Search

The absence of effective therapeutic targets and aggressive nature of triple-negative breast cancer (TNBC) renders this disease subset difficult to treat. Although estrogen receptor beta (ERβ) is expressed in TNBC, studies on its functional role have yielded inconsistent results. However, recently, our preclinical studies, along with other observations, have shown the potential therapeutic utility of ERβ in the context of mutant p53 expression. The current case study examines the efficacy of the selective estrogen receptor modulator tamoxifen in p53-mutant TNBC with brain metastases. Significant increase in ERβ protein expression and anti-proliferative interaction between mutant p53 and ERβ were observed after cessation of tamoxifen therapy, with significant regression of brain metastases. This case study provides supporting evidence for the use of tamoxifen in p53-mutant, ERβ+TNBC, especially in the setting of brain metastasis.

Patients taking adjuvant endocrine therapy (AET) after breast cancer face adherence challenges and symptom-related distress. We conducted a randomized trial to evaluate the feasibility, acceptability, and preliminary efficacy of a telehealth intervention (Symptom-Targeted Randomized Intervention for Distress and Adherence to Adjuvant Endocrine Therapy [STRIDE]) for patients taking AET.From October 2019 to June 2021, 100 patients reporting difficulty with AET were randomly assigned to either STRIDE or a medication monitoring (MedMon) control group. STRIDE included six weekly small-group videoconferencing sessions and two individual calls. We defined feasibility as having50% of eligible patients enroll,70% complete the 12-week assessment, and 70% of STRIDE patients complete ≥4/6 sessions. We monitored adherence with the Medication Event Monitoring System Caps (MEMS Caps). At baseline and 12- and 24-weeks after baseline, patients self-reported adherence (Medication Adherence Report Scale), AET satisfaction (Cancer Therapy Satisfaction Questionnaire), symptom distress (Breast Cancer Prevention Trial-Symptom Checklist), self-management of symptoms (Self-efficacy for Symptom Management-AET), coping (Measure of Current Status), quality of life (QOL; Functional Assessment of Cancer Therapy-Breast), and mood (Hospital Anxiety and Depression Scale). We used linear mixed effects models to assess the effect of STRIDE on longitudinal outcomes.We enrolled 70.9% (100/141) of eligible patients; 92% completed the 12-week assessment, and 86% completed ≥4/6 STRIDE sessions. Compared with MedMon, STRIDE patients reported less symptom distress (B[difference] = -1.91; 95% CI, -3.29 to -0.52; p = .007) and better self-management of AET symptoms, coping, QOL, and mood. We did not observe significant differences in AET satisfaction or adherence.STRIDE is feasible and acceptable, showing promise for improving outcomes in patients taking AET after breast cancer.Patients taking adjuvant endocrine therapy (AET) after breast cancer may face challenges while following their treatment regimen. In this randomized controlled trial of 100 patients taking AET, a brief, small-group virtual intervention (STRIDE) was well-received by patients and led to improvements in how upset patients were due to symptoms, how confident they were in managing symptoms, and how well they could cope with stress. Thus, STRIDE is a promising intervention and should be tested in future multi-site trials.

Most patients report pain while taking adjuvant endocrine therapy (AET) for the treatment of breast cancer. While studies have examined patients' experiences with side effects, none solely capture patients' experiences with AET-related pain, a troubling symptom that reduces quality of life and impairs treatment adherence. This study explored themes of AET-related pain to inform future intervention development.Between November 2017 and November 2018, female patients (n = 30) with early-stage breast cancer enrolled between 3 and 36 months post-initiation of AET. Purposeful sampling was stratified by adherence level, age, distress level and time taking AET. Study staff conducted, transcribed and coded semi-structured interviews via inductive thematic coding to identify pain-related themes and achieved high inter-coded reliability (Kappa = 0.96).Several pain-related themes were observed. Attitudes around pain are generally negative, and management needs are largely unmet. Patients reported preferences for non-pharmacological management strategies and cited AET pain as a reason for medication breaks but not discontinuation. Patients within 19 months of starting AET and low adherers reported more intense and disruptive pain.Patients' experiences varied by patient attributes and revealed modifiable factors that may be targeted through behavioural interventions. AET-related pain is a complex side effect for which psychosocial support may be beneficial.

