Modern mammography screening and breast cancer mortality: population study

Objective: To evaluate the effectiveness of contemporary mammography screening using individual information about screening history and breast cancer mortality from public screening programmes. Design: Prospective cohort study of Norwegian women who were followed between 1986 and 2009. Within that period (1995-2005), a national mammography screening programme was gradually implemented, with biennial invitations sent to women aged 50-69 years. Participants: All Norwegian women aged 50-79 between 1986 and 2009. Main outcome measures Multiple Poisson regression analysis was used to estimate breast cancer mortality rate ratios comparing women who were invited to screening (intention to screen) with women who were not invited, with a clear distinction between cases of breast cancer diagnosed before (without potential for screening effect) and after (with potential for screening effect) the first invitation for screening. We took competing causes of death into account by censoring women from further follow-up who died from other causes. Based on the observed mortality reduction combined with the all cause and breast cancer specific mortality in Norway in 2009, we used the CISNET (Cancer Intervention and Surveillance Modeling Network) Stanford simulation model to estimate how many women would need to be invited to biennial mammography screening in the age group 50-69 years to prevent one breast cancer death during their lifetime. Results: During 15 193 034 person years of observation (1986-2009), deaths from breast cancer occurred in 1175 women with a diagnosis after being invited to screening and 8996 women who had not been invited before diagnosis. After adjustment for age, birth cohort, county of residence, and national trends in deaths from breast cancer, the mortality rate ratio associated with being invited to mammography screening was 0.72 (95% confidence interval 0.64 to 0.79). To prevent one death from breast cancer, 368 (95% confidence interval 266 to 508) women would need to be invited to screening. Conclusion: Invitation to modern mammography screening may reduce deaths from breast cancer by about 28%

Pre-eclampsia, Soluble fms-like Tyrosine Kinase 1, and the Risk of Reduced Thyroid Function: Nested Case-Control and Population Based Study

Objective: To determine if pre-eclampsia is associated with reduced thyroid function during and after pregnancy. Design: Nested case-control study during pregnancy and population based follow-up study after pregnancy. Setting: Calcium for Pre-eclampsia Prevention trial of healthy pregnant nulliparous women in the United States during 1992-5, and a Norwegian population based study (Nord-Trondelag Health Study or HUNT-2) during 1995-7 with linkage to the medical birth registry of Norway. Participants: All 141 women (cases) in the Calcium for Pre-eclampsia Prevention trial with serum measurements before 21 weeks’ gestation (baseline) and after onset of pre-eclampsia (before delivery), 141 normotensive controls with serum measurements at similar gestational ages, and 7121 women in the Nord-Trondelag Health Study whose first birth had occurred in 1967 or later and in whom serum levels of thyroid stimulating hormone had been subsequently measured. Main outcome measures: Thyroid function tests and human chorionic gonadotrophin and soluble fms-like tyrosine kinase 1 concentrations in the Calcium for Pre-eclampsia Prevention cohort and odds ratios for levels of thyroid stimulating hormone above the reference range, according to pre-eclampsia status in singleton pregnancies before the Nord-Trondelag Health Study. Results: In predelivery specimens of the Calcium for Pre-eclampsia Prevention cohort after the onset of pre-eclampsia, thyroid stimulating hormone levels increased 2.42 times above baseline compared with a 1.48 times increase in controls. The ratio of the predelivery to baseline ratio of cases to that of the controls was 1.64 (95% confidence interval 1.29 to 2.08). Free triiodothyronine decreased more in the women with pre-eclampsia than in the controls (case ratio to control ratio 0.96, 95% confidence interval 0.92 to 0.99). The predelivery specimens but not baseline samples from women with pre-eclampsia were significantly more likely than those from controls to have concentrations of thyroid stimulating hormone above the reference range (adjusted odds ratio 2.2, 95% confidence interval 1.1 to 4.4). Both in women who developed pre-eclampsia and in normotensive controls the increase in thyroid stimulating hormone concentration between baseline and predelivery specimens was strongly associated with increasing quarters of predelivery soluble fms-like tyrosine kinase 1 (P for trend 0.002 and 3.5 mIU/l). In particular, they were more likely to have high concentrations of thyroid stimulating hormone without thyroid peroxidase antibodies (adjusted odds ratio 2.6, 95% confidence interval 1.3 to 5.0), suggesting hypothyroid function in the absence of an autoimmune process. This association was especially strong (5.8, 1.3 to 25.5) if pre-eclampsia had occurred in both the first and the second pregnancies. Conclusion: Increased serum concentration of soluble fms-like tyrosine kinase 1 during pre-eclampsia is associated with subclinical hypothyroidism during pregnancy. Pre-eclampsia may also predispose to reduced thyroid function in later years

School wellbeing among children in grades 1-10

Background: Determinants of children’s school wellbeing have not been extensively studied. In this cross-sectional study of school children we assessed how factors assumed to promote wellbeing and factors assumed to adversely influence wellbeing were associated with self-reported wellbeing in school. Methods: Children from five schools, 230 boys and 189 girls in grades 1-10, responded to the same set of questions. We used proportional odds logistic regression to assess the associations of promoting and restraining factors with school wellbeing. Results: In a multivariable analysis, degree of school wellbeing in boys was strongly and positively related to enjoying school work (odds ratio, 3.84, 95% CI 2.38 to 6.22) and receiving necessary help (odds ratio, 3.55, 95% CI 2.17 to 5.80) from teachers. In girls, being bothered during lessons was strongly and negatively associated with school wellbeing (odds ratio, 0.43, 95% CI 0.22 to 0.85). Conclusions: Different factors may determine school wellbeing in boys and girls, but for both genders, factors relevant for lessons may be more important than factors related to recess. Especially in boys, the student-teacher relationship may be of particular importance.© 2010 Løhre et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Breast cancer mortality in neighbouring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database

