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.     

Effects of anteriorly-loaded treadmill walking on dynamic gait stability in young adults

BackgroundAnteriorly-loaded walking is common in many occupations and may increase fall risk. Dynamic gait stability, defined by the Feasible Stability Region (FSR) theory, quantifies the kinematic relationship between the body’s center of mass (COM) and base of support (BOS). FSR-based dynamic gait stability has been used to evaluate the fall risk.Research questionHow does front load carriage affect dynamic gait stability, step length, and trunk angle among young adults during treadmill walking?MethodsIn this between-subject design study, 30 healthy young adults were evenly randomized into three load groups (0%, 10%, or 20% of body weight). Participants carried their assigned load while walking on a treadmill at a speed of 1.2 m/s. Body kinematics were collected during treadmill walking. Dynamic gait stability (the primary variable) was calculated for two gait events: touchdown and liftoff. Step length and trunk angle were measured as secondary variables. One-way analysis of variance was conducted to detect any group-related differences for all variables. Post-hoc analysis with Bonferroni correction was performed when main group differences were found.ResultsNo significant differences but medium to large effect sizes were found between groups for dynamic gait stability at touchdown (p = 0.194, η² = 0.114) and liftoff (p = 0.122, η² = 0.139). Trunk angle significantly increased (indicating backward lean) with the front load at touchdown (p < 0.001, η² = 0.648) and liftoff (p < 0.001, η² = 0.543). No significant between-group difference was found related to the step length (p = 0.344, η² = 0.076).SignificanceCarrying a front load during walking significantly alters the trunk orientation and may change the COM-BOS kinematic relationship and, therefore, fall risk. The findings could inform the design of future studies focusing on the impact of anterior load carriage on fall risk during different locomotion.     

Hypofractionated radiation therapy for invasive breast cancer: From moderate to extreme protocols

Adjuvant irradiation is the standard treatment after breast conservative surgery. Normofractionated regimen with an overall treatment time of 5 to 6 weeks is often considered as a limiting factor for irradiation compliance. In order to answer this issue, moderate and more recently extreme hypofractionated protocols appeared. We report here oncological outcomes and toxicity of hypofractionated breast irradiation. After defining the frame of moderate and extreme hypofractionated breast irradiations based on overall treatment time, patient selection criteria were listed. According to their levels of proof, the results of moderate and extreme hypofractionated breast irradiation were analysed. Overall treatment time for moderate hypofractionated breast irradiation ranged from 3 to 4 weeks, while for extreme hypofractionated breast irradiation, it was less than 1 week. For moderate hypofractionated breast irradiation, whole breast irradiation was currently performed with or without lymph node irradiation. Moderate hypofractionated breast irradiation has proven to be as safe and as efficient as normofractionated breast irradiation with level IA evidence. For extreme hypofractionated breast irradiation, phase III randomized trials confirmed that accelerated partial breast irradiation was non-inferior in terms of local control compared to normofractionated whole breast irradiation (with external beam radiation therapy and multicatheter brachytherapy), with similar acute and late toxicity. While the use of intraoperative breast irradiation remains under debate, new very accelerated partial breast irradiation (overall treatment time not exceeding 2 days) protocols emerged with encouraging results. Accelerated partial breast irradiation is warranted for extreme hypofractionated breast irradiation and is indicated for low-risk breast cancers. Moderate and extreme hypofractionated breast irradiation regimens are validated and can be routinely proposed according to patient selection criteria.     

论当前疾病预防控制体系面临的主要问题

对当前的疾病预防控制体系和机构面临的体系不健全、政府投入不充分、事业发展不平衡、人才缺失和能力不足、缺乏系统的理论指导、体系的碎片化严重、与社会经济发展的战略衔接不力、机构内部内生动力和活力不足以及体系治理能力不足等问题做了讨论分析,以期进一步分析在健康中国战略和事业单位机构改革等宏观环境变化所带来的机遇以及疾控体系的发展策略和具体措施,促进疾病预防控制事业在改革中谋发展。     

Losing the uphill battle? Emergent harm reduction interventions and barriers during the opioid overdose crisis in Canada

Canada continues to experience an escalating opioid overdose crisis that has claimed more than 8000 lives in the country since 2016. The presence of the synthetic opioid fentanyl and its analogues is a central contributor to the increases in preventable opioid-related deaths. However, a number of converging social-structural factors (e.g., the continued criminalisation of drug use, political changes) and political barriers are also complicating and contributing to the current crisis. We briefly outline four harm reduction interventions (i.e., injectable opioid agonist treatment, naloxone distribution programs, overdose prevention sites, and drug checking services) as emerging and rapidly expanding responses to this crisis in Canada. These examples of innovation and expansion are encouraging but also occurring at the same time that the opioid overdose crisis shows few signs of abating. To truly address the crisis, Canada needs political environments at all government levels that are responsive and foster harm reduction innovation and drug policy experimentation.     

Outcomes after neoadjuvant or adjuvant chemotherapy for cT2-4N0-1 non–small cell lung cancer: A propensity-matched analysis

Objective

Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.