This study’s purpose was to determine the feasibility of a nurse coached walking intervention for informal caregivers of persons with dementia. Participants were randomly assigned to a nurse coached intervention or a control group. Five male and 27 female caregivers ( n = 32) participated. Measures included steps, walked well-being, and perceived stress. For steps walked, each group experienced a statistical difference ( p = .01 control; p = .02 intervention) and large effect size (0.90). Neither group had a statistical difference in well-being ( p = .38 control; p = .08 intervention) or perceived stress ( p = .56 control; p = .18 intervention). The intervention group achieved a large effect size in well-being (1.38) and moderate effect size in perceived stress (0.51). A 0.94 pedometer adherence, self-reported user ease with technology and 100% retention rate support feasibility. Many participants described feelings of loneliness and grief, but reported the pedometer motivated them to walk.

Purpose: Adjuvant endocrine therapy (AET) prevents recurrence after early-stage, hormone sensitive breast cancer; however, adherence to AET is suboptimal, and efficacious interventions are severely lacking. Barriers to adherence are well established; however, interventions thus far have failed to produce meaningful changes in adherence and have generally not followed guiding principles of psychosocial intervention development. The purpose of this paper is to describe the iterative development, using the National Institutes of Health Stage Model for Behavioral Intervention Development, of an evidence-based, patient-centered, telehealth intervention to enhance adherence, improve symptom management, and reduce distress for patients taking AET after breast cancer, with a focus on 1) a small open pilot study which informed modifications and refinement of the intervention based on quantitative and qualitative patient feedback about feasibility and acceptability; and 2) the underlying theoretical and empirical rationale for each component of the finalized intervention. Clinical implications and directions for future research are discussed.

BackgroundCurrent research indicates that structured yoga practice may improve physical and emotional symptoms related to cancer treatment. Yoga is recommended for patients with cancer, yet there are barriers to participation in community- and hospital-based classes. Wellness interventions such as yoga are easy to access via the internet, but information can be overwhelming and not tailored to people with cancer.PurposeThe purpose of this study was to develop a nurse-led, breast cancer-specific, web-based gentle yoga video for home use, and to understand the feasibility, utilization, and safety of the video in a sample of breast cancer survivors.MethodData was collected via open-ended telephone interviews three times over a 4-week period.ResultsThe 14 women participating in the study reported that the web-based video was safe in that it resulted in no injury, and was easy to use, and convenient to access. However, most did not continue to practice the video for the full 4 weeks of the study. A knowledge deficit about gentle yoga as a structured mindful movement-based practice rather than a vigorous exercise was identified.ImplicationsNurses can provide tailored wellness interventions for cancer survivors via video stream. Future work should include instruction that yoga is a mindfulness-based self-care activity requiring regular practice.

Background Research biopsies (RBs) are essential to understanding tumor biology and mechanisms of resistance and to advancing precision medicine. However, RBs have associated risks and may not benefit the patient. Objectives The purpose of this integrative review is to summarize and synthesize the current literature on the experience, attitudes, and understanding of patients with cancer related to RBs. Methods Articles from January 2010 to February 2017 were retrieved via a search of MEDLINE®. Articles included reported on the willingness, perceptions, understanding, attitudes, and/or experience of patients with cancer related to RBs. Findings Nine of 216 identified studies were selected. Studies exploring patient willingness to undergo RBs (n = 6) identified RBs as a potential barrier to clinical trial participation. Studies exploring patient understanding and informed consent (n = 3) revealed variable patient knowledge of the risks and benefits of RBs.

