High expression of cyclin D1 is associated to high proliferation rate and increased risk of mortality in women with ER-positive but not in ER-negative breast cancers

Purpose

Cyclin D1 has a central role in cell cycle control and is an important component of estrogen regulation of cell cycle progression. We have previously shown that high cyclin D expression is related to aggressive features of ER-positive but not ER-negative breast cancer. The aims of the present study were to validate this differential ER-related effect and furthermore explore the relationship between cyclin D overexpression and CCND1 gene amplification status in a node-negative breast cancer case–control study.

Methods

Immunohistochemical nuclear expression of cyclin D1 (n = 364) and amplification of the gene CCND1 by fluorescent in situ hybridization (n = 255) was performed on tissue microarray sections from patients with T1-2N0M0 breast cancer. Patients given adjuvant chemotherapy were excluded. The primary event was defined as breast cancer death. Breast cancer-specific survival was analyzed in univariate and multivariable models using conditional logistic regression.

Results

Expression of cyclin D1 above the median (61.7%) in ER breast cancer was associated with an increased risk for breast cancer death (OR 3.2 95% CI 1.5–6.8) also when adjusted for tumor size and grade (OR 3.1). No significant prognostic impact of cyclin D1 expression was found among ER-negative cases. Cyclin D1 overexpression was significantly associated to high expression of the proliferation markers cyclins A (ρ 0.19, p = 0.006) and B (ρ 0.18, p = 0.003) in ER-positive tumors, but not in ER-negative cases. There was a significant association between CCND1 amplification and cyclin D1 expression (p = 0.003), but CCND1 amplification was not statistically significantly prognostic (HR 1.4, 95% CI 0.4–4.4).

Conclusion

We confirmed our previous observation that high cyclin D1 expression is associated to high proliferation and a threefold higher risk of death from breast cancer in ER-positive breast cancer.

     

Application of Rasch Analysis to Examine Psychometric Aspects of the Activities-Specific Balance Confidence Scale When Used in a New Cultural Context

Arnadottir SA, Lundin-Olsson L, Gunnarsdottir ED, Fisher AG. Application of Rasch analysis to examine psychometric aspects of the Activities-Specific Balance Confidence Scale when used in a new cultural context.

Objective

To investigate by using Rasch analysis the psychometric properties of the Activities-Specific Balance Confidence (ABC) Scale when applied in a new Icelandic context.

Design

Cross-sectional, population-based, random selection from the Icelandic National Registry.

Setting

Community-based.

Participants

Icelanders (N=183), 65 to 88 years old, and 48% women.

Interventions

Not applicable.

Main Outcome Measure

ABC, an instrument used to evaluate how confident older people are in maintaining balance and remaining steady when moving through the environment. An Icelandic translation of the ABC (ABC-ICE) scale was evaluated by implementing Rasch rating scale analysis to transform ordinal ABC-ICE scores into interval measures and evaluating aspects of validity and reliability of the scale.

Results

Participants were not able to differentiate reliably between the 11 rating scale categories of the ABC-ICE. Additionally, 3 items failed to show acceptable goodness of fit to the ABC-ICE rating scale model. By collapsing categories and creating a new 5-category scale, only 1 item misfit. Removing that item resulted in a modified version of ABC-ICE with 5 categories and 15 items. Both item goodness-of-fit statistics and principal components analysis supported unidimensionality of the modified ABC-ICE. The ABC-ICE measures reliably separated the sample into at least 4 statistically distinct strata of balance confidence. Finally, the hierarchical order of item difficulties was consistent with theoretic expectations, and the items were reasonably well targeted to the balance confidence of the persons tested.

Conclusions

Rasch analysis indicated a need to modify the ABC-ICE to improve its psychometric properties. Further studies are needed to determine if similar analyses of other versions of the ABC, including the original one, will yield similar results.     

Quality of Life and its Relation to Cancer-Related Stress in Women of Families with Hereditary Cancer without Demonstrated Mutation

Background: Although quality of life (QoL) and mental distress in women belonging to familial cancer families have been studied, little is known on these matters in women with absence of demonstrated mutations. The aim of this study was to examine QoL and cancer-related distress in such women. Methods: About 330 women at risk for familial cancers in the absence of demonstrated mutations were invited to the study. About 239 women (72%) (risk group) completed the Short Form 12 (SF-12) and the Impact of Event Scale (IES). The SF-12-findings were compared to the age-adjusted findings from the general female population (controls). Results: The risk group had significantly better physical QoL than controls, while no significant difference was found for mental QoL. Within the risk group the type of familial cancer did not make a significant difference in QoL, but to have a father with cancer or a deceased parent, was associated with increased risk of being a case with low QoL. Mental QoL showed moderate correlation with cancer-related distress. Conclusions: : Women belonging to familial cancer families in the absence of demonstrated mutations had at least as good QoL as controls in spite of living with a permanent cancer-related threat.     

Children’s Participation in Free School Meals: A Qualitative Study among Pupils,Parents, and Teachers

School meals can have a key function in promoting children’s health. However, simply providing a free school meal is not a guarantee that pupils will eat the food. The purpose of this study was to explore factors influencing pupils’ participation in free school meal schemes in Oslo. The study has a qualitative research design, inspired by grounded theory. Data were collected through interviews with pupils, teachers, and parents, and participant observations in two schools participating in a pilot project funded by Oslo Municipality. Line-by-line coding, memo writing, and a constant comparative technique were used to analyze the data. One primary school and one lower-secondary school in different districts in Oslo that were implementing two different free school meal models took part in the study. In total, 39 pupils (5th–10th grade), 15 parents, and 12 school employees were included. Four main factors related to pupils’ participation in free school meals emerged from the analysis: the popularity of the food served, the attraction to the nearby shopping center, social aspects, and predictability. To promote pupils’ participation in free school meal schemes, schools need to solve the challenges of balancing between healthy food and popular but often unhealthy food. To implement school meals further, children and parents’ involvement, regularity of the meals provision, a good flow of information, and the creation of a friendly eating environment are recommended.     

Assessing PDL-1 and PD-1 in Non–Small Cell Lung Cancer: A Novel Immunoscore Approach

Introduction

Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand, PD-L1, have gained momentum in the treatment of non–small cell lung cancer (NSCLC). However, their prognostic significance remains controversial. The present study evaluated the expression of PD-L1 and PD-1 and their potential role in an Immunoscore, supplementing the TNM classification of NSCLC.

Weak mathematical skills at an early age: persistent or temporary? Children with weak mathematical skills and their development from toddlers to preschoolers

The aim of the study is to examine how toddlers (33 months) with weak mathematical skills differ from their peers, the extent to which those weak skills persist into preschool age (57 months), and how the group with persisting weak skills differs from the group with temporary weak skills. Participants were 692 children (344 girls, 348 boys). The children were observed during play and daily-life activities over two three-month periods to make an authentic assessment of a wide area of mathematical skills. The toddlers with weak skills had weaker skills than their peers in all parts of mathematics. The largest difference was in the numerical areas. Only 25% had persistent weak skills into preschool age. No difference in mathematical skills was found between the persistently weak group and the temporarily weak group at toddler age. The findings indicate that predicting weak development in toddlers is difficult.