Evaluating different breast tumor progression models using screening data.

BACKGROUND: Mammography screening is used to detect breast cancer at an early treatable stage, reducing breast cancer mortality. Traditionally, breast cancer has been seen as a disease with only progressive lesions, and here we examine the validity of this assumption by testing if incidence levels after introducing mammography screening can be reproduced assuming only progressive tumors. METHODS: Breast cancer incidence data 1990-2009 obtained from the initially screened Norwegian counties (Akershus, Oslo, Rogaland and Hordaland) was included, covering the time-period before, during and after the introduction of mammography screening. From 1996 women aged 50-69 were invited for biennial public screening. Using estimates of tumor growth and screening sensitivity based on pre-screening and prevalence screening data (1990-1998), we simulated incidence levels during the following period (1999-2009). RESULTS: The simulated incidence levels during the period with repeated screenings were markedly below the observed levels. The results were robust to changes in model parameters. Adjusting for hormone replacement therapy use, we obtained levels closer to the observed levels. However, there was still a marked gap, and only by assuming some tumors that undergo regressive changes or enter a markedly less detectable state, was our model able to reproduce the observed incidence levels. CONCLUSIONS: Models with strictly progressive tumors are only able to partly explain the changes in incidence levels observed after screening introduction in the initially screened Norwegian counties. More complex explanations than a time shift in detection of future clinical cancers seem to be needed to reproduce the incidence trends, questioning the basis for many over-diagnosis calculations. As data are not randomized, similar studies in other populations are wanted to exclude effect of unknown confounders.

Lung function in preterm infants at 3 months corrected age after neonatal LC-PUFA supplementation.

OBJECTIVE: To test the hypothesis that long-chain polyunsaturated fatty acid (LC-PUFA) supplementation improves lung function at 3 months corrected age (CA) compared with standard treatment in very preterm infants. We also aimed to investigate the association between bronchopulmonary dysplasia (BPD), longitudinal growth, and lung function at 3 months CA. METHODS: A secondary analysis from the ImNuT trial, in which 121 infants with gestational age <29 weeks were randomized to a daily supplement with arachidonic acid (ARA) and docosahexaenoic acid (DHA) (ARA:DHA group) or MCT-oil (control group) from birth up to 36 weeks postmenstrual age (PMA). Lung function was assessed at 3 months CA by tidal flow volume loops and the outcomes were the ratio of time to peak tidal expiratory flow to expiratory time (tPTEF /tE ) and tidal volume (VT ) per body weight (mL/kg). RESULTS: Thirty-nine infants in the ARA:DHA group versus 51 in the control group had a successful lung function test. There was no mean difference (MD) in tPTEF /tE ratio (MD: 0.01, 95% confidence interval [CI]: -0.04 to 0.05; p = .77) or VT (MD: 0.09 mL/kg, 95% CI: -0.79 to 0.62; p = .81) between the study groups. The multivariable regression model showed that BPD was associated with tPTEF /tE ratio ≤ 0.25 (p = .03) and that an increase in z score for length after 36 weeks PMA correlated positively with VT (mL/kg) (p = .03). CONCLUSION: Neonatal LC-PUFA supplementation did not improve lung function at 3 months CA in very preterm infants. BPD was independently associated with reduced lung function, while improved linear growth correlated with higher tidal volumes.

Essential Fatty Acid Supplementation and Early Inflammation in Preterm Infants: Secondary Analysis of a Randomized Clinical Trial.

INTRODUCTION: Postnatal inflammation is associated with increased mortality and adverse outcomes in preterm infants. The essential fatty acids arachidonic acid (ARA) and docosahexaenoic acid (DHA) are precursors of lipid mediators with a key role in resolving inflammation. Our aim was to investigate the effect of ARA and DHA supplementation on systemic inflammation in very preterm infants and to identify clinical factors associated with early inflammation. METHODS: Secondary analysis of data from a randomized clinical trial (ImNuT study). Infants with gestational age (GA) less than 29 weeks were randomized to receive a daily enteral supplement with ARA 100 mg/kg and DHA 50 mg/kg (ARA:DHA group) or MCT oil (control group) from the second day of life to 36 weeks postmenstrual age. ARA, DHA, and four proinflammatory cytokines (IL-1ß, IL-6, IL-8, and TNF-α) were analyzed in repeated dried blood samples from birth to day 28 and the area under the curve (AUC) for each variable was calculated. RESULTS: The intention to treat population included 120 infants with mean (SD) GA 26.4 (1.7). The ARA:DHA group had significantly lower IL-6 levels from day 3 to day 28 compared to the control group, mean difference AUC log10 (95% CI): 0.16 (0.03-0.30) pg/mL, p = 0.018. There was no correlation between ARA or DHA blood concentrations and cytokine levels. Having a low gestational age was independently associated with increased levels of all cytokines during the first 4 weeks of life. CONCLUSIONS: Enhanced supplementation with ARA and DHA may modulate inflammation in very preterm infants.