Objective To compare trends in breast cancer mortality within three pairs of neighbouring European countries in relation to implementation of screening

Understanding recent trends in incidence of invasive breast cancer in Norway: age-period-cohort analysis based on registry data on mammography screening and hormone treatment use

Objective To quantify the separate contributions of menopausal hormone treatment and mammography screening activities on trends in incidence of invasive breast cancer between 1987 and 2008

Non-progressive breast carcinomas detected at mammography screening: a population study

Background Some breast carcinomas detected at screening, especially ductal carcinoma in situ, may have limited potential for progression to symptomatic disease. To determine non-progression is a challenge, but if all screening-detected breast tumors eventually reach a clinical stage, the cumulative incidence at a reasonably high age would be similar for women with or without screening, conditional on the women being alive. Methods Using high-quality population data with 24 years of follow-up from the gradually introduced BreastScreen Norway program, we studied whether all breast carcinomas detected at mammography screening 50–69 years of age would progress to clinical symptoms within 85 years of age. First, we estimated the incidence rates of breast carcinomas by age in scenarios with or without screening, based on an extended age-period-cohort incidence model. Next, we estimated the frequency of non-progressive tumors among screening-detected cases, by calculating the difference in the cumulative rate of breast carcinomas between the screening and non-screening scenarios at 85 years of age. Results Among women who attended BreastScreen Norway from the age of 50 to 69 years, we estimated that 1.1% of the participants were diagnosed with a breast carcinoma without the potential to progress to symptomatic disease by 85 years of age. This proportion of potentially non-progressive tumors corresponded to 15.7% [95% CI 3.3, 27.1] of breast carcinomas detected at screening. Conclusions Our findings suggest that nearly one in six breast carcinomas detected at screening may be non-progressive.publishedVersio

Interpreting Breast Cancer Mortality Trends Related to Introduction of Mammography Screening: A Simulation Study

Background. Several studies have evaluated the effect of mammography screening on breast cancer mortality based on overall breast cancer mortality trends, with varied conclusions. The statistical power of such trend analyses is, however, not carefully studied. Methods. We estimated how the effect of screening on overall breast cancer mortality is likely to unfold. Because a screening effect is based on earlier treatment, screening can affect only new incident cases after screening introduction. To evaluate the likelihood of detecting screening effects on overall breast cancer mortality time trends, we calculated the statistical power of joinpoint regression analysis on breast cancer mortality trends around screening introduction using simulations. Results. We found that a very gradual increase in population-level screening effect is expected due to prescreening incident cases. Assuming 25% effectiveness of a biennial screening program in reducing breast cancer mortality among women 50 to 69 y of age, the expected reduction in overall breast cancer mortality was 3% after 2 y and reached a long-term effect of 18% after 20 y. In common settings, the statistical power to detect any screening effects using joinpoint regression analysis is very low (<50%), even in an artificial setting of constant risk of baseline breast cancer mortality over time. Conclusions. Population effects of screening on breast cancer mortality emerge very gradually and are expected to be considerably lower than the effects reported in trials excluding women diagnosed before screening. Studies of overall breast cancer mortality time trends have too low statistical power to reliably detect screening effects in most populations. Implications. Researchers and policy makers evaluating mammography screening should avoid using breast cancer mortality trend analysis that does not separate pre- and postscreening incident cases.publishedVersio

Microvascular proliferation in luminal Aand basal-like breast cancer subtypes

Aims: The aims of this study were to examine microvessel density (MVD), proliferating MVD (pMVD) and Vascular Proliferation Index (VPI) in basal-like phenotype (BP) and luminal A subtypes of breast cancer and to study their prognostic value. Methods: Dual-colour immunohistochemistry for von Willebrand factor and Ki67 was done on sections from 62 luminal A and 62 BP tumours matched for grade and selected from 909 breast cancers previously reclassified into molecular subtypes. Associations between MVD, pMVD and VPI, molecular subtypes and breast cancer prognosis were estimated using linear regression and survival analyses. Results: Both pMVD (difference 1.9 microvessels/mm2 (p=0.002)) and VPI (difference 1.7 percentage points (p=0.014)) were higher in BP tumours compared with luminal A. No clear difference between subtypes was found for MVD. However, only MVD was associated with prognosis. HR for breast cancer death for all cases was 1.10 (95% CI 1.02 to 1.18) per 10 vessels increase. Among luminal A tumours, HR was 1.22 per 10 vessels increase (p<0.001) and in BP it was 1.04 (p=0.37). Conclusions: High MVD was associated with poor prognosis in luminal A, but not in BP cancers. Vascular proliferation was higher in BP, indicating a more active angiogenesis than in luminal A tumours. The luminal A subgroup comprised mostly histopathological grade 3 cancers in this selected series, and further studies are needed to clarify whether MVD provides additional prognostic information for luminal A tumours irrespective of grade. This may contribute to stratification of this large group of patients and may aid in identifying tumours with a particularly good prognosis.acceptedVersio

Random error units, extension of a novel method to express random error in epidemiological studies

Currently used methods to express random error are often misinterpreted and consequently misused by biomedical researchers. Previously we proposed a simple approach to quantify the amount of random error in epidemiological studies using OR for binary exposures. Expressing random error with the number of random error units (REU) does not require solid background in statistics for a proper interpretation and cannot be misused for making oversimplistic interpretations relying on statistical significance. We now expand the use of REU to the most common measures of associations in epidemiology and to continuous variables, and we have developed a Stata program, which greatly facilitates the calculation of REU.publishedVersion© 2019 Janszky et al. This work is published and licensed by Dove Medical Press Limited. Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/)