Association Between Daily Timing of Everolimus and Survival in High-Risk HR+/HER2- Early Breast Cancer: A Sub-Analysis of the UCBG-UNIRAD Trial.

In the UNIRAD phase III trial, evening intake of tamoxifen was previously associated with improved disease-free survival (DFS), while no timing effect was observed for aromatase inhibitors. This sub-study evaluated whether the timing of everolimus intake affects DFS in patients receiving adjuvant endocrine therapy (ET). A total of 1278 patients with high-risk HR+/HER2- early breast cancer were randomized to receive adjuvant ET with either placebo or everolimus.

Hidden costs and unmet supportive care needs among individuals with experience of breast cancer and their carers in the United Kingdom.

Background: The impact of cancer transcends physical health, affecting mental wellbeing, financial stability, and ability to perform daily tasks, influencing not only patients but also the broader community.

Methods: Online anonymous surveys (24/01/2023-03/03/2023) were disseminated via charities to individuals treated for breast cancer in the UK and their carers. Multivariable ordered logistic regression models were used to investigate demographic, cancer-related and employment factors associated with physical, wellbeing and financial Quality-of-Life (QoL).

Predicting ovarian function loss after chemotherapy and anti-HER2 therapy in young breast cancer patients.

Background: The ability to predict ovarian function loss after anticancer treatment is important for appropriate oncofertility counselling and to aid in therapy decision-making for young women with early breast cancer (eBC).

Methods: This biomarker analysis of the BETH (NCT00625898) and KAITLIN (NCT01966471) randomized trials investigated anti-Müllerian hormone (AMH) use, alone and combined with follicle stimulating hormone (FSH) and estradiol (E2), for predicting ovarian function loss following currently adopted chemotherapy and anti-HER2 therapy in premenopausal women with HER2-positive eBC.Serum samples were centrally tested measuring AMH, FSH and E2 using Roche Elecsys assays.

Advancing equitable access to innovation in breast cancer.

This manuscript critically examines the challenges associated with the design and conduct of academic global breast cancer trials outside the influence of pharmaceutical companies, leveraging insights from the Breast International Group (BIG). In the past 4 decades significant declines in breast cancer mortality have occurred, partly related to industry-academic clinical and translational partnerships with long term study follow up. However, in the past decade these partnerships have largely uncoupled.

Reduced duration adjuvant trastuzumab in the treatment of patients with HER2-positive breast cancer: a meta-analysis of randomised controlled non-inferiority trials including IPD data.

Objectives: Adjuvant trastuzumab in combination with chemotherapy has significantly improved survival in patients with HER2-positive early breast cancer but, since introduction in 2005, the 12 months duration has been questioned and trials have tested shorter durations.

Methods And Analysis: A systematic review and meta-analysis using individual patient data (IPD) (when available) from non-inferiority trials of reduced duration trastuzumab was carried out according to PRISMA-IPD guidelines. Primary outcome was invasive disease-free survival (IDFS); secondary outcomes were distant relapse-free survival (DRFS) and overall survival (OS).

Patient-reported outcomes from DESTINY-Breast04: trastuzumab deruxtecan versus physician's choice of chemotherapy in patients with HER2-low mBC.

Background: The phase 3 DESTINY-Breast04 trial demonstrated superior efficacy and acceptable safety with trastuzumab deruxtecan (T-DXd) vs physician's choice of chemotherapy in previously treated patients with human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer (mBC). We report the patient-reported outcomes (PROs), focusing on the hormone receptor-positive cohort.

Patients And Methods: Patients were randomized 2:1 to T-DXd (5.

Morphology of the Upper Post Canine Complex of Pleistocene Ponginae From Vietnam-Anatomical Variability and Systematics.

Objectives: To examine the morphological variability of the isolated upper post-canine teeth currently allocated to Pongo and Langsonia from northern Vietnam. To revise the taxonomy and assess the systematics of the Middle and Late Pleistocene Ponginae based on the morphological and metric variation and the identification of derived features within samples.

Materials And Methods: A series of correspondent analyses were generated against a large database of morphological (phenetic) characters scored for each tooth.

Climate change impacts and sustainability integration among breast international group members.

Background: Integration of sustainability measures into clinical research would translate into less healthcare related climate impacts.

