ORCID Profile
0000-0002-2705-7459
Current Organisation
Peter MacCallum Cancer Centre
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Publisher: JMIR Publications Inc.
Date: 23-04-2023
DOI: 10.2196/48432
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22478397.V1
Abstract: Supplementary Material
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6529944
Abstract: AbstractPurpose: The majority of deaths from breast cancer occur following the development of metastatic disease, a process inhibited by β-blockers in preclinical studies. This phase II randomized controlled trial evaluated the effect of preoperative β-blockade with propranolol on biomarkers of metastatic potential and the immune cell profile within the primary tumor of patients with breast cancer. Patients and Methods: In this triple-blind placebo-controlled clinical trial, 60 patients were randomly assigned to receive an escalating dose of oral propranolol ( i n /i = 30 80–160 mg daily) or placebo ( i n /i = 30) for 7 days prior to surgery. The primary endpoint investigated the effect of propranolol on prometastatic and proinflammatory gene expression within the primary tumor. Results: Propranolol downregulated primary tumor expression of mesenchymal genes ( i P /i = 0.002) without affecting epithelial gene expression ( i P /i = 0.21). Bioinformatic analyses implicated downregulation of Snail/Slug ( i P /i = 0.03), NF-κB/Rel ( i P /i 0.01), and AP-1 ( i P /i 0.01) transcription factors in structuring the observed transcriptome alterations, and identified changes in intratumoral neutrophil, natural killer cell, and dendritic cell recruitment (all i P /i 0.01). Patients with clinical evidence of drug response (lowered heart rate and blood pressure) demonstrated elevated tumor infiltration of CD68 sup + /sup macrophages and CD8 sup + /sup T cells. Conclusions: One week of β-blockade with propranolol reduced intratumoral mesenchymal polarization and promoted immune cell infiltration in early-stage surgically-resectable breast cancer. These results show that β-blockade reduces biomarkers associated with metastatic potential, and support the need for larger phase III clinical trials powered to detect the impact of β-blockade on cancer recurrence and survival. i See related commentary by Blaes et al., p. 1781 /i /
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22478397
Abstract: Supplementary Material
Publisher: American Association for Cancer Research (AACR)
Date: 15-04-2020
DOI: 10.1158/1078-0432.CCR-19-2641
Abstract: The majority of deaths from breast cancer occur following the development of metastatic disease, a process inhibited by β-blockers in preclinical studies. This phase II randomized controlled trial evaluated the effect of preoperative β-blockade with propranolol on biomarkers of metastatic potential and the immune cell profile within the primary tumor of patients with breast cancer. In this triple-blind placebo-controlled clinical trial, 60 patients were randomly assigned to receive an escalating dose of oral propranolol (n = 30 80–160 mg daily) or placebo (n = 30) for 7 days prior to surgery. The primary endpoint investigated the effect of propranolol on prometastatic and proinflammatory gene expression within the primary tumor. Propranolol downregulated primary tumor expression of mesenchymal genes (P = 0.002) without affecting epithelial gene expression (P = 0.21). Bioinformatic analyses implicated downregulation of Snail/Slug (P = 0.03), NF-κB/Rel (P & 0.01), and AP-1 (P & 0.01) transcription factors in structuring the observed transcriptome alterations, and identified changes in intratumoral neutrophil, natural killer cell, and dendritic cell recruitment (all P & 0.01). Patients with clinical evidence of drug response (lowered heart rate and blood pressure) demonstrated elevated tumor infiltration of CD68+ macrophages and CD8+ T cells. One week of β-blockade with propranolol reduced intratumoral mesenchymal polarization and promoted immune cell infiltration in early-stage surgically-resectable breast cancer. These results show that β-blockade reduces biomarkers associated with metastatic potential, and support the need for larger phase III clinical trials powered to detect the impact of β-blockade on cancer recurrence and survival. See related commentary by Blaes et al., p. 1781
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6529944.V1
