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Predictors of Disruptions in Breast Cancer Care for Individuals with Schizophrenia.

ABSTRACT: BACKGROUND:Patients with schizophrenia experience markedly increased breast cancer mortality, yet reasons for this disparity are poorly understood. We sought to characterize disruptions in breast cancer care for patients with schizophrenia and identify modifiable predictors of those disruptions. MATERIALS AND METHODS:We performed a medical record review of 95 patients with schizophrenia and breast cancer treated at an academic cancer center between 1993 and 2015. We defined cancer care disruptions as processes that interfere with guideline-concordant cancer care, including delays to diagnosis or treatment, deviations from stage-appropriate treatment, and interruptions in treatment. We hypothesized that lack of psychiatric treatment at cancer diagnosis would be associated with care disruptions. RESULTS:Half of patients with schizophrenia experienced at least one breast cancer care disruption. Deviations in stage-appropriate treatment were associated with breast cancer recurrence at 5 years (p?=?.045). Patients without a documented psychiatrist experienced more delays (p?=?.016), without documented antipsychotic medication experienced more deviations (p?=?.007), and with psychiatric hospitalizations after cancer diagnosis experienced more interruptions (p?

SUBMITTER: Irwin KE

PROVIDER: S-EPMC5679818 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Predictors of Disruptions in Breast Cancer Care for Individuals with Schizophrenia.

Irwin Kelly E KE Park Elyse R ER Shin Jennifer A JA Fields Lauren E LE Jacobs Jamie M JM Greer Joseph A JA Taylor John B JB Taghian Alphonse G AG Freudenreich Oliver O Ryan David P DP Pirl William F WF

The oncologist 20170530 11

<h4>Background</h4>Patients with schizophrenia experience markedly increased breast cancer mortality, yet reasons for this disparity are poorly understood. We sought to characterize disruptions in breast cancer care for patients with schizophrenia and identify modifiable predictors of those disruptions.<h4>Materials and methods</h4>We performed a medical record review of 95 patients with schizophrenia and breast cancer treated at an academic cancer center between 1993 and 2015. We defined cancer ...[more]

PMID: 28559411

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Project description:PURPOSE:The Predictors of Breast Cancer Recurrence (ProBe CaRe) study was established to evaluate modification of tamoxifen (TAM) effectiveness in premenopausal women through reduced activity of TAM-metabolising enzymes. It comprehensively evaluates the effects of pharmacogenetic variants, use of concomitant medications and biomarkers involved in oestrogen metabolism on breast cancer recurrence risk. PARTICIPANTS:The ProBe CaRe study was established using resources from the Danish Breast Cancer Group (DBCG), including 5959 premenopausal women diagnosed with stage I-III primary breast cancer between 2002 and 2010 in Denmark. Eligible participants were divided into two groups based on oestrogen receptor alpha (ER?) expression and receipt of TAM therapy, 4600 are classified as ER?+/TAM+ and 1359 are classified as ER?-/TAM-. The ProBe CaRe study is a population-based cohort study nested in a nearly complete source population, clinical, tumour and demographic data were abstracted from DBCG registry data. Linkage to Danish registries allows for abstraction of information regarding comorbid conditions, comedication use and mortality. Formalin-fixed paraffin-embedded tissue samples have been prepared for DNA extraction and immunohistochemical assay. FINDINGS TO DATE:To mitigate incorrect classification of patients into specific categories, we conducted a validation substudy. We compared data acquired from registry and from medical record review to calculate positive predictive values (PPVs) and negative predictive values. We observed PPVs near 100% for tumour size, lymph node involvement, receptor status, surgery type, receipt of radiotherapy, receipt of chemotherapy and TAM treatment. We found that the PPVs were 96% (95% CI 83% to 100%) for change in endocrine therapy and 61% (95% CI 42% to 77%) for menopausal transition. FUTURE PLANS:The ProBeCaRe cohort study is well positioned to comprehensively examine pharmacogenetic variants. We will use a Bayesian pathway analysis to evaluate the complete TAM metabolic path to allow for gene-gene interactions, incorporating information of other important patient characteristics.

