The role of Src kinase and Src kinase family members in breast cancer

This project highlighted that Src and Src kinase family (SFK) members play a definitive role in breast cancer. Due to the paucity of translational studies, we investigated if SFK members are expressed in human breast tissue. Eight SFK members were present with distinct mRNA expression patterns in normal, non-malignant and malignant breast tissue. Immunohistochemistry was employed to investigate protein expression and activation of Src and SFK members. Survival analysis revealed that c-Src and activated Y419Src were associated with worse patient outcome, confirming current in vitro literature, whereas a different phosphorylation site of Src (Y215) and expression of Lck was associated with improved clinical outcome. Dasatinib was employed in different breast cancer cell lines to establish its effect on those phosphorylation sites. Decreased expression of c-Src and Y419Src was observed, whilst Y215Src expression stayed unchanged, providing a rationale for using this Src kinase inhibitor in clinical trials

Impalpable Breast Cancer and Service Delivery during the COVID-19 Pandemic : the Role of Radiofrequency Tag localization

Funding Information: The authors would like to thank Friends of Anchor for their generous grant that enabled the trial of RF tags in Aberdeen, and all the staff in the Unit at Aberdeen Royal Infirmary and BMI Albyn Hospital for making this possible.Peer reviewedPublisher PD

Insomnia prehabilitation in newly diagnosed breast cancer patients: Protocol for a pilot, multicentre, randomised controlled trial comparing nurse delivered sleep restriction therapy to sleep hygiene education (INVEST trial)

Introduction: Insomnia is a prevalent sleep disorder that negatively impacts daytime functioning and quality of life. Breast cancer patients report higher rates of insomnia and more circadian disruption than other cancer groups. Approximately 50% of patients experience acute insomnia following breast cancer diagnosis, which often persists during cancer treatment and rehabilitation. Sleep Restriction Therapy (SRT) is a clinically effective and tolerable treatment for persistent insomnia in breast cancer survivors. However, SRT has never been tested on patients with early signs of sleep disturbance who are undergoing cancer treatment. The aim of this pilot randomised controlled trial is to explore the feasibility and preliminary effectiveness of nurse delivered SRT for newly diagnosed breast cancer patients with acute insomnia. The trial has been registered on ClinicalTrials.gov (identifier: NCT06294041). Methods: The INVEST (INvestigating the Value of Early Sleep Therapy) trial will recruit 50 newly diagnosed breast cancer patients who meet criteria for acute insomnia. Patients will be recruited from breast cancer results clinics within two Scottish health boards (NHS Grampian and NHS Greater Glasgow and Clyde) and will be block randomised (1:1) to receive nurse delivered SRT or Sleep Hygiene Education (SHE). SRT will be delivered over 4 weekly sessions comprising two face-to-face meetings (either in person or online) and two telephone calls, whereas SHE will be administered in booklet form. Outcomes will be collected at baseline, 6 weeks, and 12 weeks post-randomisation. Primary outcomes in this trial relate to the feasibility of SRT for newly diagnosed breast cancer patients with acute insomnia. Specifically, we will explore (i) rates of patient recruitment and retention, (ii) intervention fidelity, (iii) data collection procedures and outcome measure completion, (iv) intervention acceptability. Secondary outcomes will focus on preliminary evaluation of patient responses to SRT, including insomnia severity, rest-activity rhythms, and mental health. Dissemination: Our dissemination plan comprises publishing trial outcomes in high-impact, peer-reviewed journals and on breast cancer charity websites and other patient resources. The outcomes from this pilot trial will also inform the development of a full-scale, multicentre RCT of SRT for acute insomnia in newly diagnosed breast cancer patients. University of Strathclyde is the sponsor (reference: UEC23/52). Protocol version v1.2 4 October 2023. Strengths and limitations of this study: This trial is the first to explore the value of sleep prehabilitation for newly diagnosed breast cancer patients. This will be the first trial to assess the feasibility of delivering SRT during breast cancer treatment, providing valuable insight into its tolerability and preliminary effectiveness. An embedded process evaluation will assess the acceptability of SRT, providing insight into potential optimisation of the intervention and recommendations for enhancing its future scalability and translation within cancer care. Due to the nature of the SRT intervention, nurse therapists and patients cannot be blinded to treatment allocation, increasing the risk of bias

Defining genomic, transcriptomic, proteomic, epigenetic, and phenotypic biomarkers with prognostic capability in male breast cancer : a systematic review

Peer reviewedPostprin

The Role of redo-Sentinel Lymph Node Biopsy in Patients With Prior Ipsilateral Breast Cancer Surgery

Acknowledgments There is no funding for this project as this is a retrospective review of our practice. This project did not get any grants or funding in the public, commercial or a none profit sector. Open Access via Elsevier agreement.Peer reviewedPublisher PD

Insomnia prehabilitation in newly diagnosed breast cancer patients : protocol for a pilot, multicentre, randomised controlled trial comparing nurse delivered sleep restriction therapy to sleep hygiene education (INVEST trial)

