Association between Ancestry-Specific 6q25 Variants and Breast Cancer Subtypes in Peruvian Women

Background: Breast cancer incidence in the United States is lower in Hispanic/Latina (H/L) compared with African American/ Black or Non-Hispanic White women. An Indigenous American breast cancer-protective germline variant (rs140068132) has been reported near the estrogen receptor 1 gene. This study tests the association of rs140068132 and other polymorphisms in the 6q25 region with subtype-specific breast cancer risk in H/Ls of high Indigenous American ancestry. Methods: Genotypes were obtained for 5,094 Peruvian women with (1,755) and without (3,337) breast cancer. Associations between genotype and overall and subtype-specific risk for the protective variant were tested using logistic regression models and conditional analyses, including other risk-associated polymorphisms in the region. Results: We replicated the reported association between rs140068132 and breast cancer risk overall [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.47-0.59], as well as the lower odds of developing hormone receptor negative (HR-) versus HR+ disease (OR, 0.77; 95% CI, 0.61-0.97). Models, including HER2, showed further heterogeneity with reduced odds for HR+HER2+ (OR, 0.68; 95% CI, 0.51-0.92), HR-HER2+ (OR, 0.63; 95% CI, 0.44-0.90) and HR-HER2- (OR, 0.77; 95% CI, 0.56-1.05) compared with HR+HER2-. Inclusion of other risk-associated variants did not change these observations. Conclusions: The rs140068132 polymorphism is associated with decreased risk of breast cancer in Peruvians and is more protective against HR- and HER2+ diseases independently of other breast cancer-associated variants in the 6q25 region. Impact: These results could inform functional analyses to understand the mechanism by which rs140068132-G reduces risk of breast cancer development in a subtype-specific manner. They also illustrate the importance of including diverse individuals in genetic studies.National Institutes of HealthRevisión por pare

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Potential Distribution and Identification of Critical Areas for the Preservation and Recovery of Three Species of <i>Cinchona</i> L. (Rubiaceae) in Northeastern Peru

The genus Cinchona L. has important medicinal, cultural, and economic value and is the emblematic tree of Peru. The genus is mainly found in the cloud forests of the Andes. However, the expansion of agriculture and livestock farming in the department of Amazonas is degrading these ecosystems and has reduced the size of the genus’s populations. In this work, we model the potential distribution under current conditions of three Cinchona species (C. capuli L. Anderson, C. macrocalyx Pav. Ex DC., and C. pubescens Vahl.) to identify areas with a high likelihood of species presence and their key conservation and reforestation zones. We fitted a maximum entropy (MaxEnt) model using nineteen bioclimatic variables, three topographic variables, nine edaphic variables, and solar radiation. Under current conditions, the potential distribution of C. capuli covers 17.22% (7243.98 km2); C. macrocalyx, 29.11% (12,238.91 km2); and C. pubescens, 22.94% (9647.63 km2) of the study area, which was mostly located in central and southern Amazonas. Only 24.29% (25.51% of C. capuli, 21.02% of C. macrocalyx, and 26.35% of C. pubescens) of the potential distributions are within protected areas, while 10,987.22 km2 of the surface area of the department of Amazonas is degraded, of which 29.80% covers the area of probable occurrence of C. capuli, 38.72% of C. macrocalyx, and 34.82% of C. pubescens. Consequently, it is necessary to promote additional conservation strategies for Cinchona, including the establishment of new protected areas and the recovery of degraded habitats, in order to protect this species

Long-Term Outcomes of an International Cooperative Study of Intraoperative Radiotherapy Upfront Boost With Low Energy X-Rays in Breast Cancer.

