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

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

Intermittent mild negative pressure applied to the lower limb in patients with spinal cord injury and chronic lower limb ulcers: a crossover pilot study

Study design Randomized, assessor-blinded crossover pilot study. Objectives To explore the use of an intermittent negative pressure (INP) device for home use in addition to standard wound care (SWC) for patients with spinal cord injury (SCI) and chronic leg and foot ulcers before conducting a superiority trial. Setting Patient homes and outpatient clinic. Methods A 16-week crossover trial on 9 SCI patients (median age: 57 years, interquartile range [IQR] 52–66), with leg ulcers for 52 of weeks (IQR: 12–82) duration. At baseline, patients were allocated to treatment with INP + SWC or SWC alone. After 8 weeks, the ulcers were evaluated. To assess protocol adherence, the patients were then crossed over to the other group and were evaluated again after another 8 weeks. Lower limb INP treatment consisted of an airtight pressure chamber connected to an INP generator (alternating 10 s −40mmHg/7 s atmospheric pressure) used 2 h/day at home. Ulcer healing was assessed using a photographic wound assessment tool (PWAT) and by measuring changes in wound surface area (WSA). Results Seven of nine recruited patients adhered to a median of 90% (IQR: 80–96) of the prescribed 8-week INP-protocol, and completed the study without side effects. PWAT improvement was observed in 4/4 patients for INP + SWC vs. 2/5 patients for SWC alone (P = 0.13). WSA improved in 3/4 patients allocated to INP + SWC vs. 3/5 patients in SWC alone (P = 0.72). Conclusions INP can be used as a home-based treatment for patients with SCI, and its efficacy should be tested in an adequately sized, preferably multicenter randomized trial.måsjekke

Empirical evaluation of prediction intervals for cancer incidence

BACKGROUND: Prediction intervals can be calculated for predicting cancer incidence on the basis of a statistical model. These intervals include the uncertainty of the parameter estimates and variations in future rates but do not include the uncertainty of assumptions, such as continuation of current trends. In this study we evaluated whether prediction intervals are useful in practice. METHODS: Rates for the period 1993–97 were predicted from cancer incidence rates in the five Nordic countries for the period 1958–87. In a Poisson regression model, 95% prediction intervals were constructed for 200 combinations of 20 cancer types for males and females in the five countries. The coverage level was calculated as the proportion of the prediction intervals that covered the observed number of cases in 1993–97. RESULTS: Overall, 52% (104/200) of the prediction intervals covered the observed numbers. When the prediction intervals were divided into quartiles according to the number of cases in the last observed period, the coverage level was inversely proportional to the frequency (84%, 52%, 46% and 26%). The coverage level varied widely among the five countries, but the difference declined after adjustment for the number of cases in each country. CONCLUSION: The coverage level of prediction intervals strongly depended on the number of cases on which the predictions were based. As the sample size increased, uncertainty about the adequacy of the model dominated, and the coverage level fell far below 95%. Prediction intervals for cancer incidence must therefore be interpreted with caution

CD74-downregulation of placental macrophage-trophoblastic interactions in preeclampsia

Rationale: MWe hypothesized that Cluster of differentiation 74 (CD74) downregulation on placental macrophages, leading to altered macrophage-trophoblast interaction, is involved in preeclampsia. Objective: Preeclamptic pregnancies feature hypertension, proteinuria and placental anomalies. Feto-placental macrophages regulate villous trophoblast differentiation during placental development. Disturbance of this well-balanced regulation can lead to pathological pregnancies. Methods and Results: We performed whole genome expression analysis of placental tissue. CD74 was one of the most downregulated genes in placentas from preeclamptic women. By RT-PCR, we confirmed this finding in early onset (<34 gestational week, n=26) and late onset (≥34 gestational week, n=24) samples from preeclamptic women, compared to healthy pregnant controls (n=28). CD74 protein levels were analyzed by Western blot and flow cytometry. We identified placental macrophages to express CD74 by immunofluorescence, flow cytometry and RT-PCR. CD74-positive macrophages were significantly reduced in preeclamptic placentas compared to controls. CD74-silenced macrophages showed that the adhesion molecules ALCAM, ICAM4, and Syndecan-2, as well as macrophage adhesion to trophoblasts were diminished. Naïve and activated macrophages lacking CD74 showed a shift towards a pro-inflammatory signature with an increased secretion of TNF , CCL5, and MCP-1, when co-cultured with trophoblasts compared to control macrophages. Trophoblasts stimulated by these factors express more CYP2J2, sFlt1, TNF and IL-8. CD74-knockout mice showed disturbed placental morphology, reduced junctional zone, smaller placentas and impaired spiral artery remodeling with fetal growth restriction. Conclusions: CD74 downregulation in placental macrophages is present in preeclampsia. CD74 downregulation leads to altered macrophage activation towards a pro-inflammatory signature and a disturbed crosstalk with trophoblasts