The 70-Gene Prognostic Signature for Korean Breast Cancer Patients

Purpose: A 70-gene prognostic signature has prognostic value in patients with node-negative breast cancer in Europe. This diagnostic test known as “MammaPrint TM (70-gene prognostic signature)” was recently validated and implementation was feasible. Therefore, we assessed the 70-gene prognostic signature in Korean patients with breast cancer. We compared the risk predicted by the 70-gene prognostic signature with commonly used clinicopathological guidelines among Korean patients with breast cancer. We also analyzed the 70-gene prognostic signature and clinicopathological feature of the patients in comparison with a previous validation study. Methods: Forty-eight eligible patients with breast cancer (clinical T1-2N0M0) were selected from four hospitals in Korea. Fresh tumor samples were analyzed with a customized microarray for the 70-gene prognostic signature. Concordance between the risk predicted by the 70-gene prognosti

An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation

BACKGROUND PREDICT is a breast cancer prognostic and treatment benefit model implemented online. The overall fit of the model has been good in multiple independent case series, but PREDICT has been shown to underestimate breast cancer specific mortality in women diagnosed under the age of 40. Another limitation is the use of discrete categories for tumour size and node status resulting in 'step' changes in risk estimates on moving between categories. We have refitted the PREDICT prognostic model using the original cohort of cases from East Anglia with updated survival time in order to take into account age at diagnosis and to smooth out the survival function for tumour size and node status. METHODS Multivariable Cox regression models were used to fit separate models for ER negative and ER positive disease. Continuous variables were fitted using fractional polynomials and a smoothed baseline hazard was obtained by regressing the baseline cumulative hazard for each patients against time using fractional polynomials. The fit of the prognostic models were then tested in three independent data sets that had also been used to validate the original version of PREDICT. RESULTS In the model fitting data, after adjusting for other prognostic variables, there is an increase in risk of breast cancer specific mortality in younger and older patients with ER positive disease, with a substantial increase in risk for women diagnosed before the age of 35. In ER negative disease the risk increases slightly with age. The association between breast cancer specific mortality and both tumour size and number of positive nodes was non-linear with a more marked increase in risk with increasing size and increasing number of nodes in ER positive disease. The overall calibration and discrimination of the new version of PREDICT (v2) was good and comparable to that of the previous version in both model development and validation data sets. However, the calibration of v2 improved over v1 in patients diagnosed under the age of 40. CONCLUSIONS The PREDICT v2 is an improved prognostication and treatment benefit model compared with v1. The online version should continue to aid clinical decision making in women with early breast cancer

Trends in incidence, mortality and survival in women with breast cancer from 1985 to 2012 in Granada, Spain: a population-based study

The incidence of breast cancer has increased since the 1970s. Despite favorable trends in prognosis, the role of changes in clinical practice and the introduction of screening remain controversial. We examined breast cancer trends to shed light on their determinants Overall, age-adjusted (European Standard Population) incidence rates increased from 48.0 cases × 100,000 women in 1985–1989 to 83.4 in 2008–2012, with an annual percentage change (APC) of 2.5% (95%CI, 2.1–2.9) for 1985–2012. The greatest increase was in women younger than 40 years (APC 3.5, 95%CI, 2.4–4.8). For 2000–2012 the incidence trend increased only for stage I tumors (APC 3.8, 95%CI, 1.9–5.8). Overall age-adjusted breast cancer mortality decreased (APC − 1, 95%CI, − 1.4 – − 0.5), as did mortality in the 50–69 year age group (APC − 1.3, 95%CI, − 2.2 – − 0.4). Age-standardized net survival increased from 67.5% at 5 years in 1985–1989 to 83.7% in 2010–2012. All age groups younger than 70 years showed a similar evolution. Five-year net survival rates were 96.6% for patients with tumors diagnosed in stage I, 88.2% for stage II, 62.5% for stage III and 23.3% for stage IV. Breast cancer incidence is increasing – a reflection of the evolution of risk factors and increasing diagnostic pressure. After screening was introduced, the incidence of stage I tumors increased, with no decrease in the incidence of more advanced stages. Reductions were seen for overall mortality and mortality in the 50–69 year age group, but no changes were found after screening implementation. Survival trends have evolved favorably except for the 70–84 year age group and for metastatic tumors.This study was supported by a grant from the Acción Estratégica en Salud plan for the High Resolution Project on Prognosis and Care of Cancer Patients (No. AC14/00036) awarded by the Spanish Ministry of Economy and Competitiveness and co-funded by the European Regional Development Fund (ERDF)

Polarity in ZnO nanowires: A critical issue for piezotronic and piezoelectric devices

The polar and piezoelectric nature of the wurtzite structure of ZnO nanowires with a high aspect ratio at nanoscale dimensions is of high interest for piezotronic and piezoelectric devices, but a number of issues related to polarity are still open and deserve a particular attention. In this context, chemical bath deposition offers a unique opportunity to select the O- or Zn-polarity of the resultant nanowires and is further compatible with the fabrication processes of flexible devices. The control and use of the polarity in ZnO nanowires grown by chemical bath deposition opens a new way to greatly enhance the performance of the related piezotronic and piezoelectric devices. However, polarity as an additional tunable parameter should be considered with care because it has a strong influence on many processes and properties. The present review is intended to report the most important consequences related to the polarity in ZnO nanowires for piezotronic and piezoelectric devices. After introducing the basic principles involving crystal polarity in ZnO, a special emphasis is placed on the effects of polarity on the nucleation and growth mechanisms of ZnO nanowires using chemical bath deposition, defect incorporation and doping, electrical contacts and device properties

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases

Validity of the online PREDICT tool in older patients with breast cancer: a population-based study

BACKGROUND: Predicting breast cancer outcome in older patients is challenging, as it has been shown that the available tools are not accurate in older patients. The PREDICT tool may serve as an alternative tool, as it was developed in a cohort that included almost 1800 women aged 65 years or over. The aim of this study was to assess the validity of the online PREDICT tool in a population-based cohort of unselected older patients with breast cancer. METHODS: Patients were included from the population-based FOCUS-cohort. Observed 5- and 10-year overall survival were estimated using the Kaplan–Meier method, and compared with predicted outcomes. Calibration was tested by composing calibration plots and Poisson Regression. Discriminatory accuracy was assessed by composing receiver-operator-curves and corresponding c-indices. RESULTS: In all 2012 included patients, observed and predicted overall survival differed by 1.7%, 95% confidence interval (CI)=−0.3–3.7, for 5-year overall survival, and 4.5%, 95% CI=2.3–6.6, for 10-year overall survival. Poisson regression showed that 5-year overall survival did not significantly differ from the ideal line (standardised mortality ratio (SMR)=1.07, 95% CI=0.98–1.16, P=0.133), but 10-year overall survival was significantly different from the perfect calibration (SMR=1.12, 95% CI=1.05–1.20, P=0.0004). The c-index for 5-year overall survival was 0.73, 95% CI=0.70–0.75, and 0.74, 95% CI=0.72–0.76, for 10-year overall survival. CONCLUSIONS: PREDICT can accurately predict 5-year overall survival in older patients with breast cancer. Ten-year predicted overall survival was, however, slightly overestimated