Breast Cancer Susceptibility Gene Sequence Variations and Development of Contralateral Breast Cancer.

Importance: Heterogeneity in development of estrogen receptor (ER)-specific first primary breast cancer exists due to deleterious germline variants in moderate- to high-penetrance breast cancer susceptibility genes, but it is unknown if these associations occur in ER-specific CBC.

Objective: To determine the association of deleterious germline variants in breast cancer susceptibility genes with ER-specific CBC development and whether ER status of the first primary breast cancer modifies these associations.

Design, Setting, And Participants: This case-control study included CBC cases and matched unilateral breast cancer controls from The Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study, a population-based case-control study.

Functional evaluation and clinical classification of BRCA2 variants.

Germline BRCA2 loss-of function variants, which can be identified through clinical genetic testing, predispose to several cancers. However, variants of uncertain significance limit the clinical utility of test results. Thus, there is a need for functional characterization and clinical classification of all BRCA2 variants to facilitate the clinical management of individuals with these variants.

Oral self-management of palbociclib using mobile technology: Findings from a nurse-led randomized controlled trial.

Objective: Test the feasibility and effectiveness of a text message reminder intervention for the self-management of oral anticancer medication in patients with metastatic breast cancer.

Methods: Forty-three females initiating treatment with palbociclib participated in a two-armed prospective randomized clinical trial. Participants were randomized into the control ( = 21) and intervention groups ( = 22) from January 2020 to January 2023.

Correlation Between Disease-Free Survival Endpoints and Overall Survival in Elderly Patients with Early-Stage HER2-Negative Breast Cancer: A SEER-Medicare Analysis.

Introduction: Recent trial-level meta-analyses have established disease-free survival (DFS) as a valid surrogate for overall survival (OS) in human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC), irrespective of disease stage, and in early-stage hormone receptor-positive (HR+)/HER2- BC. To advance the understanding of the association between additional DFS endpoints and OS, this study assessed the patient-level correlations between DFS and OS, invasive DFS (IDFS) and OS, and distant DFS (DDFS) and OS in Medicare beneficiaries with early-stage HER2- BC, overall and in subgroups of patients with HR+/HER2- BC and triple-negative BC (TNBC).

Methods: Patients with stages I-III HER2- BC aged ≥ 66 years were identified from SEER-Medicare data (2010-2019).

Estimation of Glyphosate biological half-life among farmers and residents in Thailand.

Glyphosate is a widely used herbicide worldwide. Research on human health effects has been limited and the toxicokinetics of glyphosate have not been widely examined. This research aimed to study the excretion profile and half-life of glyphosate in farmers and residents who use glyphosate to control weeds in their agricultural fields and near their households, respectively.

Development of an MRI Radiomic Machine-Learning Model to Predict Triple-Negative Breast Cancer Based on Fibroglandular Tissue of the Contralateral Unaffected Breast in Breast Cancer Patients.

Aim: The purpose of this study was to develop a radiomic-based machine-learning model to predict triple-negative breast cancer (TNBC) based on the contralateral unaffected breast's fibroglandular tissue (FGT) in breast cancer patients.

Materials And Methods: This study retrospectively included 541 patients (mean age, 51 years; range, 26-82) who underwent a screening breast MRI between November 2016 and September 2018 and who were subsequently diagnosed with biopsy-confirmed, treatment-naïve breast cancer. Patients were divided into training ( = 250) and validation ( = 291) sets.

Predictors of response to CDK4/6i retrial after prior CDK4/6i failure in ER+ metastatic breast cancer.

After disease progression on endocrine therapy (ET) plus a CDK4/6 inhibitor, there is no standardized sequence for subsequent treatment lines for estrogen receptor positive (ER+) metastatic breast cancer (MBC). CDK4/6i retrial as a treatment strategy is commonplace in modern clinical practice; however, the available prospective data investigating this strategy have had inconclusive results. To frame this data in a real-world context, we performed a retrospective analysis assessing the efficacy of CDK4/6is in 195 patients who had previous exposure to CDK4/6i in a prior treatment line at our institution.

