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.     

Personal comorbidities and their subsequent risks for liver,gallbladder and bile duct cancers

Many environmental risk factors for hepatobiliary cancers are known but whether they are associated with specific cancer types is unclear. We present here a novel approach of assessing standardized incidence ratios (SIRs) of previously diagnosed comorbidities for hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cholangiocarcinoma (CCA) and ampullary cancer. The 13 comorbidities included alcohol and nonalcohol related liver disease, chronic obstructive pulmonary disease, gallstone disease, viral and other kinds of hepatitis, infection of bile ducts, hepatic and other autoimmune diseases, obesity and diabetes. Patients were identified from the Swedish Inpatient Register from 1987 to 2018, and their cancers were followed from 1997 onwards. SIRs for HCC were 80 to 100 in men and women diagnosed with hepatitis C virus and they were also >10 in patients diagnosed with hepatitis B virus, other kind of hepatitis, hepatic autoimmune disease and nonalcohol related liver disease. Many of these risks, as well as alcohol related liver disease, were either specific to HCC or were shared with intrahepatic CCA. For GBC, CCA and ampullary cancer infection of bile ducts was the main risk factor. Gallstone disease, nonhepatic autoimmune diseases and diabetes were associated with all hepatobiliary cancers. The limitations of the study include inability to cover some rare risk factors and limited follow-up time. Many of the considered comorbidities are characterized by chronic inflammation and/or overt immune disturbance in autoimmune diseases. The results suggest that local chronic inflammation and a related immune disturbance is the carcinogenic trigger for all these cancers.     

Assessing the utility of yearly pre-season laboratory screening for athletes on a major professional sports team

Objectives

Professional athletes undergo annual pre-season laboratory screening, although clinical evidence supporting the practice is limited and no uniform set of guidelines on pre-season laboratory screening exists. The aim of this study was to assess the clinical value of annual pre-season laboratory screening tests for a major professional sports team over multiple years.

Selective reminding of prospective memory in Multiple Sclerosis

Objective: Multiple sclerosis (MS) is associated with prospective memory (PM) deficits, which may increase the risk of poor functional/health outcomes such as medication non-adherence. This study examined the potential benefits of selective reminding to enhance PM functioning in persons with MS.

Method: Twenty-one participants with MS and 22 healthy adults (HA) underwent a neuropsychological battery including a Selective Reminding PM (SRPM) experimental procedure. Participants were randomly assigned to either: (1) a selective reminding condition in which participants learn (to criterion) eight prospective memory tasks in a Selective Reminding format; or (2) a single trial encoding condition (1T).

Results: A significant interaction was demonstrated, with MS participants receiving greater benefit than HAs from the SR procedure in terms of PM performance. Across diagnostic groups, participants in the SR conditions (vs. 1T conditions) demonstrated significantly better PM performance. Individuals with MS were impaired relative to HAs in the 1T condition, but performance was statistically comparable in the SR condition.

Conclusions: This preliminary study suggests that selective reminding can be used to enhance PM cue detection and retrieval in MS. The extent to which selective reminding of PM is effective in naturalistic settings and for health-related behaviours in MS remains to be determined.     

Job hazards and respiratory symptoms in Hispanic female domestic cleaners

Abstract

The occupational hazards and respiratory symptoms of domestic cleaners in USA are largely unknown. We conducted a cross-sectional study among 56 Hispanic female domestic cleaner on their health status and frequency of cleaning products used and tasks performed. While women used multi-use products (60.0%) and toilet bowl cleaners (51.8%) most days of the week, many (39.3%) reported not using personal protective equipment while cleaning. Itchy/watery eyes (61.8%) and itchy nose (56.4%) were the most frequently reported symptoms. A history of physician-diagnosed asthma was reported by 14.3% while 33.9% had symptoms of bronchial hyperresponsiveness (BHR). In conclusion, this vulnerable population has high prevalence of physician-diagnosis asthma and BHR symptoms and is potentially exposed to myriad occupational hazards. Further research exploring associations between products use, cleaning tasks and respiratory symptoms is warranted.