Invasive lobular (ILC) versus invasive ductal (IDC) breast cancer (BC): Clinical-pathologic features and clinical outcomes in monoinstitutional series

Background: ILC is less common than IDC and is usually diagnosed at a later stage Purpose:The aim of our study was to investigate different clinico-biological behavior associated to ILC compared to IDC and to evaluate implications on survival outcomes Methods: We analyzed data from 3749 consecutive cases of IBC treated from 1995 to 2008 and classified as ILC, IDC and mixed/other. Relationships with clinical-pathological variables and the impact of ILC/IDC types on Event Free Survival (EFS), Overall Survival (OS) and Post-Progression Survival (PPS) were analyzed. Results: We have identified 445 ILC BC (12%), 3021 IDC (80.5%), 149 mixed (3.9%) and 134 other histotypes (3.6%). Median age was 61 (25-97) years. ILC presented a significantly (p3 ILC pts, in whom a trend of worse prognosis (55.6 vs 60.2%) was observed. Conclusions: ILC pts did not show in our series a better outcome than IDC pts, despite a quite favorable biological pattern

Association of Ideal Cardiovascular Health With Vascular Brain Injury and Incident Dementia

BACKGROUND AND PURPOSE: The American Heart Association (AHA) developed the Ideal-Cardiovascular Health (CVH) index as a simple tool to promote cardiovascular health, yet its association with brain atrophy and dementia remains unexamined. METHODS: Our aim was to investigate the prospective association of Ideal-CVH with vascular brain injury, including the 10-year risks of incident stroke and dementia, as well as cognitive decline and brain atrophy on magnetic resonance imaging, measured over approximately 7 years. We studied 2,750 stroke- and dementia-free Framingham Heart Study Offspring Cohort participants (mean age 62±9 years; 45% men). Ideal-CVH was quantified on a 7-point scale with 1 point awarded for each of the following; non-smoking status, ideal body mass index, regular physical activity, healthy diet, as well as optimum blood pressure, cholesterol, and fasting blood glucose. Both recent (baseline) and remote (6.9 years earlier) Ideal-CVH scores were examined. RESULTS: Recent Ideal-CVH was associated with stroke (Hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.67-0.95), vascular dementia (HR, 0.49; 95% CI, 0.30-0.81), frontal brain atrophy (p=.003), and cognitive decline on tasks measuring visual memory and reasoning (p < .05). In addition to predicting stroke, vascular dementia, whole brain atrophy, and cognitive decline, remote Ideal-CVH was associated with the incidence of all-cause dementia (HR, 0.80; 95% CI, 0.67-0.97) and Alzheimer's disease (HR, 0.79; 95% CI, 0.64-0.98). CONCLUSIONS: Adherence to the AHA's Ideal-CVH factors and behaviours, particularly in midlife, may protect against cerebrovascular disease and dementia

Genomewide Association Studies of Stroke

Background The genes underlying the risk of stroke in the general population remain undetermined. Methods We carried out an analysis of genomewide association data generated from four large cohorts composing the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, including 19,602 white persons (mean [+/- SD] age, 63 +/- 8 years) in whom 1544 incident strokes (1164 ischemic strokes) developed over an average follow-up of 11 years. We tested the markers most strongly associated with stroke in a replication cohort of 2430 black persons with 215 incident strokes (191 ischemic strokes), another cohort of 574 black persons with 85 incident strokes (68 ischemic strokes), and 652 Dutch persons with ischemic stroke and 3613 unaffected persons. Results Two intergenic single-nucleotide polymorphisms on chromosome 12p13 and within 11 kb of the gene NINJ2 were associated with stroke (P<5x10(-8)). NINJ2 encodes an adhesion molecule expressed in glia and shows increased expression after nerve injury. Direct genotyping showed that rs12425791 was associated with an increased risk of total (i.e., all types) and ischemic stroke, with hazard ratios of 1.30 (95% confidence interval [CI], 1.19 to 1.42) and 1.33 (95% CI, 1.21 to 1.47), respectively, yielding population attributable risks of 11% and 12% in the discovery cohorts. Corresponding hazard ratios were 1.35 (95% CI, 1.01 to 1.79; P = 0.04) and 1.42 (95% CI, 1.06 to 1.91; P = 0.02) in the large cohort of black persons and 1.17 (95% CI, 1.01 to 1.37; P = 0.03) and 1.19 (95% CI, 1.01 to 1.41; P = 0.04) in the Dutch sample; the results of an underpowered analysis of the smaller black cohort were nonsignificant. Conclusions A genetic locus on chromosome 12p13 is associated with an increased risk of stroke

Genome-wide association studies of cerebral white matter lesion burden

Objective: White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified. Methods: We performed a meta-analysis of genome-wide association studies (GWASs) for WMH burden in 9,361 stroke-free individuals of European descent from 7 community-based cohorts. Significant findings were tested for replication in 3,024 individuals from 2 additional cohorts. Results: We identified 6 novel risk-associated single nucleotide polymorphisms (SNPs) in 1 locus on chromosome 17q25 encompassing 6 known genes including WBP2, TRIM65, TRIM47, MRPL38, FBF1, and ACOX1. The most significant association was for rs3744028 (pdiscovery= 4.0 × 10-9; preplication= 1.3 × 10-7; pcombined= 4.0 × 10-15). Other SNPs