Data from a survey of coffee cultivation in lowland and highland areas to support agriculture during climate change.

This survey aimed to acquire and generate significant information on coffee cultivation in high and low elevations to support agriculture during climate change. This survey dataset helps understand coffee cultivation in highland and lowland areas with diverse climates and environmental conditions for coffee researchers to use this data to improve cultivation and production techniques. In the business scope, this dataset provides a critical vision on the value proposition of the coffee business to maintain conservation and wealth creation of the coffee chain.

Tumor suppressor heterozygosity and homologous recombination deficiency mediate resistance to front-line therapy in breast cancer.

The co-occurrence of germline and somatic oncogenic alterations is frequently observed in breast cancer, but their combined biologic and clinical significance has not been evaluated. To assess the role of germline-somatic interactions on outcomes in routine practice, we developed an integrated clinicogenomic pipeline to analyze the genomes of over 4,500 patients with breast cancer. We find that germline (g) -associated tumors are enriched for loss-of-function mutations and manifest poor outcomes on standard-of-care, front-line CDK4/6 inhibitor (CDK4/6i) combinations.

A Novel Biomonitoring Method to Detect Pyrethroid Metabolites in Saliva of Occupationally Exposed Workers as a Tool for Risk Assessment.

Saliva is valuable in exposure assessment having been successfully used for drug and environmental pollutant detection, providing a surrogate measure of plasma concentrations. Pyrethroid biomarkers have not previously been assessed in saliva, although are prime candidates for saliva detection. This study's objectives were to 1) develop a liquid-liquid extraction (LLE) method to quantify six pyrethroid metabolites using gas chromatography/ion trap mass spectrometry and 2) assess its application for an occupationally exposed population.

Prevalence of Current Areca Nut Use and Its Associated Factors among Bhutanese Aged 15-69 Years: Analysis of the Nationally Representative STEPS Survey 2019.

Background: Areca nut (AN) use receives less global attention than tobacco use. Studies have linked AN consumption to a range of adverse health effects, including oral cavity and pharyngeal cancers, periodontal diseases, cardiovascular diseases, diabetes, hypertension, and addiction. The masticatory use of AN is rampant in Bhutan.

Pathologic complete response to KEYNOTE522 and HER2-directed therapy for synchronous TNBC and HER2+ breast cancer.

Simultaneous presentation of two separate primary breast cancers of differing histology at initial diagnosis is an uncommon phenomenon; it is even rarer to find these pathologically distinct populations within the same biopsy. Here we report the case of a patient diagnosed with clearly demarcated, pathologically heterogenous triple negative breast cancer (TNBC) and HER2+ breast cancer that was treated with a hybrid chemoimmunotherapy regimen combining elements of Keynote-522 and a standard HER2-directed neoadjuvant regimen, yielding apathologic complete response by the time of surgery with no notable adverse events. Molecular analysis of the histologically distinct tumor populations confirmed molecular evidence of differential HER2 expression but also suggested clonal relatedness of the two tumor populations based upon mutational profile, with phenotypic divergence potentially resulting from copy number alterations in NF1.

Pathologic complete response after neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers.

BRCA1 and BRCA2 pathogenic variant carriers develop breast cancers with distinct pathological characteristics and mutational signatures that may result in differential response to chemotherapy. We compared rates of pathologic complete response (pCR) after NAC between BRCA1/2 variant carriers and noncarriers in a cohort of 1426 women (92 [6.5%] BRCA1 and 73 [5.

FLT1 activation in cancer cells promotes PARP-inhibitor resistance in breast cancer.

Acquired resistance to PARP inhibitors (PARPi) remains a treatment challenge for BRCA1/2-mutant breast cancer that drastically shortens patient survival. Although several resistance mechanisms have been identified, none have been successfully targeted in the clinic. Using new PARPi-resistance models of Brca1- and Bard1-mutant breast cancer generated in-vivo, we identified FLT1 (VEGFR1) as a driver of resistance.

Invasive lobular breast cancer: Focus on prevention, genetics, diagnosis, and treatment.