Functional variomics provides the foundation for personalized medicine by linking genetic variation to disease expression, outcome and treatment, yet its utility is dependent on appropriate assays to evaluate mutation impact on protein function. To fully assess the effects of 106 missense and nonsense variants of PTEN associated with autism spectrum disorder, somatic cancer and PTEN hamartoma syndrome (PHTS), we take a deep phenotypic profiling approach using 18 assays in 5 model systems spanning diverse cellular environments ranging from molecular function to neuronal morphogenesis and behavior. Variants inducing instability occur across the protein, resulting in partial-to-complete loss-of-function (LoF), which is well correlated across models. However, assays are selectively sensitive to variants located in substrate binding and catalytic domains, which exhibit complete LoF or dominant negativity independent of effects on stability. Our results indicate that full characterization of variant impact requires assays sensitive to instability and a range of protein functions., Mutations in PTEN have been associated with various human disease, including autism spectrum disorder (ASD) and cancer. Here, the authors assess the function of 106 PTEN variants in yeast, invertebrate models and cell culture and report that PTEN variants generally decrease protein stability.

Research Biopsies in Oncology – Patient Willingness, Perceptions, Understanding, and Experience: An Integrative Review. Background Tumors are classified into subsets based on molecular alterations to select personalized therapies, and research biopsies are essential to advance personalized medicine. However, research biopsies can be associated with complications, results might not directly benefit the patient particularly on-treatment biopsies obtained for evaluation of pharmacodynamics effect, and mandatory requirement can impact patient enrollment in clinical trials. Understanding patient perceptions and experiences surrounding research biopsies may highlight areas for improvement and could expand participation in clinical trials. Objectives The purpose of this integrative review explores and summarizes the current literature on oncology patient perceptions, willingness and experience of research biopsies evaluates data to determine potential implications for practice improvement, patient experience, and clinical trial participation. Methods Articles from January 2010-February 2016 were retrieved via a systematic search restricted to English of MEDLINE/Ovid. Search terms included breast cancer, cancer, research, biopsy, perceptions and attitudes. Inclusion criteria were studies that included patients with cancer and had information on patient willingness, perceptions, understanding, attitudes, and/or experience around research biopsies. Abstracts were independently reviewed for inclusion by two authors. For each selected manuscript, the following information was abstracted: primary author, sample and setting, results, conclusion, and assessment of strength of evidence level and quality using John Hopkins Nursing Evidence Based Practice (JHNEBP) Rating Scales. Results The search resulted in 175 unique studies. 17 abstracts were selected for full manuscript review. From these, 8 were excluded for not meeting inclusion criteria. The 9 selected studies ranged in sample size from 10-362 and all articles were rated IIIA-B evidence level. The majority of studies (66.7%) focused on breast cancer patients. Studies exploring patient willingness to undergo research biopsies (N=8) revealed variability in patient willingness to undergo research biopsies and identified research biopsies identified as a potential barrier to clinical trial participation. Studies exploring patient understanding of the risks and benefits of research biopsies (N=3) revealed overall poor understanding among patients. One study explored anxiety surrounding the research biopsy procedure, suggesting significant anticipatory anxiety is a significant concern. Issues surrounding informed consent were raised in several studies. Conclusions Research biopsies can be associated with significant anxiety, potentially impact enrollment in clinical trials, and consequently there is a need for development of strategies to improve patient experience and education. While a separate consent for research biopsies may be onerous, tailored educational materials, focus groups, as well as development of alternate strategies such as liquid biopsies, are essential to ensuring advancement in cancer care and outcomes. Key Words: cancer, research, biopsy, perceptions, attitudes. Citation Format: Abraham E, Spring L, D'Alleva J, Malvarosa G, Tripp E, Post K, Bardia A, Habin K. Research biopsies in oncology-patient willingness, perceptions, understanding, and experience: An integrative review [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-20-07.

