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.     

The RECIST criteria compared to conventional response evaluation after peptide receptor radionuclide therapy in patients with neuroendocrine neoplasms

Annals of Nuclear Medicine - The Response Evaluation Criteria In Solid Tumors (RECIST) is the most used radiological method for evaluating response after peptide receptor radionuclide therapy...     

Influence of Prior Psychiatric Disorders on the Treatment Course of Gynaecological Cancer – A Nationwide Cohort Study

Aims

To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer.

Prevalence and Correlates of Mental Health Problems in Norwegian Peacekeepers 18–38 Years Postdeployment

Peacekeeping missions involve experiences that may impact the mental health of participating soldiers. However, research on the long-term mental health consequences of peacekeeping is sparse. The present study aimed to find the prevalence of mental health problems (MHPs), possible MHP predictors, and associations between predictors and MHPs in Norwegian peacekeepers 18–38 years after deployment to a United Nations peacekeeping mission. We used data from a cross-sectional, postdeployment survey of Norwegian peacekeepers who served in Lebanon between 1978 and 1998 (N = 10,605). Participants were assessed for posttraumatic stress disorder (PTSD); anxiety; depression; insomnia; alcohol misuse; drug misuse; and exposure to pre-, peri-, and postdeployment stressors. Logistic regressions were executed to explore key variables associated with MHPs. Total MHP prevalence was 15.1%, 95% CI [14.4, 15.8]. The estimates for specific disorders were 0.1% for drug misuse, 3.4% for alcohol misuse, 4.0% for depression, 6.2% for PTSD, 6.4% for anxiety, and 9.3% for insomnia. Postdeployment stressors, OR = 1.91, 95% CI [1.79, 2.04]; employment status, OR = 1.41, 95% CI [1.33, 1.48]; and traumatic exposure during deployment, OR = 1.11, 95% CI [1.09, 1.12], were positively related to PTSD, χ2(17, N = 8,568) = 1,791.299, p < .001. Similar patterns were found for the other MHPs. Considering that most participants (84.9%) reported low symptom levels, our findings challenge the widespread public perception that most peacekeepers have MHPs. Moreover, our results indicate that future peacekeepers should be prepared for challenges they may face not only during deployment but also in the years following their homecoming.     

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.