Abstract: AbstractPurpose: The majority of deaths from breast cancer occur following the development of metastatic disease, a process inhibited by β-blockers in preclinical studies. This phase II randomized controlled trial evaluated the effect of preoperative β-blockade with propranolol on biomarkers of metastatic potential and the immune cell profile within the primary tumor of patients with breast cancer. Patients and Methods: In this triple-blind placebo-controlled clinical trial, 60 patients were randomly assigned to receive an escalating dose of oral propranolol ( i n /i = 30 80–160 mg daily) or placebo ( i n /i = 30) for 7 days prior to surgery. The primary endpoint investigated the effect of propranolol on prometastatic and proinflammatory gene expression within the primary tumor. Results: Propranolol downregulated primary tumor expression of mesenchymal genes ( i P /i = 0.002) without affecting epithelial gene expression ( i P /i = 0.21). Bioinformatic analyses implicated downregulation of Snail/Slug ( i P /i = 0.03), NF-κB/Rel ( i P /i 0.01), and AP-1 ( i P /i 0.01) transcription factors in structuring the observed transcriptome alterations, and identified changes in intratumoral neutrophil, natural killer cell, and dendritic cell recruitment (all i P /i 0.01). Patients with clinical evidence of drug response (lowered heart rate and blood pressure) demonstrated elevated tumor infiltration of CD68 sup + /sup macrophages and CD8 sup + /sup T cells. Conclusions: One week of β-blockade with propranolol reduced intratumoral mesenchymal polarization and promoted immune cell infiltration in early-stage surgically-resectable breast cancer. These results show that β-blockade reduces biomarkers associated with metastatic potential, and support the need for larger phase III clinical trials powered to detect the impact of β-blockade on cancer recurrence and survival. i See related commentary by Blaes et al., p. 1781 /i /
Publisher: JMIR Publications Inc.
Date: 23-04-2023
Abstract: he past decade saw remarkable advances in cancer care, treatment and outcomes, but the benefits were not experienced equally by all. Disparities are largely driven by social determinants of health and associated structural barriers. Specialist cancer nurses can ameliorate inequity of opportunity for optimal care, treatment and outcomes through timely screening, assessment and intervention. We designed a nursing complexity checklist (the Checklist) to support these activities, with the ultimate goal of reducing disparities in opportunity of access for people diagnosed with cancer. The aim of this study is to understand the clinical utility of the Checklist including issues affecting adoption into routine practice. rimary objectives are to assess the appropriateness, acceptability, and practicability of the Checklist from the perspective of cancer patients and specialist nurses core aspects of each dimension were selected from Smart’s multi-dimensional model of clinical utility. Secondary objectives focus on two aspects of the practicability dimension including a preliminary investigation of the predictive value of the Checklist and concordance between specific checklist items and patient-reported outcome measures (PROMs). p to sixty newly diagnosed cancer patients and ten specialist nurses will be recruited from a specialist cancer centre into this prospective mixed-methods case series study. The Checklist will be completed by a specialist nurse with patient participants. Within two weeks of Checklist completion, patients will complete five PROMs with established psychometric properties that correspond to specific checklist items and an in idual semi-structured interview to explore its acceptability. Interviews with specialist nurses will occur 12 and 24 weeks after they first complete a checklist to explore multiple aspects of clinical utility including barriers and facilitators to effective implementation. Data regarding planned and unplanned patient service-use will be collected from patient follow-up interviews at 12 weeks and the electronic medical record (EMR) at 24 weeks after Checklist completion. Descriptive statistics will be used to summarise operational, checklist and EMR data. Contingency tables and conditional probabilities will be used to explore the predictive value of the Checklist. Descriptive statistics, Cohen’s d/U3 and plots will be used to explore the relationship between specific checklist items and relevant PROMs. Qualitative data will be analysed using a content analysis approach. his study was approved by the institution’s ethics committee. The enrolment period commenced May 2022 and ended November 2022. Thirty-seven cancer patients and seven specialist cancer nurses were recruited in this time. Data collection is scheduled for completion at the end of May 2023. his prospective mixed-methods case series study will evaluate the clinical utility of a nursing complexity checklist. It will also provide preliminary evidence on its predictive value and information to support its seamless implementation into everyday practice including, but not limited to, possible revisions to the Checklist, instructions and training for relevant personnel.
No related grants have been discovered for Elizabeth Crone.