Epirubicin With Cyclophosphamide Followed by Docetaxel With Trastuzumab and Bevacizumab as Neoadjuvant Therapy for HER2-Positive Locally Advanced Breast Cancer or as Adjuvant Therapy for HER2-Positive Pathologic Stage III Breast Cancer: A Phase II Trial of the NSABP Foundation Research Group, FB-5

Background The purpose of this study was to determine the cardiac safety and clinical activity of trastuzumab and bevacizumab with docetaxel after epirubicin with cyclophosphamide (EC) in patients with HER2-positive locally advanced breast cancer (LABC) or pathologic stage 3 breast cancer (PS3BC). Patients and Methods Patients received every 3 week treatment with 4 cycles of EC (90/600 mg/m2) followed by 4 cycles of docetaxel (100 mg/m2). Targeted therapy with standard-dose trastuzumab with bevacizumab 15 mg/kg was given for a total of 1 year. Coprimary end points were (1) rate of cardiac events (CEs) in all patients defined as clinical congestive heart failure with a significant decrease in left ventricular ejection fraction or cardiac deaths; and (2) pathologic complete response (pCR) in breast and nodes in the neoadjuvant cohort. An independent cardiac review panel determined whether criteria for a CE were met. Results A total of 105 patients were accrued, 76 with LABC treated with neoadjuvant therapy and 29 with PS3BC treated with adjuvant therapy. Median follow-up was 59.2 months. Among 99 evaluable patients for cardiac safety, 4 (4%; 95% confidence interval [CI], 1.1%-10.0%) met CE criteria. The pCR percentage in LABC patients was 46% (95% CI, 34%-59%). Five-year recurrence-free survival (RFS) and overall survival (OS) for all patients was 79.9% and 90.8%, respectively. Conclusion The regimen met predefined criteria for activity of interest with an acceptable rate of CEs. Although the pCR percentage was comparable with chemotherapy regimens with trastuzumab alone the high RFS and OS are of interest in these high-risk populations

HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer

Introduction: Recent data suggest that benefit from trastuzumab and chemotherapy might be related to expression of HER2 and estrogen receptor (ESR1). Therefore, we investigated HER2 and ESR1 mRNA levels in core biopsies of HER2-positive breast carcinomas from patients treated within the neoadjuvant GeparQuattro trial. Methods: HER2 levels were centrally analyzed by immunohistochemistry (IHC), silver in-situ hybridization (SISH) and qRT-PCR in 217 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) core biopsies. All tumors had been HER2-positive by local pathology and had been treated with neoadjuvant trastuzumab/ chemotherapy in GeparQuattro. Results: Only 73% of the tumors (158 of 217) were centrally HER2-positive (cHER2-positive) by IHC/SISH, with cHER2-positive tumors showing a significantly higher pCR rate (46.8% vs. 20.3%, p<0.0005). HER2 status by qRT-PCR showed a concordance of 88.5% with the central IHC/SISH status, with a low pCR rate in those tumors that were HER2-negative by mRNA analysis (21.1% vs. 49.6%, p<0.0005). The level of HER2 mRNA expression was linked to response rate in ESR1-positive tumors, but not in ESR1-negative tumors. HER2 mRNA expression was significantly associated with pCR in the HER2-positive/ESR1-positive tumors (p=0.004), but not in HER2-positive/ESR1-negative tumors. Conclusions: Only patients with cHER2-positive tumors - irrespective of the method used - have an increased pCR rate with trastuzumab plus chemotherapy. In patients with cHER2-negative tumors the pCR rate is comparable to the pCR rate in the non-trastuzumab treated HER-negative population. Response to trastuzumab is correlated to HER2 mRNA levels only in ESR1-positive tumors. This study adds further evidence to the different biology of both subsets within the HER2-positive group

Wage losses in the year after breast cancer: Extent and determinants among Canadian women

This article is available open access through the publisher’s website at the link below. © The Author 2008.Background - Wage losses after breast cancer may result in considerable financial burden. Their assessment is made more urgent because more women now participate in the workforce and because breast cancer is managed using multiple treatment modalities that could lead to long work absences. We evaluated wage losses, their determinants, and the associations between wage losses and changes for the worse in the family's financial situation among Canadian women over the first 12 months after diagnosis of early breast cancer. Methods - We conducted a prospective cohort study among women with breast cancer from eight hospitals throughout the province of Quebec. Information that permitted the calculation of wage losses and information on potential determinants of wage losses were collected by three pretested telephone interviews conducted over the year following the start of treatment. Information on medical characteristics was obtained from medical records. The main outcome was the proportion of annual wages lost because of breast cancer. Multivariable analysis of variance using the general linear model was used to identify personal, medical, and employment characteristics associated with the proportion of wages lost. All statistical tests were two-sided. Results - Among 962 eligible breast cancer patients, 800 completed all three interviews. Of these, 459 had a paying job during the month before diagnosis. On average, these working women lost 27% of their projected usual annual wages (median = 19%) after compensation received had been taken into account. Multivariable analysis showed that a higher percentage of lost wages was statistically significantly associated with a lower level of education (Ptrend = .0018), living 50 km or more from the hospital where surgery was performed (P = .070), lower social support (P = .012), having invasive disease (P = .086), receipt of chemotherapy (P < .001), self-employment (P < .001), shorter tenure in the job (Ptrend < .001), and part-time work (P < .001). Conclusion - Wage losses and their effects on financial situation constitute an important adverse consequence of breast cancer in Canada.The Canadian Breast Cancer Research Alliance, Canadian Institutes of Health Research, and Fondation de l’Université Laval