Invasive lobular cancer (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast malignancies. The distinctive biological features of ILC include the loss of the cell adhesion molecule E-cadherin, which drives the tumor's peculiar discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. Typically, such tumors originate in the lobules, are more commonly bilateral compared to invasive ductal cancer (IDC) and require a more accurate diagnostic examination through imaging.

Intratumoral Fc-optimized agonistic CD40 antibody induces tumor rejection and systemic antitumor immunity in patients with metastatic cancer.

While CD40 agonism is an attractive approach for activating antigen-presenting cells and initiating antitumor responses, previous attempts have encountered limited clinical efficacy coupled with toxicity. We previously demonstrated that interactions between the antibody Fc domain and the inhibitory receptor FcγRIIB are critical for enhanced antitumor activity. Here, we present the results of a phase 1 study on intratumoral administration of an anti-CD40 agonistic antibody (2141-V11) Fc-engineered to enhance FcγRIIB binding.

Microparticles of arsenic water treatment media and water softener resin observed in treated water at private wells.

Observation of arsenic water treatment adsorption media in the treated water of several homes with high arsenic private wells led to the hypothesis that treatment media was escaping the treatment systems and entering the plumbing and drinking water. Our research at 62 homes identified that microparticles of arsenic water treatment media and/or water softener resin had escaped the treatment system in 71% of the homes. This is a potential health hazard as ingesting arsenic treatment media or water softener resin may lead to an elevated ingestion exposure to arsenic and other contaminants.

Dose dense doxorubicin plus cyclophosphamide in a modified KEYNOTE522 regimen for triple negative breast cancer.

The KEYNOTE-522 (KN522) regimen for neoadjuvant treatment of triple negative breast cancer (TNBC) utilized q3week dosing for doxorubicin plus cyclophosphamide (AC); however, dose-dense AC (ddAC) has demonstrated superior overall survival (OS) compared to q3week AC in anthracycline and taxane-based regimens. We performed a retrospective analysis assessing the use of ddAC in KN522 and the impact of sequencing ddAC before or after carboplatin/paclitaxel (CbT) plus pembrolizumab on multiple outcomes. 128 patients with TNBC were included.

Validation of a clinical breast cancer risk assessment tool combining a polygenic score for all ancestries with traditional risk factors.

Purpose: We previously described a combined risk score (CRS) that integrates a multiple-ancestry polygenic risk score (MA-PRS) with the Tyrer-Cuzick (TC) model to assess breast cancer (BC) risk. Here, we present a longitudinal validation of CRS in a real-world cohort.

Methods: This study included 130,058 patients referred for hereditary cancer genetic testing and negative for germline pathogenic variants in BC-associated genes.

Predictors of Response to CDK4/6i Retrial After Prior CDK4/6i Failure in ER+ Metastatic Breast Cancer.

After disease progression on endocrine therapy (ET) plus a CDK4/6 inhibitor, there is no standardized sequence for subsequent treatment lines for estrogen receptor positive (ER+) metastatic breast cancer (MBC). CDK4/6i retrial as a treatment strategy is commonplace in modern clinical practice; however, the available prospective data investigating this strategy have had inconclusive results. To frame this data in a real-world context, we performed a retrospective analysis assessing the efficacy of CDK4/6is in 195 patients who had previous exposure to CDK4/6i in a prior treatment line at our institution.

Active smoking in urban households: An association between urinary cotinine metabolite level and serum eGFR concentration.

Introduction: Smoking stands as a primary contributor to preventable deaths globally and is linked to an increased risk of developing kidney failure and other diseases. A few studies have focused on the negative correlation between serum cotinine and estimated glomerular filtration rate (eGFR), indicating decreased kidney function. This study investigated the associations between urinary cotinine metabolite concentration and serum eGFR among active smokers in urban households.

Effect of children secondhand smoke exposure associated with GABA concentration: Influence from parents who are extremely heavy smokers in urban households.

Background: Secondhand smoke (SHS) poses the most considerable health risk to children in urban households. However, limited evidence exists regarding the impact of children exposure to SHS on gamma-aminobutyric acid (GABA) levels. This study aimed to investigate the level of cotinine and GABA and their association with variables related to children exposed to SHS.