tumor suppressors and decreased expression of oncogenes, especially cell growth-related genes, in breast tumor tissues. Cancer 2016;122:2544-51. © 2016 American Cancer Society.

Body mass index and weight change in relation to triple-negative breast cancer survival.

The aim of this study was to evaluate the influence of body mass index (BMI), weight change on triple-negative breast cancer (TNBC) prognosis in a population-based prospective cohort study. The current analysis included 518 participants diagnosed with TNBC in Shanghai Breast Cancer Survival Study. Weight at 1 year prior to cancer diagnosis, at diagnosis, and at 6, 18 and 36 months after cancer diagnosis and height at 6 months after cancer diagnosis were assessed. Disease-free survival (DFS) and overall survival (OS) were evaluated in relation to BMI and weight change using Cox proportional hazard models. Obesity (BMI ≥ 28.0 kg/m(2)) at 1-year pre-diagnosis was associated with higher risk of total mortality and recurrence/disease-specific mortality, with multivariate hazard ratios (HRs) of 1.79 (95 % CI 1.06-3.03) and 1.83 (95 % CI 1.05-3.21), respectively. The associations between BMI and TNBC prognosis attenuated over time from pre-diagnosis to post-diagnosis. Compared with stable weight (change within 5 %), weight loss ≥5 % at 18- or 36-month post-diagnosis was related with higher risk of total mortality and recurrence/disease-specific mortality. Respective multivariate HRs were 2.08 (95 % CI 1.25-3.46) and 1.42 (95 % CI 0.77-2.63) for OS, and 2.50 (95 % CI 1.45-4.30) and 2.17 (95 % CI 1.14-4.12) for DFS. However, the association of weight loss and OS/DFS attenuated after excluding patients whose weight was measured after recurrence. Weight gain ≥5 % at 18- or 36-month post-diagnosis was associated with a non-significant increased risk of death. The results showed that obesity pre-diagnosis and weight loss post-diagnosis was inversely associated with TNBC prognosis. Emphasis on maintaining stable weight after cancer diagnosis for TNBC patients may be considered.

Cancer incidence in urban Shanghai, 1973-2010: an updated trend and age-period-cohort effects.

BACKGROUND: To provide a comprehensive overview of temporal trends in cancer incidence during 1973-2010 in urban Shanghai. METHODS: The estimated annual percent changes (EAPCs) for the whole period and for the time segments in age-standardized incidence rates (ASR) were evaluated with Joinpoint analysis. Age-period-cohort (APC) models were modeled to examine the effects of age, period and birth cohort on cancer incidence. RESULTS: The overall ASR decreased slightly and significantly in males (EAPC of -0.41) but increased significantly in females (EAPC of 0.57) during 1973-2010 in urban Shanghai. The incidence trend was not linear and varied by time segments. During the most recent 10 years (2001-2010), the ASR in males decreased by 1.65% per year and stabilized in females. Incidence rates continued to decline during 1973-2010 for esophagus, stomach, and liver cancer in both sexes, as well as male lung cancer and cervix cancer. It should be noted that it was the first time to document a significant decline in lung cancer incidence among males during 1973-2010 with EAPC of -0.58%, and a notable upward for cervix cancer since 1996 with EAPC of 8.94%. Unfavorable trends in incidence were observed for the most common cancer sites in the 38 years period: colorectum, gallbladder & biliary tract, pancreas, kidney, bladder, brain & central nervous system (CNS), thyroid, non-Hodgkin's lymphoma (NHL), prostate, female breast, corpus uteri, and ovary. APC analysis showed age, period and birth cohort yielded different effects by cancer sites. CONCLUSIONS: The observed trends primarily reflect dramatic changes in socioeconomic development and lifestyles in urban Shanghai over the past four decades.

Tumor tissue microRNA expression in association with triple-negative breast cancer outcomes.

We evaluated suggested metastasis-related microRNAs (miRNAs) for their associations with disease-free survival (DFS) and overall survival (OS) of triple-negative breast cancer (TNBC). In a cohort of 456 TNBC cases, we systematically evaluated 57 previously reported metastasis-related miRNAs in tumor tissue using the NanoString nCounter assay. Cox regression was applied to evaluate miRNA expression in association with DFS and OS. In vitro assays using the TNBC cell line MDA-MB-231 were also conducted to validate epidemiological study findings. During a median follow-up of 5.3 years, 112 deaths and 97 recurrences were documented. High levels of miR-374b-5p, miR-218-5p, or miR-126-3p, or low levels of miR-27b-3p were independently associated with a favorable TNBC outcome (P < 0.01 for all). A composite score based on the levels of these four miRNAs was associated with DFS, with hazard ratios (95 % confidence interval) of 0.70 (0.43-1.15), 0.51 (0.29-0.90), and 0.18 (0.09-0.37) for the second, third, and fourth compared to the lowest quartile. Incorporating the miRNA score with known TNBC outcome predictors, i.e., age at diagnosis, tumor stage, and basal-like subtype, increased the C-index for predicting DFS from 0.68 to 0.74. Additionally, miR-126-3p was correlated with basal-like breast cancer, and miR-374b-5p modified the therapeutic effects of 5-Fluorouracil and Cyclophosphamide treatments in basal-like breast cancer patients. Restoring miR-126-3p, miR-218-5p, or miR-374b-5p, or inhibiting miR-27b-3p in MDA-MB-231 cells reduced cell proliferation. miR-374b-5p suppressed cell invasion and miR-218-5p inhibited colonization. This study provides strong evidence that the expression levels of miR-374b-5p, miR-27b-3p, miR-126-3p, and miR-218-5p in tumor tissues predict TNBC outcomes.