Pandemic-Proofing: Intercepting Zoonotic Spillover Events.

Zoonotic spillover events pose a significant and growing threat to global health. By focusing on preventing these cross-species transmissions, we can significantly mitigate pandemic risks. This review aims to analyze the mechanisms of zoonotic spillover events, identify key risk factors, and propose evidence-based prevention strategies to reduce future pandemic threats.

Current and emerging strategies for the prevention of hepatocellular carcinoma.

Liver cancer is the third leading cause of cancer-related deaths globally, with incident cases expected to rise from 905,700 in 2020 to 1.4 million by 2040. Hepatocellular carcinoma (HCC) accounts for about 80% of all primary liver cancers.

Reprogramming SREBP1-dependent lipogenesis and inflammation in high-risk breast with licochalcone A: a novel path to cancer prevention.

Background: Anti-estrogens have had limited impact on breast cancer (BC) prevention. Novel agents with better tolerability, and efficacy beyond estrogen receptor (ER) positive BC are needed. We studied licochalcone A (LicA) for ER-agnostic BC prevention.

Effect of Time-Restricted Eating on Circulating Levels of IGF1 and Its Binding Proteins in Obesity: An Exploratory Analysis of a Randomized Controlled Trial.

Unlabelled: Obesity is associated with alterations in circulating IGF1, IGF1-binding proteins (IGFBPs), insulin, inflammatory markers, and hormones implicated in cardiovascular disease, diabetes, cancer, and aging. However, the effects of 4 and 6 h time-restricted eating (TRE) on circulating IGF1 and IGFBPs is uncertain.

Objective: This study aimed to investigate the effects of TRE on plasma IGF1, IGFBP1, IGFBP2, and IGFBP3, and whether these effects were mediated by weight loss or body composition changes.

Overcoming challenges in conducting early phase breast cancer prevention trials: Bazedoxifene and conjugated estrogens vs waitlist control.

Background: The combination of bazedoxifene 20 mg (BZA) and conjugated estrogens 0.45 mg (CE) marketed as Duavee® is approved for vasomotor symptom relief and osteoporosis prevention. Our pilot study suggested it had potential breast cancer risk reduction, and we proposed a multisite Phase IIB primary prevention trial assessing change in breast imaging and tissue risk biomarkers.

Northwestern University resource and education development initiatives to advance collaborative artificial intelligence across the learning health system.

Introduction: The rapid development of artificial intelligence (AI) in healthcare has exposed the unmet need for growing a multidisciplinary workforce that can collaborate effectively in the learning health systems. Maximizing the synergy among multiple teams is critical for Collaborative AI in Healthcare.

Methods: We have developed a series of data, tools, and educational resources for cultivating the next generation of multidisciplinary workforce for Collaborative AI in Healthcare.

Ductal carcinoma in situ of the breast: finding the balance between overtreatment and undertreatment.

Ductal carcinoma in situ (DCIS) accounts for 15-25% of all breast cancer diagnoses. Its prognosis is excellent overall, the main risk being the occurrence of local breast events, as most cases of DCIS do not progress to invasive cancer. Systematic screening has greatly increased the incidence of this non-obligate precursor of invasion, lending urgency to the need to identify DCIS that is prone to invasive progression and distinguish it from non-invasion-prone DCIS, as the latter can be overdiagnosed and therefore overtreated.

A randomized Phase I pre-operative window trial of transdermal endoxifen in women planning mastectomy: Evaluation of dermal safety, intra-mammary drug distribution, and biologic effects.

Breast cancer prevention only requires local exposure of the breast to active drug. However, oral preventive agents entail systemic exposure, causing adverse effects that limit acceptance by high-risk women. Drug-delivery through the breast skin is an attractive option, but requires demonstration of dermal safety and drug distribution throughout the breast.

Current status and challenges of breast cancer prevention~DNA methylation would lead to groundbreaking progress in breast cancer prevention~.

The number of breast cancer patients is increasing worldwide. Furthermore, breast cancer often develops in young people, even those only in their 30s, who play a central role in their families and society. Results from many cohort studies suggest that dietary factors, alcohol consumption, lack of physical activity, obesity, nulliparity, breastfeeding, oral contraceptive use, fertility treatment and hormone replacement therapy are risk factors for breast cancer.

Presurgical Oral Tamoxifen vs Transdermal 4-Hydroxytamoxifen in Women With Ductal Carcinoma In Situ: A Randomized Clinical Trial.

Importance: Oral tamoxifen citrate benefits women with ductal carcinoma in situ (DCIS), but concern about toxic effects has limited acceptance. Previous pilot studies have suggested transdermal 4-hydroxytamoxifen gel has equivalent antiproliferative efficacy to oral tamoxifen, with low systemic exposure.

Objective: To demonstrate that 4-hydroxytamoxifen gel applied to the breast skin is noninferior to oral tamoxifen in its antiproliferative effect in DCIS lesions.