Introduction Insomnia is a prevalent sleep disorder that negatively impacts daytime functioning and quality of life. Breast cancer patients report higher rates of insomnia and more circadian disruption than other cancer groups. Approximately 50% of patients experience acute insomnia following breast cancer diagnosis, which often persists during cancer treatment and rehabilitation. Sleep Restriction Therapy (SRT) is a clinically effective and tolerable treatment for persistent insomnia in breast cancer survivors. However, SRT has never been tested on patients with early signs of sleep disturbance who are undergoing cancer treatment. The aim of this pilot randomised controlled trial is to explore the feasibility and preliminary effectiveness of nurse delivered SRT for newly diagnosed breast cancer patients with acute insomnia. The trial has been registered on ClinicalTrials.gov (identifier: NCT06294041). Methods The INVEST (INvestigating the Value of Early Sleep Therapy) trial will recruit 50 newly diagnosed breast cancer patients who meet criteria for acute insomnia. Patients will be recruited from breast cancer results clinics within two Scottish health boards (NHS Grampian and NHS Greater Glasgow and Clyde) and will be block randomised (1:1) to receive nurse delivered SRT or Sleep Hygiene Education (SHE). SRT will be delivered over 4 weekly sessions comprising two face-to-face meetings (either in person or online) and two telephone calls, whereas SHE will be administered in booklet form. Outcomes will be collected at baseline, 6 weeks, and 12 weeks post-randomisation. Primary outcomes in this trial relate to the feasibility of SRT for newly diagnosed breast cancer patients with acute insomnia. Specifically, we will explore (i) rates of patient recruitment and retention, (ii) intervention fidelity, (iii) data collection procedures and outcome measure completion, (iv) intervention acceptability. Secondary outcomes will focus on preliminary evaluation of patient responses to SRT, including insomnia severity, rest-activity rhythms, and mental health. Dissemination Our dissemination plan comprises publishing trial outcomes in high-impact, peer-reviewed journals and on breast cancer charity websites and other patient resources. The outcomes from this pilot trial will also inform the development of a full-scale, multicentre RCT of SRT for acute insomnia in newly diagnosed breast cancer patients. University of Strathclyde is the sponsor (reference: UEC23/52). Protocol version v1.2 4 October 2023

Impaired Cardiac and Skeletal Muscle Energetics Following Anthracycline Therapy for Breast Cancer

Acknowledgments The fellow (Dr Gamble) recruited participants, scheduled, coordinated, and performed all clinical imaging investigations, patients skeletal muscle biopsies and venesection, conducted mitochondrial copy number analysis of muscle biopsies under supervision, analyzed all data, performed statistical analyses under supervision, and drafted this article. H. Khan and A. Rudd helped with the investigations and reviewed and contributed to this article. S. Baliga provided the healthy volunteer skeletal muscle biopsies. Dr Ross designed and developed the protocol for cardiac and skeletal muscle spectroscopy. L. Cheyne supervised muscle biopsy analyses. Drs Unger and Linke performed the skeletal muscle transmission electron microscopy and immunofluorescence confocal microscopy investigations. Dr Horgan is the study statistician. Drs Urquhart, Masannat, Elsberger, Fuller, Mustafa, and Sharma identified and recruited participants and reviewed and contributed to this article. Drs Hannah, Sharma, and Saunders contributed to the design of the study. D. Dawson (PI) designed the study, obtained funding (together with Drs Sharma and Masannat) and regulatory approvals, supervised the unfolding of the study, its analyses and revised the article drafts. Sources of Funding Tenovus Scotland G18.01, D. Dawson and Dr Sharma, Friends of Anchor 2019, Grampian National Health Service-Endowments (Drs Sharma and Masannat), British Health Foundation PG/18/35/33786 to D. Dawson funded DG salary and BHF FS/RTF/20/30009 to D. Dawson funded AR salary.Peer reviewedPublisher PD

The NeST (Neoadjuvant systemic therapy in breast cancer) study: National Practice Questionnaire of United Kingdom multi-disciplinary decision making

Abstract: Background: Neoadjuvant systemic therapy (NST) is increasingly used in the treatment of breast cancer, yet it is clear that there is significant geographical variation in its use in the UK. This study aimed to examine stated practice across UK breast units, in terms of indications for use, radiological monitoring, pathological reporting of treatment response, and post-treatment surgical management. Methods: Multidisciplinary teams (MDTs) from all UK breast units were invited to participate in the NeST study. A detailed questionnaire assessing current stated practice was distributed to all participating units in December 2017 and data collated securely usingREDCap. Descriptive statistics were calculated for each questionnaire item. Results: Thirty-nine MDTs from a diverse range of hospitals responded. All MDTs routinely offered neoadjuvant chemotherapy (NACT) to a median of 10% (range 5–60%) of patients. Neoadjuvant endocrine therapy (NET) was offered to a median of 4% (range 0–25%) of patients by 66% of MDTs. The principal indication given for use of neoadjuvant therapy was for surgical downstaging. There was no consensus on methods of radiological monitoring of response, and a wide variety of pathological reporting systems were used to assess tumour response. Twenty-five percent of centres reported resecting the original tumour footprint, irrespective of clinical/radiological response. Radiologically negative axillae at diagnosis routinely had post-NACT or post-NET sentinel lymph node biopsy (SLNB) in 73.0 and 84% of centres respectively, whereas 16% performed SLNB pre-NACT. Positive axillae at diagnosis would receive axillary node clearance at 60% of centres, regardless of response to NACT. Discussion: There is wide variation in the stated use of neoadjuvant systemic therapy across the UK, with general low usage of NET. Surgical downstaging remains the most common indication of the use of NAC, although not all centres leverage the benefits of NAC for de-escalating surgery to the breast and/or axilla. There is a need for agreed multidisciplinary guidance for optimising selection and management of patients for NST. These findings will be corroborated in phase II of the NeST study which is a national collaborative prospective audit of NST utilisation and clinical outcomes

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown