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

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%

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

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

High volumes of recent surgical admissions, time to surgery, and 60-day mortality

Aims: Few studies have investigated potential consequences of strained surgical resources. The aim of this cohort study was to assess whether a high proportion of concurrent acute surgical admissions, tying up hospital surgical capacity, may lead to delayed surgery and affect mortality for hip fracture patients. Methods: This study investigated time to surgery and 60-day post-admission death of patients 70 years and older admitted for acute hip fracture surgery in Norway between 2008 and 2016. The proportion of hospital capacity being occupied by newly admitted surgical patients was used as the exposure. Hip fracture patients admitted during periods of high proportion of recent admissions were compared with hip fracture patients admitted at the same hospital during the same month, on similar weekdays, and times of the day with fewer admissions. Results: Among 60,072 patients, mean age was 84.6 years (SD 6.8), 78% were females, and median time to surgery was 20 hours (IQR 11 to 29). Overall, 14% (8,464) were dead 60 days after admission. A high (75th percentile) proportion of recent surgical admission compared to a low (25th percentile) proportion resulted in 20% longer time to surgery (95% confidence interval (CI) 16 to 25) and 20% higher 60-day mortality (hazard ratio 1.2, 95% CI 1.1 to 1.4). Conclusion: A high volume of recently admitted acute surgical patients, indicating probable competition for surgical resources, was associated with delayed surgery and increased 60-day mortality.publishedVersio

Hospitals' discharge tendency and risk of death - An analysis of 60,000 Norwegian hip fracture patients

Purpose: A reduction in the length of hospital stay may threaten patient safety. This study aimed to estimate the effect of organizational pressure to discharge on 60-day mortality among hip fracture patients. Patients and Methods: In this cohort study, hip fracture patients were analyzed as if they were enrolled in a sequence of trials for discharge. A hospital’s discharge tendency was defined as the proportion of patients with other acute conditions who were discharged on a given day. Because the hospital’s tendency to discharge would affect hip fracture patients in an essentially random manner, this exposure could be regarded as analogous to being randomized to treatment in a clinical trial. The study population consisted of 59,971 Norwegian patients with hip fractures, hospitalized between 2008 and 2016, aged 70 years and older. To calculate the hospital discharge tendency for a given day, we used data from all 5,013,773 other acute hospitalizations in the study period. Results: The probability of discharge among hip fracture patients increased by 5.5 percentage points (95% confidence interval (CI)=5.3– 5.7) per 10 percentage points increase in hospital discharges of patients with other acute conditions. The increased risk of death that could be attributed to a discharge from organizational causes was estimated to 3.7 percentage points (95% CI=1.4– 6.0). The results remained stable under different time adjustments, follow-up periods, and age cut-offs. Conclusion: This study showed that discharges from organizational causes may increase the risk of death among hip fracture patients.publishedVersio

Breast cancer tumor growth estimated through mammography screening data

Introduction Knowledge of tumor growth is important in the planning and evaluation of screening programs, clinical trials, and epidemiological studies. Studies of tumor growth rates in humans are usually based on small and selected samples. In the present study based on the Norwegian Breast Cancer Screening Program, tumor growth was estimated from a large population using a new estimating procedure/model. Methods A likelihood-based estimating procedure was used, where both tumor growth and the screen test sensitivity were modeled as continuously increasing functions of tumor size. The method was applied to cancer incidence and tumor measurement data from 395,188 women aged 50 to 69 years. Results Tumor growth varied considerably between subjects, with 5% of tumors taking less than 1.2 months to grow from 10 mm to 20 mm in diameter, and another 5% taking more than 6.3 years. The mean time a tumor needed to grow from 10 mm to 20 mm in diameter was estimated as 1.7 years, increasing with age. The screen test sensitivity was estimated to increase sharply with tumor size, rising from 26% at 5 mm to 91% at 10 mm. Compared with previously used Markov models for tumor progression, the applied model gave considerably higher model fit (85% increased predictive power) and provided estimates directly linked to tumor size. Conclusion Screening data with tumor measurements can provide population-based estimates of tumor growth and screen test sensitivity directly linked to tumor size. There is a large variation in breast cancer tumor growth, with faster growth among younger women

Molecular subtypes, histopathological grade and survival in a historic cohort of breast cancer patients

Molecular subtyping of breast cancer may provide additional prognostic information regarding patient outcome. However, its clinical significance remains to be established. In this study, the main aims were to discover whether reclassification of breast cancer into molecular subtypes provides more precise information regarding outcome compared to conventional histopathological grading and to study breast cancer-specific survival in the different molecular subtypes. Cases of breast cancer occurring in a cohort of women born between 1886 and 1928 with long-term follow-up were included in the study. Tissue microarrays were constructed from archival formalin-fixed, paraffin-embedded tissue from 909 cases. Using immunohistochemistry and in situ hybridisation as surrogates for gene expression analyses, all cases were reclassified into the following molecular subtypes: Luminal A; Luminal B (HER2−); Luminal B (HER2+); HER2 subtype; Basal phenotype; and five negative phenotype. Kaplan–Meier survival curves and Cox proportional hazards models were used in the analyses. During the first 5 years after diagnosis, there were significant differences in prognosis according to molecular subtypes with the best survival for the Luminal A subtype and the worst for HER2 and five negative phenotype. In this historic cohort of women with breast cancer, differences in breast cancer-specific survival according to subtype occur almost exclusively amongst the histopathological grade 2 tumours. From 5 years after time of diagnosis until the end of follow-up, there appears to be no difference in survival according to molecular subtype or histopathological grade.publishedVersio

Disparities in breast cancer mortality trends between 30 European countries: retrospective trend analysis of WHO mortality database

Objective To examine changes in temporal trends in breast cancer mortality in women living in 30 European countries