PURPOSE/OBJECTIVES To describe the experience of women with estrogen receptor-positive breast cancer who are initiating oral adjuvant therapy and to determine what they describe as facilitating and/or hindering this experience. . RESEARCH APPROACH Qualitative inquiry. . SETTING Massachusetts General Hospital Cancer Center in Boston. . PARTICIPANTS 14 women aged 48-81 years. . METHODOLOGIC APPROACH Qualitative, descriptive study using content analysis. . FINDINGS Five themes were identified. CONCLUSIONS Each participant who was initiating oral adjuvant treatment described many unmet needs. Women who were caregivers, were older aged, had several chronic illnesses, and were on several medications reported more difficulty transitioning to oral adjuvant therapy. . INTERPRETATION This study suggests that nurses need to collaborate with other members of the healthcare team to assess the needs of and provide comprehensive care to women initiating oral adjuvant therapy. This is particularly true for women who are older aged, self-reported caregivers, and on several medications, and who have chronic comorbid conditions.

Caregivers of persons with dementia demonstrate increased levels of stress, anxiety and depression, placing them at increased risk for poor health-related outcomes. Walking is widely supported as a cost-effective, accessible exercise and way to maintain physical fitness and mitigate stress levels. There is a critical gap in addressing health promotion strategies in caregivers. The specific aims of this health-coaching (HC) walking study using wireless pedometers in family caregivers of persons with dementia were to: 1) establish the feasibility of HC and wireless pedometer use, 2) examine outcomes of well-being, stress and activity level and 3) understand the experience of participation. This 2-group comparative study used a repeated measure design and mixed methods approach. We enrolled 27 females and 5 male caregivers (n=32), μ age 57 years: with both 16 in the control in the intervention arm. Pre-post measures of general health (body mass index [BMI], blood pressure, heart rate, cognition, well-being, stress and perceived activity level) were obtained from caregivers at baseline and again at 12 weeks. Results indicate that those who received HC had a statistically significant improvement in BMI (p = .01). There were no other statistically significant improvements in outcomes in either group. Qualitative findings suggest that participants reported many stresses that made self-care challenging. In summary, this was a feasible intervention that resulted in improved BMI in the HC group. Work is needed to understand the long-term impact of this outcome. Further exploration of other health-promoting interventions that may be beneficial for this population is essential.

Oxidative stress is a common feature of the aging process and of many neurodegenerative disorders, including Alzheimer's disease. Understanding the direct causative relationship between oxidative stress and amyloid pathology, and determining the underlying molecular mechanisms is crucial for the development of more effective therapeutics for the disease. By employing microdialysis technique, we report local increase in the amyloid-β42 levels and elevated amyloid-β42/40 ratio in the interstitial fluid within 6 h of direct infusion of oxidizing agents into the hippocampus of living and awake wild type mice. The increase in the amyloid-β42/40 ratio correlated with the pathogenic conformational change of the amyloid precursor protein-cleaving enzyme, presenilin1/γ-secretase. Furthermore, we found that the product of lipid peroxidation 4-hydroxynonenal, binds to both nicastrin and BACE, differentially affecting γ- and β-secretase activity, respectively. The present study demonstrates a direct cause-and-effect correlation between oxidative stress and altered amyloid-β production, and provides a molecular mechanism by which naturally occurring product of lipid peroxidation may trigger generation of toxic amyloid-β42 species.