Methods: We assessed climate change impacts, existing sustainability engagement, and challenges and facilitators to climate change mitigation strategies among Breast International Group (BIG) members. A 30 item web based survey assessing climate impacts, sustainability engagement, challenges to and facilitators of engagement, and sustainability integration in funding applications was developed, and circulated electronically between November 2023 and March 2024.

Targeting Chronic Biofilm Infections With Patient-derived Phages: An In Vitro and Ex Vivo Proof-of-concept Study in Patients With Left Ventricular Assist Devices.

Background: Phage therapy is being reconsidered as a valuable approach to combat antimicrobial resistance. We recently established a personalized phage therapy pipeline in healthy volunteers, where therapeutic phages were isolated from individuals' skin microbiota. In this study, we aim to validate this pipeline in end-stage heart failure patients supported by left ventricular assist devices (LVADs), focusing on phages targeting , a common pathogen responsible for LVAD infections.

A New Look at an Old Face: The Hoà Binh Late Pleistocene Pongo Skull and Other Faciodental Fragments From Breccia Caves in Vietnam-A Morphometric Assessment With Taxonomic Implications.

Objectives: The taxonomic status of the Middle and Late Pleistocene pongines from northern Vietnam remains obscure. Two current schemes dominate. The first has multiple species of Pongo and Langsonia occupying the region during the late Middle and Late Pleistocene.

Machine learning-based spatial characterization of tumor-immune microenvironment in the EORTC 10994/BIG 1-00 early breast cancer trial.

Breast cancer (BC) represents a heterogeneous ecosystem and elucidation of tumor microenvironment components remains essential. Our study aimed to depict the composition and prognostic correlates of immune infiltrate in early BC, at a multiplex and spatial resolution. Pretreatment tumor biopsies from patients enrolled in the EORTC 10994/BIG 1-00 randomized phase III neoadjuvant trial (NCT00017095) were used; the CNN11 classifier for H&E-based digital TILs (dTILs) quantification and multiplex immunofluorescence were applied, coupled with machine learning (ML)-based spatial features.

Long-Term Engraftment of Cryopreserved Human Neurons for In Vivo Disease Modeling in Neurodegenerative Disease.

The transplantation of human neurons into the central nervous system (CNS) offers transformative opportunities for modeling neurodegenerative diseases in vivo. This study evaluated the survival, integration, and functional properties of cryopreserved forebrain GABAergic neurons (iGABAs) derived from human induced pluripotent stem cells (iPSCs) across three species used in translational research. iGABAs were stereotactically injected into the striatum of Sprague-Dawley rats, immunodeficient RNU rats, R6/2 Huntington's disease (HD) mice, wild-type controls, and Cynomolgus monkeys.

A pooled analysis evaluating prognostic significance of Residual Cancer Burden in invasive lobular breast cancer.

Residual Cancer Burden (RCB) after neoadjuvant chemotherapy (NAC) is validated to predict event-free survival (EFS) in breast cancer but has not been studied for invasive lobular carcinoma (ILC). We studied patient-level data from a pooled cohort across 12 institutions. Associations between RCB index, class, and EFS were assessed in ILC and non-ILC with mixed effect Cox models and multivariable analyses.

An international Phase IV field study - psychometric properties of the updated module on assessing quality of life of patients with breast cancer EORTC QLQ-BR42.

Background: The EORTC QLQ-BR23, published in 1996, was one of the first disease-specific questionnaires to assess health-related quality of life (HRQoL) in patients with breast cancer (BC). In the last decades, major changes in BC treatment have occurred, requiring an update of this module. The results of the Phase 1-3 of the study were published in 2019.

Annual versus less frequent mammographic surveillance in people with breast cancer aged 50 years and older in the UK (Mammo-50): a multicentre, randomised, phase 3, non-inferiority trial.

Background: The frequency of mammographic surveillance for women after diagnosis of breast cancer varies globally. The aim of this study was to evaluate whether less than annual mammography was non-inferior in terms of breast cancer-specific survival in women aged 50 years or older.

Methods: Mammo-50 was a multicentre, randomised, phase 3 trial of annual versus less frequent mammography (2-yearly after conservation surgery; 3-yearly after a mastectomy) for women aged 50 years or older at initial diagnosis of invasive or non-invasive breast cancer and who were recurrence free 3 years post curative surgery.

Adjuvant Atezolizumab for Early Triple-Negative Breast Cancer: The ALEXANDRA/IMpassion030 Randomized Clinical Trial.

