Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.     

Reduction of ventricular arrhythmias with synchronized LV pacing—fact,fiction, or fortuitous

Journal of Interventional Cardiac Electrophysiology -     

CNS Maturation Process in Children and Adolescents in the Northern Region of the Russian Federation and Its Reflection in the Dynamics of Integral EEG Parameters

Neuroscience and Behavioral Physiology - We present here results from analysis of the formation of brain bioelectrical activity in children and adolescents living in the northern region of Russia...     

Dem eigenen Leben ein Ende setzen: Suizide zwischen Medizin und Ethik

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz -     

Bacterial and fungal co-infection is a major barrier in COVID-19 patients: A specific management and therapeutic strategy is required

Microbial co-infections are another primary concern in patients with coronavirus disease 2019 (COVID-19), yet it is an untouched area among researchers. Preliminary data and systematic reviews only show the type of pathogens responsible for that, but its pathophysiology is still unknown. Studies show that these microbial co-infections are hospital-acquired/nosocomial infections, and patients admitted to intensive care units with invasive mechanical ventilation are highly susceptible to it. Patients with COVID-19 had elevated inflammatory cytokines and a weakened cell-mediated immune response, with lower CD4⁺ T and CD8⁺ T cell counts, indicating vulnerability to various co-infections. Despite this, there are only a few studies that recommend the management of co-infections.     

Education Outcomes of Children Born Late Preterm: A Retrospective Whole-Population Cohort Study

Maternal and Child Health Journal - Early life exposures can have an impact on a child’s developmental trajectory and children born late preterm (34–36 weeks gestational age)...