The purpose of this study was to assess the effectivity of upfront kilovoltage intraoperative radiotherapy (IORT) as a boost in high-risk early-stage breast cancer patients from an international pooled cohort. Patients from four centers in three different countries were retrospectively screened. Those with a minimum 1-year follow-up were included. Cumulative local (LR), regional (RR), and distant metastasis rates (DM) were analyzed. Additionally, the estimated overall survival (OS) was assessed. The Cox regression analysis was performed to identify failure predicting factors. A total of 653 patients from centers in Peru, Spain, and Germany were included. The median follow-up was 55 (12-180) months, and age was 58 (27-86) years. Clinical tumor (T) staging was T1 65.85%, T2 30.17%, and T3 3.98%. Positive margins were found in 7.9% and in-situ component in 20.06%. The median IORT dose was 20 (6-20). The median time from IORT to EBRT was 74.5 (13-364) days. An overall 3.4% (n = 22) of patients developed local recurrence at some point during follow-up. The 12-, 60-, and 120-month cumulative LR were 0.3%, 2.3%, and 7.9%, respectively. After multivariate analysis, only age Upfront boost with IORT yields similar local control outcomes to those EBRT-based reports. Results from prospective trials, regarding toxicity, cosmesis, and effectivity are awaited to confirm these findings

Measurements of sulfur dioxide,ozone and ammonia concentrations in Asia,Africa,and South America using passive samplers

Measurements of gaseous SO2,NH3,and O3 using IVL passive sampler technology were obtained during a pilot measurement program initiated as a key component of the newly established WMO/GAW Urban Research Meteorology and Environment (GURME) project. Monthly measurements were obtained at 50 stations in Asia,Africa, South America,and Europe. The median SO2 concentrations vary from a high of 13 ppb at Linan,China,to o0.03 ppb at four stations. At 30 of 50 regional stations,the observed median concentrations are o1 ppb. Median ammonia concentrations range from 20 ppb at Dhangadi,India,to o1 ppb at nine stations. At 27 of regional stations,the ambient ammonia levels exceed 1 ppb. The median ozone concentrations vary from a maximum of 45 ppb at Waliguan Mountain,China,to 8 ppb in Petit Saut,French Guiana. In general,the highest ozone values are found in the mid- latitudes,with the Northern hemisphere mid-latitude values exceeding the Southern hemisphere mid-latitude levels,and the lowest values are typically found in the tropical regions

Lymph node ratio as best prognostic factor in triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy

Although lymph node status (ypN) is one of the most important prognostic factors of survival, the lymph node ratio (LNR) has emerged as an equitable factor. We aimed to compare the prognostic value of both ypN and LNR in patients with residual triple-negative breast cancer (TNBC) after neo-adjuvant chemotherapy (NAC). This was a retrospective cohort study of patients treated in a tertiary care center during the period 2000-2014. We stratified the population based on LNR (≤0.20, 0.20-0.65, and >0.65) and ypN (N1, N2, and N3) status. The overall survival (OS) and progression-free survival (PFS) were estimated with Kaplan-Meier curves and the log-rank + test. We further compared patient mortality and disease recurrence using multivariate Cox regression analysis. We evaluated 169 patients with a median follow-up of 87 months. At 2 years of follow-up, patients with low-risk LNR compared to those with moderate and high risk had a higher PFS (54% vs 31% vs 18%, respectively; P < .001) and OS (74% vs 64% vs 45%, respectively; P < .001). Moreover, ypN1 patients compared to ypN2 and ypN3 showed similar results in PFS (53% vs 35% vs 19%, respectively; P = .001) and OS (73% vs 69% vs 43%, respectively; P < .001). Compared to the low-risk population, patients with moderate (hazard ratio [HR]: 3.50; 95% confidence interval [CI]: 1.41-8.71) and high risk (HR: 6.90; 95% CI: 2.29-20.77) had a worse PFS. Regarding OS, moderate-risk (HR: 2.85; 95% CI: 1.10-7.38) and high-risk patients (HR: 6.48; 95% CI: 2.13-19.76) showed considerably worse outcomes. On the other hand, ypN staging was not associated with PFS or OS in the multivariate analysis. The LNR is a better prognostic factor of survival than ypN. The LNR should be considered in the stratification of risk after NAC in patients with TNBC