Constructing the digitalized sporting body: black and white masculinity in NBA/NHL internet memes

In this article, I examine the ways sport fans construct and circulate discourses of race and masculinity in cyberspace. I do this through an examination of a set of Internet memes that juxtapose the bodies of National Hockey League players with National Basketball Association players in one single image. I argue these memes celebrate White masculinity, while at the same time constructing African American athletes as individualistic, selfish, and unwilling to sacrifice their bodies for the greater good of the team. More so, I argue that these memes construct a form of racial ideology that is representative of White backlash politics

Hoop House Gardening in the Wapekeka First Nation as an Extension of Land-Based Food Practices

Rural Indigenous communities in Canada’s North face many challenges getting regular access to nutritious foods, primarily because of the high cost of market food, restricted availability of nutritious foods, and lack of government support for nutritious food programs. The consequences of food insecurity in this context are expressed in high rates of diabetes, heart disease, and childhood obesity. Many Indigenous communities are responding to issues related to healthy food access by attempting to rebuild local food capacity in their specific regions. Important first steps have been taken in developing local food initiatives, yet whether these initiatives are improving northern food security remains to be seen. We explore this question by working with the Oji-Cree First Nation in the community of Wapekeka, northern Ontario, to construct a hoop house and develop a school-based community gardening program. Using a community-based participatory approach, we determined that hoop house and gardening initiatives in rural, northern settings have the potential to build up local food production, develop the skills and knowledge of community members, engage youth in growing local food, and align with land-based food teachings. We show that despite widespread and multidimensional community hardships, there was considerable community buy-in and support for the project, which gives hope for future development and provides important insight for those seeking to initiate similar gardening, hoop house, or greenhouse initiatives in northern Indigenous communities.Les collectivités autochtones du Canada en milieu rural nordique ont de nombreux défis à relever pour avoir régulièrement accès à de la nourriture nutritive, principalement en raison du coût élevé des denrées alimentaires du marché, de la disponibilité restreinte d’aliments nutritifs et du manque de soutien gouvernemental pour l’adoption de programmes de provisions alimentaires nutritives. Dans ce contexte, les conséquences de l’insécurité alimentaire s’expriment par des taux élevés de diabète, de maladies du coeur et d’obésité infantile. De nombreuses collectivités autochtones relèvent les défis d’accès à des denrées saines en tentant de renforcer la capacité alimentaire locale de leurs propres régions. Ils ont déjà pris d’importantes mesures pour aboutir à des initiatives alimentaires locales, mais il reste à voir si ces initiatives permettent d’améliorer la sécurité alimentaire dans le Nord. Nous nous penchons sur cette question de concert avec la Première Nation oji-cri dans la collectivité de Wapekeka, dans le nord de l’Ontario, en construisant plus précisément une serre à arceaux et en aménageant un programme de jardinage scolaire. Grâce à notre approche participative et communautaire, nous avons déterminé que la serre à arceaux et les initiatives de jardinage en milieu rural nordique ont la possibilité de se traduire par l’accumulation d’aliments produits à l’échelle locale, de favoriser l’acquisition de compétences et de connaissances, d’inciter les jeunes à cultiver des aliments localement et de mettre en valeur les enseignements relatifs à la nourriture provenant de la terre. Nous montrons que malgré les difficultés multidimensionnelles répandues dans la collectivité, ce projet a suscité un appui considérable de la part des gens, ce qui donne de l’espoir en vue de développements futurs et permet aux personnes désirant mettre en oeuvre des initiatives semblables de jardinage, de serres à arceaux et de serres ordinaires dans les collectivités autochtones nordiques d’acquérir d’importantes connaissances

Are different reading problems associated with different anxiety types?