Background Synaptic loss strongly correlates with memory deterioration. Local accumulation of amyloid β (Aβ) peptide, and neurotoxic Aβ42 in particular, due to abnormal neuronal activity may underlie synaptic dysfunction, neurodegeneration, and memory impairments. To gain an insight into molecular events underlying neuronal activity-regulated Aβ production at the synapse, we explored functional outcomes of the newly discovered calcium-dependent interaction between Alzheimer’s disease-associated presenilin 1 (PS1)/γ-secretase and synaptic vesicle proteins. Results Mass spectrometry screen of mouse brain lysates identified synaptotagmin 1 (Syt1) as a novel synapse-specific PS1-binding partner that shows Ca2+-dependent PS1 binding profiles in vitro and in vivo. We found that Aβ level, and more critically, conformation of the PS1 and the Aβ42/40 ratio, are affected by Syt1 overexpression or knockdown, indicating that Syt1 and its interaction with PS1 might regulate Aβ production at the synapse. Moreover, β-secretase 1 (BACE1) stability, β- and γ-secretase activity, as well as intracellular compartmentalization of PS1 and BACE1, but not of amyloid precursor protein (APP), nicastrin (Nct), presenilin enhancer 2 (Pen-2), or synaptophysin (Syp) were altered in the absence of Syt1, suggesting a selective effect of Syt1 on PS1 and BACE1 trafficking. Conclusions Our findings identify Syt1 as a novel Ca2+-sensitive PS1 modulator that could regulate synaptic Aβ, opening avenues for novel and selective synapse targeting therapeutic strategies. Electronic supplementary material The online version of this article (doi:10.1186/s12915-016-0248-3) contains supplementary material, which is available to authorized users.

Accumulation of amyloid-β (Aβ) and neurofibrillary tangles in the brain, inflammation and synaptic and neuronal loss are some of the major neuropathological hallmarks of Alzheimer’s disease (AD). While genetic mutations in amyloid precursor protein and presenilin-1 and -2 (PS1 and PS2) genes cause early-onset familial AD, the etiology of sporadic AD is not fully understood. Our current study shows that changes in conformation of endogenous wild-type PS1, similar to those found with mutant PS1, occur in sporadic AD brain and during normal aging. Using a mouse model of Alzheimer’s disease (Tg2576) that overexpresses the Swedish mutation of amyloid precursor protein but has normal levels of endogenous wild-type presenilin, we report that the percentage of PS1 in a pathogenic conformation increases with age. Importantly, we found that this PS1 conformational shift is associated with amyloid pathology and precedes amyloid-β deposition in the brain. Furthermore, we found that oxidative stress, a common stress characteristic of aging and AD, causes pathogenic PS1 conformational change in neurons in vitro, which is accompanied by increased Aβ42/40 ratio. The results of this study provide important information about the timeline of pathogenic changes in PS1 conformation during aging and suggest that structural changes in PS1/γ-secretase may represent a molecular mechanism by which oxidative stress triggers amyloid-β accumulation in aging and in sporadic AD brain.

When queer students at Yeshiva University sued the school for discrimination in spring 2021, critics were quick to question why LGBTQ students would opt for an Orthodox Jewish university in the first place.But for many LGBTQ Orthodox Jews, as with believers of other faiths, their religious identities are as nonnegotiable as their queer identities. [ABSTRACT FROM PUBLISHER]

(RNS) ” When actor Daniel Franzese visited Jerusalem in November, he looked for God in all the usual places.But it wasn™t at the Western Wall or Mount of Olives where he encountered the divine, but in a hole-in-the-wall ™80s-style gay bar that was hosting a œDavid and Jonathan theme night for religious queer people. [ABSTRACT FROM PUBLISHER]

From left, University of St. Thomas students Helen Knudson, Arianna Norals, and Salma Nadir set up a table for decorating mason jars and headscarves at the school's celebration for the end of the Muslim holy month of Ramadan on the lawn in front of the Catholic chapel in St. Paul, Minn., on Saturday, May 7, 2022. Campus ministry helped organize the event, which included similar stress-reducing activities, as many faith leaders across US campuses seek ways to help students manage stress and anxiety. (AP Photo/Giovanna Dell'Orto) Sadaf Shier, standing, the Muslim chaplain at the University of St. Thomas, talks with students attending the school's celebration for the end of the Muslim holy month of Ramadan in St. Paul, Minn., on Saturday, May 7, 2022. She helped organize the event, which included several stress-reducing activities for students of any or no faith, as part of a broadening of the mission of campus ministry to address holistic student wellbeing. (AP Photo/Giovanna Dell'Orto) [ABSTRACT FROM PUBLISHER]