Citations

Clinical data captured in electronic medical records accurately identify cases and controls for genome-wide association studies.

OBJECTIVE The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS. RESEARCH DESIGN AND METHODS Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of ∼2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected. RESULTS Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from ∼9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure. CONCLUSIONS Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants.

Declines in heart disease and stroke mortality rates are conventionally attributed to reductions in cigarette smoking, recognition and treatment of hypertension and diabetes, effective medications to improve serum lipid levels and to reduce clot formation, and general lifestyle improvements. Recent evidence implicates these and other cerebrovascular factors in the development of a substantial proportion of dementia cases. Analyses were undertaken to determine whether corresponding declines in age‐specific prevalence and incidence rates for dementia and cognitive impairment have occurred in recent years. Data spanning 1 or 2 decades were examined from community‐based epidemiological studies in Minnesota, Illinois, and Indiana, and from the Health and Retirement Study, which is a national survey. Although some decline was observed in the Minnesota cohort, no statistically significant trends were apparent in the community studies. A significant reduction in cognitive impairment measured by neuropsychological testing was identified in the national survey. Cautious optimism appears justified.

Passive surveillance for disease is a public health approach that relies on documentation available within existing health records for the region or community being studied. Its two primary advantages over active case‐finding are the lower cost of research and the lower burden on the population under study. The effectiveness of passive case‐finding depends on the comprehensiveness of the healthcare coverage in a given community and the adequacy of the available medical records. The Rochester Epidemiology Project has permitted dementia case detection for Olmsted County, Minnesota, using a medical records‐linkage system. These data were compared with case ascertainment using direct assessment of individuals in an epidemiological study of the same community. At the Group Health Research Institute, investigators compared dementia and Alzheimer's disease cases detected using an electronic medical record database search with those identified by a parallel active case‐finding study. In this article, the advantages and disadvantages of passive case‐finding were discussed, and the following conclusion was drawn: the purpose of the study being conducted should determine the case‐finding approach that is to be used.

Abstract Abstract #76 Background: QOL and MH outcomes were integrated into the NSABP B-30 trial as secondary outcomes to the efficacy analyses which are being presented separately. Explicit secondary aims of the NSABP B-30 study were 1) to compare toxicities among the regimens, 2) to compare QOL, and 3) to examine differences in amenorrhea and its relationship to symptoms, QOL, and efficacy. Here we examine the secondary aims of the study as a companion to the efficacy results that are presented separately.
 Materials and Methods: 5351 pts with cT1-3, N0-1, M0 were enrolled from 3/1/99 to 3/31/2004. 2170 were enrolled on the QOL study, and 2449 were enrolled on the MH study and were randomized to one of three treatment groups: Group 1 [doxorubicin (A) 60 mg/m2 and C 600 mg/m2 q 3 weeks (wks) x 4 followed by docetaxel (T) 100 mg/m2 q 3 wks x 4; Group 2 [A 50 mg/m2 and T 75 mg/m2 q 3 wks x 4]; Group 3 [A 50 mg/m2 T 75 mg/m2 and cyclophosphamide (C) 500 mg/m2 q 3 wks x 4]. All patients with ER-positive tumors received hormonal therapy after completing chemotherapy. Preliminary results from Group 1 have been reported previously (Swain, et al. Breast Cancer Res Treat, 2008).
 Results: The protocol specifies that 800 deaths are required for the definitive analysis of treatment, QOL, and MH outcomes, which are expected to occur by fall 2008. For this final report, results from a comparison of the three arms will be analyzed and presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 76.

