IMPORTANCE The role of endogenous progesterone in the development of breast cancer remains largely unexplored to date, primarily owing to assay sensitivity limitations and low progesterone concentrations in postmenopausal women. Recently identified progesterone metabolites may provide insights as experimental data suggest that 5α-dihydroprogesterone (5αP) concentrations reflect cancer-promoting properties and 3α-dihydroprogesterone (3αHP) concentrations reflect cancer-inhibiting properties. OBJECTIVE To evaluate the association between circulating progesterone and progesterone metabolite levels and breast cancer risk. DESIGN, SETTING, AND PARTICIPANTS Using a sensitive liquid chromatography-tandem mass spectrometry assay, prediagnostic serum levels of progesterone and progesterone metabolites were quantified in a case-cohort study nested within the Breast and Bone Follow-up to the Fracture Intervention Trial (n = 15 595). Participation was limited to women not receiving exogenous hormone therapy at the time of blood sampling (1992-1993). Incident breast cancer cases (n = 405) were diagnosed during 12 follow-up years and a subcohort of 495 postmenopausal women were randomly selected within 10-year age and clinical center strata. Progesterone assays were completed in July 2017; subsequent data analyses were conducted between July 15, 2017, and December 20, 2018. EXPOSURES Circulating concentrations of pregnenolone, progesterone, and their major metabolites. MAIN OUTCOMES AND MEASURES Development of breast cancer, with hazard ratios (HRs) and 95% CIs was estimated using Cox proportional hazards regression adjusted for key confounders, including estradiol. Evaluation of hormone ratios and effect modification were planned a priori. RESULTS The present study included 405 incident breast cancer cases and a subcohort of 495 postmenopausal women; the mean (SD) age at the time of the blood draw was 67.2 (6.2) years.

Frequent detection of serous tubal intraepithelial carcinoma (STIC) among BRCA1/2 mutation carriers undergoing risk-reducing surgery prompted the hypothesis that many adnexal high-grade serous carcinomas (HGSCs) arise from the fallopian tube, rather than the ovary, as supposed. The changing paradigm has important implications for HGSC prevention. Most data related to the frequency of STIC are derived from case series and estimates vary widely. Therefore, we analyzed population-based data from 10 523 surgeries including salpingectomy (Jan 2014–Dec 2016) that were examined using the “Sectioning and Extensively Examining the Fimbria” protocol, which optimizes STIC detection. Overall, STIC was detected in 40 (0.38%) specimens, including 32 diagnosed with concurrent gynecologic cancer. STIC was detected in 8 (<0.01%) of 9392 cases with benign diagnoses. We conclude that the relative rarity of STIC diagnoses in routine pathology practice has critical implications for research aiming to elucidate the pathogenesis of HGSC and developing prevention strategies.

Background Safety climate is an upstream predictor of safety behaviors (e.g., safety compliance), organizational outcomes (e.g., burnout, engagement), and safety outcomes (e.g., injuries). The Fire Service Organizational Culture of Safety (FOCUS) survey, which was psychometrically validated, measures the industry-specific safety climate of the US fire and rescue service. It is expressed by two factors, Management Commitment to Safety and Supervisor Support for Safety. Methods The FOCUS beta-test included a random sample of 132 fire departments stratified by Federal Emergency Management Agency region and organization type (career, combination, volunteer). We conducted descriptive analysis with the responses from 8414 firefighters nested within 611 stations in 125 fire departments. We reported descriptive statistics to assess the distribution of all continuous [mean ± standard deviation (SD)] and categorical variables (counts, percentages) stratified by organization type. Regression analyses were conducted to investigate the associations between safety climate, safety behaviors, organizational outcomes, and safety outcomes stratified by organization type. Results The mean age of the analytic sample was 40.2 years, and the mean years of experience was 16.1 years. This sample included 53.6% career, 27.2% combination (career and volunteer), and 19.2% volunteer fire departments. The mean Management Commitment score was 71.4 (SD =  ± 10.4), and the mean Supervisor Support score was 81.7 (± 5.2). The mean Management Commitment scores were 67.1 (± 8.4), 72.2 (± 10.7), and 82.1 (± 6.1), respectively, for career, combination, and volunteer fire departments. The mean Supervisor Support scores were not notably different by organization type. Regression analyses generally supported the beneficial role of safety climate, while suggesting organization type as a potential effect modifier. Specifically, we observed a more negative association between Management Commitment as departments became more career. Conclusions Analysis of nationally representative data from the US fire and rescue service indicates safety climate is positively associated with safety behavior, organizational outcomes, and safety outcomes reflecting employee well-being. The findings also suggest that this association varies by organization type. In fact, a dose–response relationship was observed, with Management Commitment to safety lowest among career departments. Thus, our results suggest that it is not just being busy that decreases Management Commitment.

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