Project description:ObjectiveTo investigate how primary care access, intensity and quality of care changed among patients living with schizophrenia before and after the onset of the COVID-19 pandemic in Ontario, Canada.MethodsThis cohort study was performed using primary care electronic medical record data from the University of Toronto Practice-Based Research Network (UTOPIAN), a network of > 500 family physicians in Ontario, Canada. Data were collected during primary care visits from 2643 patients living with schizophrenia. Rates of primary care health service use (in-person and virtual visits with family physicians) and key preventive health indices indicated in antipsychotic monitoring (blood pressure readings, hemoglobin A1c, cholesterol and complete blood cell count [CBC] tests) were measured and compared in the 12 months before and after onset of the COVID-19 pandemic.ResultsAccess to in-person care dropped with the onset of the COVID-19 pandemic. During the first year of the pandemic only 39.5% of patients with schizophrenia had at least one in-person visit compared to 81.0% the year prior. There was a corresponding increase in virtual visits such that 78.0% of patients had a primary care appointment virtually during the pandemic period. Patients prescribed injectable antipsychotics were more likely to continue having more frequent in-person appointments during the pandemic than patients prescribed only oral or no antipsychotic medications. The proportion of patients who did not have recommended tests increased from 41.0% to 72.4% for blood pressure readings, from 48.9% to 60.2% for hemoglobin A1c, from 57.0% to 67.8% for LDL cholesterol and 45.0% to 56.0% for CBC tests during the pandemic.ConclusionsThere were substantial decreases in preventive care after the onset of the pandemic, although primary care access was largely maintained through virtual care. Addressing these deficiencies will be essential to promoting health equity and reducing the risk of poor health outcomes.

Project description:Background: Numerous studies have focused on the PI3K/AKT/mTOR pathway in estrogen receptor positive (ER) breast cancer (BC), as a linear signal transduction pathway and reported its association with worse clinical outcomes. To gain better insight into the relative contribution of each of the signalling pathways which lie downstream to PI3K (namely AKT and mTOR) to BC outcomes, we have developed a novel in silico approach which assessed the activation of each of these signalling pathways separately. Methods: By analysing gene expression and matched proteomic data in ER-positive patients from the TCGA repository, we developed gene signatures that reflect the level of expression of phosphorylated-Serine473-AKT (pAKT) and phosphorylated-Serine2448-mTOR (p-mTOR) separately, capturing their corresponding level of pathway activation. Using pooled analysis of gene-expression data from over 7,000 patients with ER-positive early BC, we then investigated the association between pathway activation and outcomes. Results: Our analysis revealed that the pAKT pathway activation (as measured by the developed signature) was associated with luminal A BC while the p-mTOR pathway activation was more associated with luminal B BC (Kruskal-Wallis test p<10-10). pAKT pathway activation was significantly associated with better outcomes (multivariable HR, 0.79; 95% CI, 0.74 to 0.85; p=2.5x10-10) whereas p-mTOR pathway activation showed worse outcomes (multivariable HR, 1.1; 95% CI, 1.1 to 1.2; p=9.9x10-4). Similar associations between activation and outcomes were obtained when the analysis was performed in patients who were treated with hormonal therapy. Additionally, pAKT pathway activation predicted better outcomes irrespective of the BC molecular subtypes (luminal A multivariable HR, 0.85; 95% CI, 0.75 to 0.96; p=0.01; luminal B HR, 0.91; 95% CI, 0.83 to 0.99; p=0.033). pAKT pathway activation was associated with PIK3CA mutations (p=0.0001) while p-mTOR pathway activation was associated with p53 mutations (p=0.04). Finally, we show that pAKT pathway activation was associated with less response to Everolimus. Conclusions: Our data show that pAKT and p-mTOR pathway activation have differing impact on prognosis and suggest that they are not linearly connected in luminal breast cancers. These findings add to our understanding of signalling through the PI3K pathway and could have important implications for the treatment of luminal BC.

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Predictors of Disruptions in Breast Cancer Care for Individuals with Schizophrenia.

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Predictors of Disruptions in Breast Cancer Care for Individuals with Schizophrenia.

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