Importance: Triple-negative breast cancer is an aggressive subtype with a high incidence in young patients, a high incidence in non-Hispanic Black women, and a high risk of progression to metastatic cancer, a devastating sequela with a 12- to 18-month life expectancy. Until recently, one strategy for treating early-stage triple-negative breast cancer was chemotherapy after surgery. However, it was not known whether the addition of immune therapy to postsurgery chemotherapy would be beneficial.

Effectiveness of Digital Mental Health Interventions in the Workplace: Umbrella Review of Systematic Reviews.

Background: There is potential for digital mental health interventions to provide affordable, efficient, and scalable support to individuals. Digital interventions, including cognitive behavioral therapy, stress management, and mindfulness programs, have shown promise when applied in workplace settings.

Objective: The aim of this study is to conduct an umbrella review of systematic reviews in order to critically evaluate, synthesize, and summarize evidence of various digital mental health interventions available within a workplace setting.

Profile analysis in listeners with normal and elevated audiometric thresholds: Behavioral and modeling results.

Profile-analysis experiments measure the ability to discriminate complex sounds based on patterns, or profiles, in their amplitude spectra. Studies of profile analysis have focused on normal-hearing listeners and target frequencies near 1 kHz. To provide more insight into underlying mechanisms, we studied profile analysis over a large target frequency range (0.

An international Delphi consensus on patient preparation for metabolic and bariatric surgery.

Global obesity rates have risen dramatically, now exceeding deaths from starvation. Metabolic and bariatric surgery (MBS), initially for severe obesity (BMI ≥35 kg/m), is performed globally over 500 000 times annually, offering significant metabolic benefits beyond weight loss. However, varying eligibility criteria globally impact patient care and healthcare resources.

Expert recommendations on treatment sequencing and challenging clinical scenarios in human epidermal growth factor receptor 2-positive (HER2-positive) metastatic breast cancer.

Human epidermal growth factor receptor 2 (HER2) overexpression and/or ERBB2 gene amplification occurs in approximately 15-20% of breast cancers and is associated with poor prognosis. While the introduction of HER2-targeted therapies has significantly improved survival in patients with HER2-positive metastatic breast cancer, the incidence of brain metastases has increased due to patients living longer. Current recommendations sequence treatments by line of therapy, as well as by the status of brain metastases in patients with HER2-positive breast cancer.

Improving the sustainability and quality of kidney health care through life cycle assessments, quality improvement, education and technical innovations: the KitNewCare approach.

The European Union (EU)-funded KitNewCare consortium aims to create and manage a comprehensive EU-wide programme focusing on sustainability in Kidney Care. Around 850 million people have chronic kidney disease (CKD) worldwide and by 2030, 6 million will need kidney replacement therapy, mainly haemodialysis. As the world population gets older, projections for the end of the century worsen.

Validation of a breast cancer assay for radiotherapy omission: an individual participant data meta-analysis.

Background: There are currently no molecular tests to identify individual breast cancers where radiotherapy (RT) offers no benefit. Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) is a 16-gene molecular signature developed to identify low-risk cancers where RT will not further reduce recurrence rates.

Methods: An individual participant data meta-analysis was performed in 623 patients of node-negative estrogen receptor-positive and HER2-negative early breast cancer enrolled in 3 RT randomized trials for whom primary tumor material was available for analysis.

Increased Risk for Clinically Significant Sleep Disturbances in Mild Traumatic Brain Injury: An Approach to Leveraging the Federal Interagency Traumatic Brain Injury Research Database.

Study Objectives: The Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System contains individual-patient-level traumatic brain injury (TBI) data, which when combined, allows for the examination of rates and outcomes for key subpopulations at risk for developing sleep disturbance.

Methods: This proof-of-concept study creates a model system for harmonizing data (i.e.

Model-based translation of results from in vitro to in vivo experiments for afabicin activity against Staphylococcus aureus.

Background: Translation of experimental data on antibiotic activity typically relies on pharmacokinetic/pharmacodynamic (PK/PD) indices. Model-based approaches, considering the full antibiotic killing time course, could be an alternative.

Objectives: To develop a mechanism-based modelling framework to assess the in vitro and in vivo activity of the FabI inhibitor antibiotic afabicin, and explore the ability of a model built on in vitro data to predict in vivo outcome.