The impact of histologic subtype on primary site surgery in the management of metastatic lobular versus ductal breast cancer: a population based study from the National Cancer Database (NCDB).

Purpose: Primary site surgery for metastatic breast cancer improves local control but does not impact overall survival. Whether histologic subtype influences patient selection for surgery is unknown. Given differences in surgical management between early-stage lobular versus ductal disease, we evaluated the impact of histology on primary site surgery in patients with metastatic breast cancer.

Breast Cancer Risk Reduction: Current Status and Emerging Trends to Increase Efficacy and Reduce Toxicity of Preventive Medication.

The primary prevention of breast cancer is a worthwhile goal for which the efficacy of antiestrogens is well established. However, implementation has been problematic related to low prioritization by providers and the reluctance of high-risk women to experience medication side effects. Emerging solutions include improved risk estimation through the use of polygenic risk scores and the application of radiomics to screening mammograms; and optimization of medication dose to limit toxicity.

Phase Ib trial of inhaled iloprost for the prevention of lung cancer with predictive and response biomarker assessment.

Introduction: Iloprost, a prostacyclin analog, has lung cancerpreventive activity in preclinical models and improved dysplasia in former smokers in a phase IIb trial. Oral iloprost is currently unavailable. We performed a phase Ib trial of inhaled iloprost in former smokers to assess tolerance and compliance.

The impact of histologic subtype on primary site surgery in the management of metastatic lobular versus ductal breast cancer: a population based study from the National Cancer Database.

Purpose: Primary site surgery for metastatic breast cancer improves local control but does not impact overall survival. Whether histologic subtype influences patient selection for surgery is unknown. Given differences in surgical management between early-stage lobular versus ductal disease, we evaluated the impact of histology on primary site surgery in patients with metastatic breast cancer.

Identification of metabolic pathways contributing to ER breast cancer disparities using a machine-learning pipeline.

African American (AA) women in the United States have a 40% higher breast cancer mortality rate than Non-Hispanic White (NHW) women. The survival disparity is particularly striking among (estrogen receptor positive) ER breast cancer cases. The purpose of this study is to examine whether there are racial differences in metabolic pathways typically activated in patients with ER breast cancer.

Breast cancer prevention with liquiritigenin from licorice through the inhibition of aromatase and protein biosynthesis in high-risk women's breast tissue.

Breast cancer risk continues to increase post menopause. Anti-estrogen therapies are available to prevent postmenopausal breast cancer in high-risk women. However, their adverse effects have reduced acceptability and overall success in cancer prevention.

Inhibition of primary and secondary nucleation alongwith disruption of amyloid fibrils and alleviation of associated cytotoxicity: A biophysical insight of a novel property of Chlorpropamide (an anti-diabetic drug).

Aggregation of physiologically synthesized soluble proteins to insoluble, cytotoxic fibrils is a pre-requisite for pathogenesis of amyloid associated disorders including Alzheimer's disease, non-systemic amyloidosis, Parkinson's disease, etc. Considerable advancement has been made to understand the mechanism behind aggregation process but till date we have no efficient cure and preventive therapy for associated diseases. Strategies to prevent protein aggregation are nevertheless many which have been proved promisingly successful in vitro.

Z-Endoxifen prevents aggressive mammary cancers in mice by inhibiting cell proliferation and creating a tumor suppressive microenvironment.

Aggressive estrogen receptor (ER) positive breast cancer is frequently tamoxifen-resistant; alternative endocrine approaches exist for therapy, but not for prevention, particularly in premenopausal women. We examined the efficacy of the selective ER modulator (Z-endoxifen) as monotherapy and in combination with the selective progesterone receptor modulators (onapristone and ulipristal acetate) in the tamoxifen-insensitive C3(1)/SV40TAg mouse mammary tumorigenesis model. Unlike tamoxifen at human equivalent dose (HED) 101 mg/day, endoxifen at HED 24 mg/day significantly increased latency and reduced tumor growth relative to untreated controls.

Menstrual Phase and Menopausal Status Classification of Benign Breast Tissue Using Hormone-Regulated Gene Expression and Histomorphology: A Validation Study.

Background: The validation of breast cancer risk biomarkers in benign breast samples (BBS) is a long-sought goal, hampered by the fluctuation of gene and protein expression with menstrual phase (MP) and menopausal status (MS). Previously, we identified hormone-related gene expression and histomorphology parameters to classify BBS by MS/MP. We now evaluate both together, to validate our prior results.

Longitudinal Sedentary Time and Symptoms in Breast Cancer Patients during Chemotherapy Using Ecological Momentary Assessment.

Purpose: To examine the relationship between daily fluctuations in symptoms and sedentary behavior (SB) during chemotherapy (CT) for breast cancer.

Methods: Breast cancer patients ( N = 68, M age = 48.5 ± 10.

Towards the development of DCIS risk prediction models.

Ductal carcinoma in situ (DCIS) has a variable natural history, with a poorly understood biology. In this issue of Cancer Cell, Strand et. al.