There is a reliable association between poor reading and anxiety, but we do not completely understand the specifics of this relationship. The current study included a sample of children (N = 284; Mage = 9.30, SDage = 1.31) who completed a reading (word, nonword, and text reading accuracy, word, nonword, and text reading fluency, passage reading comprehension) and anxiety (social anxiety, generalized anxiety, separation anxiety, physical injury fears/phobias, panic, obsessive compulsive symptoms) assessment. Analyses included bivariate and partial correlations, principal components analysis, and hierarchical clustering. We found a very tentative suggestion in the data that there may be a specific yet weak association between reading accuracy and social anxiety. The clinical implications and directions for future research are discussed

Crustal controls on light noble gas isotope variability along the andean volcanic arc

This study combines new noble gas data from fluid inclusions in minerals from Sabancaya, Ubinas, and El Misti (CVZ, Peru) and Villarica (South Chile, SVZ) with a revised noble gas compilation in the Andes, to identify systematic along arc variations in helium isotope compositions. We find 3He/4He ratios varying from 8.8 RA (Colombia) to 7.4 RA (Ecuador) within the NVZ, and only as high as 6.4 RA in the CVZ (RA is the atmospheric 3He/4He ratio of 1.39 × 10-6). These distinct isotope compositions cannot be explained by variable radiogenic 4He production via slab fluid transport of U and Th in the mantle wedge, since both NVZ and CVZ share similar slab sediment inputs (Th/La ≈ 0.08-0.13). Instead, the progressively more radiogenic 3He/4He signatures in Ecuador and Peru reflect 4He addition upon magma ascent/ storage in the crust, this being especially thick in Peru (&gt;70 km) and Ecuador (&gt;50 km) relative to Colombia (∼30-45 km). The intermediate compositions in the North (8.0 RA) and South (7.9 RA) Chile, both high sediment flux margins, mostly reflect a more efficient delivery of radiogenic He in the wedge from the subducted (U-Th-rich) terrigenous sediments. Our results bring strong evidence for the major role played by crustal processes in governing noble gas compositions along continental arcs

Reading and emotional-behavioural development in Finnish children : a longitudinal study of associations

Poor reading has been linked to negative outcomes on a wide range of emotional-behavioural dimensions in children. However, little is known about the time course of these associations. In this study we analyse data from a sample of Finnish children (N = 199; 106 boys) which included measures of reading fluency in grade 1 (age 7 or 8), and emotional (anxiety, depression, and somatization) and behavioural (adaptability, aggression, attention, atypicality, hyperactivity, social skills, and withdrawal) development at ages 4, 5, 6 (pre-school) and 9 (school-aged). In a series of stepwise regression models that controlled for non-verbal IQ and family risk for dyslexia, we tested if pre-school emotional-behavioural measures were associated with school-aged reading fluency, and whether school-aged reading fluency was associated with later emotional-behavioural development. We also tested if these associations were moderated by reported gender. Consistent with previous longitudinal studies, we found that poorer attention before school was associated with poorer reading in the early school years which in turn was associated with higher levels of anxiety and inattention in children in middle school. None of these associations were moderated by gender

Multi-stage genome-wide association study identifies new susceptibility locus for testicular germ cell tumour on chromosome 3q25

Recent genome-wide association studies (GWAS) and subsequent meta-analyses have identified over 25 SNPs at 18 loci, together accounting for >15% of the genetic susceptibility to testicular germ cell tumour (TGCT). To identify further common SNPs associated with TGCT, here we report a three-stage experiment, involving 4098 cases and 18 972 controls. Stage 1 comprised previously published GWAS analysis of 307 291 SNPs in 986 cases and 4946 controls. In Stage 2, we used previously published customised Illumina iSelect genotyping array (iCOGs) data across 694 SNPs in 1064 cases and 10 082 controls. Here, we report new genotyping of eight SNPs showing some evidence of association in combined analysis of Stage 1 and Stage 2 in an additional 2048 cases of TGCT and 3944 controls (Stage 3). Through fixed-effects meta-analysis across three stages, we identified a novel locus at 3q25.31 (rs1510272) demonstrating association with TGCT [per-allele odds ratio (OR) = 1.16, 95% confidence interval (CI) = 1.06-1.27; P = 1.2 × 10-9]

Obesity and Type 2 Diabetes Prevalence in Adults from Two Remote First Nations Communities in Northwestern Ontario, Canada

Objective. To assess the prevalence rates of obesity and type 2 diabetes in adults from two First Nations communities in northwestern Ontario, Canada. Methods. Body weight, height, and waist circumference as well as fasting and postprandial glucose levels following an oral glucose tolerance test were measured in 31 men and 41 women. Results. The mean age of the sample was 43 ± 13 y. The prevalence of obesity was 65.3% and was comparable between men and women. 90.3% of the individuals presented waist circumference levels greater than the thresholds associated with an increased risk of developing health problems. 26 of the 72 individuals (36.1%) were found to be type 2 diabetic. The prevalence of diabetes was not different between men and women. Conclusion. Using objective measurements, this study confirms that First Nations adults from remote communities of Canada continue to experience a disproportionately higher prevalence of obesity and type 2 diabetes than nonaboriginal Canadians