Abstract Abstract #75 Background: The primary aims of this study were to determine 1) if a concurrent regimen of therapy containing cyclophosphamide compared to a sequential regimen containing cyclophosphamide would prolong disease-free survival (DFS) and overall survival (OS) and 2) if a regimen without cyclophosphamide was at least as efficacious as the two regimens containing cyclophosphamide. The secondary aims were to compare toxicities among the three regimens and to compare differences in amenorrhea in premenopausal women in each arm and its relationship to outcome.
 Materials and Methods: 5351 pts with cT1-3, N0-1, M0 were enrolled from 3/1/99 to 3/31/2004. 1783 pts were randomized to Group 1 [doxorubicin (A) 60 mg/m2 and C 600 mg/m2 q 3 weeks (wks) x 4 followed by docetaxel (T) 100 mg/m2 q 3 wks x 4], 1784 pts to Group 2 [A 50 mg/m2 and T 75 mg/m2 q 3 wks x 4], and 1784 to Group 3 [A 50 mg/m2 T 75 mg/m2 and cyclophosphamide (C) 500 mg/m2 q 3 wks x 4]. All patients with ER-positive tumors received hormonal therapy after completing chemotherapy. The protocol specifies that 800 deaths are required for the definitive analysis. This is expected to occur by Fall 2008.
 Results: Mean time on study is currently 79 months. At entry, 46% of pts were < 49 yrs; 54% were > 50 yrs. 82% were white, 10% black, 4% Hispanic. 66% had 1-3 positive nodes, 26% had 4-9, and 8% had 10+. 75% of pts were ER pos. 49% had lumpectomy, 51% mastectomy, and 24% local/regional radiotherapy. Mean tumor size was 2.5 cm. The presentation will include the first results of DFS, OS, and relevant toxicities from the trial. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 75.

Abstract Abstract #3057 Introduction: Patients (pts) with ER/PR/HER2 negative advanced breast cancer (triple negative, TN, basal-like) have limited treatment options and a poor prognosis. Ixabepilone (ixa), the first in a new class of antineoplastic agents, showed clinical benefit in combination with capecitabine (C) in 2 large clinical trials in metastatic breast cancer (MBC) pts either resistant to (study 046; JCO, 2007) or pretreated with anthracycline (A) and taxanes (T) (study 048). In 048, ixa + C, compared to C alone, demonstrated significant increases in PFS (HR 0.79 [0.69-0.90]) and ORR (43 vs. 29%). A trend towards increased OS was seen in both 048 (HR 0.90 [0.78-1.03]) and 046 (HR 0.90 [0.77-1.05]), which did not reach statistical significance. Here we present a pooled analysis of efficacy endpoints (ORR, PFS and OS) in pts with TN disease from these 2 phase III studies.
 Methods: 1973 pts with MBC previously treated with A and T were randomized in 2 phase III trials (046 and 048) to receive either ixa (40 mg/m2 IV over 3h Q3w) + C (1000 mg/m2 PO BID x14d Q3w) or C alone (1250 mg/m2 PO BID x14d Q3w). Due to the similarity of the study populations, individual pt data from both studies was pooled to better evaluate treatment effect within pre-planned patient subgroups.
 Results: 443 pts had TN disease in the two studies combined. ORR and PFS were superior in pts receiving combination therapy compared to those on C alone with a trend towards improved survival that did not reach statistical significance.
 
 Conclusions: Ixa + C is the first combination to show statistically significant PFS benefit in pts with advanced TN breast cancer from a pooled analysis of 2 phase III trials. Clinical benefit was consistently seen pts with TN disease in the individual studies as well. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3057.

Purpose Hand-foot syndrome (HFS) is a dose-limiting toxicity of capecitabine for which no effective preventative treatment has been definitively demonstrated. This trial was conducted on the basis of preliminary data that a urea/lactic acid–based topical keratolytic agent (ULABTKA) may prevent HFS. Patients and Methods A randomized, double-blind phase III trial evaluated 137 patients receiving their first ever cycle of capecitabine at a dose of either 2,000 or 2,500 mg/m2 per day for 14 days. Patients were randomly assigned to a ULABTKA versus a placebo cream, which was applied to the hands and feet twice per day for 21 days after the start of capecitabine. Patients completed an HFS diary (HFSD) daily. HFS toxicity grade (Common Terminology Criteria for Adverse Events [CTCAE] v3.0) was also collected at baseline and at the end of each cycle. The primary end point was the incidence of moderate/severe HFS symptoms in the first treatment cycle, based on the patient-reported HFSD. Results The percentage of patients with moderate/severe HFS symptoms was not different between groups, being 13.6% in the ULABTKA arm and 10.2% in the placebo arm (P = .768 by Fisher's exact test). The odds ratio was 1.37 (95% CI, 0.37 to 5.76). Cycle 1 CTCAE skin toxicity was higher in the ULABTKA arm but not significantly so (33% v 27%; P = .82). No significant differences were observed in other toxicities between groups. Conclusion These data do not support the efficacy of a ULABTKA cream for preventing HFS symptoms in patients receiving capecitabine.