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The objective of this scoping review is to provide an overview of the available evidence on the effectiveness of web-based interventions for fear of cancer recurrence (FCR) and a discussion of drawbacks and possible improvements for web-based interventions identified in the reviewed studies. These steps fulfil the aim of this review, which is to offer suggestions for developing future web-based interventions based on the reviewed studies. Five databases (PubMed, MEDLINE, EMBASE, SCOPUS and Web of Science) were searched. Original peer-reviewed articles, written in English, on web-based interventions for FCR were included for review. The data from the included studies was synthesised thematically. We included 34 papers reporting on 28 interventions. Most of the studies in the papers were quantitative and mixed quantitative studies with a qualitative element, e.g. an interview post-intervention. Interventions were most commonly trialled with women breast cancer patients. Top three countries where studies were conducted were USA, Australia and the Netherlands. The most common theoretical framework for interventions is cognitive behavioural therapy (CBT), followed by mindfulness-based and mixed CBT, mindfulness, acceptance and commitment therapy (ACT), relaxation approaches. FCR was the primary focus/measure in 19 Studies, in 9 studies FCR was a secondary/related outcome/measure. Overall, the evidence of efficacy of web-based interventions on FCR is mixed. The existing research suggests several key points for producing more robust evidence about the effectiveness of web-based interventions for FCR. First, the studies suggest that it is a priority to better define eligibility criteria to proactively include people with higher levels of FCR. Second, there is a need for longer-term follow-up and outcome measuring period. Third, research examining the reasons for dropout from web-based interventions for FCR is critical to improve the effectiveness of web-based interventions. Fourth, while web-based interventions do not involve the costs of transportation, traveling time, space, equipment, cleaning, and other expenses, further cost utility analyses should be performed. Finally, future studies should assess how intervention accessibility, adherence, and effectiveness can be improved across different intervention designs, varying from intensive synchronous individual therapist-assisted web-based programme to blended designs combining the advantages of face-to-face and internet-based elements, to entirely self-managed programmes. Developing and evaluating more accessible FCR treatments have been identified among top international FCR research priorities (Shaw et al. 2021). While there is some evidence that web-based interventions can be as effective as face-to-face interventions, currently there is a dearth of systematic data about the ways in which the web-based modality specifically can enhance supportive care for FCR. Developing knowledge about effective web-based interventions has implications for cancer survivors as they can be presented with more accessible, low-cost and low-burden options for managing fear of cancer recurrence.

Although similar phenotypically, there is evidence that male and female breast cancer differ in their molecular landscapes. In this systematic review, we consolidated all existing prognostic biomarker data in male breast cancer spanning genetics, transcriptomics, proteomics, and epigenetics, and phenotypic features of prognostic value from articles published over a 29-year period (March 16, 1992, to May 1, 2021). We identified knowledge gaps in the existing literature, discussed limitations of the included studies, and outlined potential approaches for translational biomarker discovery and validation in male breast cancer. We also recognised STC2, DDX3, and DACH1 as underexploited markers of male-specific prognostic value in breast cancer. Finally, beyond describing the cumulative knowledge on the extensively researched markers oestrogen receptor-α, progesterone receptor, HER2, androgen receptor, and BRCA2, we highlighted ATM, CCND1, FGFR2, GATA3, HIF1-α, MDM2, TP53, and c-Myc as well studied predictors of poor survival that also aligned with several hallmarks of cancer.

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). 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. 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. 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.

IntroductionMammographic screening identifies many women with small breast cancers with favourable biological features, which have an excellent prognosis. Some of these may never have become clinically apparent without screening and are commonly described as ‘overdiagnosed’ cancers. Despite this, all patients with screen-detected cancers are currently treated with surgical excision and sentinel lymph node biopsy, although this may represent overtreatment. There is, therefore, a need for less invasive approaches to reduce treatment burden for patients while maintaining current excellent oncological outcomes. Vacuum-assisted excision (VAE) may represent such an alternative treatment approach, and the SMALL (Open Surgery versus Minimally invasive-vacuum Assisted excision for smaLL screen-detected breast cancer) trial aims to investigate the use of VAE for the safe de-escalation of surgical treatment for such excellent prognosis invasive breast cancers.MethodsSMALL is a prospective, multicentre, randomised phase III trial of VAE versus surgery in patients with small, biologically favourable screen-detected invasive breast cancer. SMALL has an innovative hybrid design with coprimary endpoints. These include a randomised non-inferiority comparison of surgical re-excision rates following initial treatment, and a single-arm analysis of local recurrence at 5 years following VAE. Secondary outcomes include complication rates, overall survival, quality of life and a health economic analysis. The trial includes a QuinteT Recruitment Intervention to support recruitment.Ethics and disseminationEthical approval was obtained from the Office for Research Ethics (Northern Ireland) for all UK sites. Results will be submitted for publication in a peer-reviewed journal, presented, shared with patient partners and with relevant professional organisations to inform future guideline development for the management of screen-detected breast cancer.Trial registration numberISRCTN12240119.

PurposeThe objective of this scoping review is to provide an overview of the available evidence on the effectiveness of web-based interventions for fear of cancer recurrence (FCR) and a discussion of drawbacks and possible improvements for web-based interventions identified in the reviewed studies. These steps fulfil the aim of this review, which is to offer suggestions for developing future web-based interventions based on the reviewed studies.MethodsFive databases (PubMed, MEDLINE, EMBASE, SCOPUS and Web of Science) were searched. Original peer-reviewed articles, written in English, on web-based interventions for FCR were included for review. The data from the included studies was synthesised thematically.ResultsWe included 34 papers reporting on 28 interventions. Most of the studies in the papers were quantitative and mixed quantitative studies with a qualitative element, e.g. an interview post-intervention. Interventions were most commonly trialled with women breast cancer patients. Top three countries where studies were conducted were USA, Australia and the Netherlands. The most common theoretical framework for interventions is cognitive behavioural therapy (CBT), followed by mindfulness-based and mixed CBT, mindfulness, acceptance and commitment therapy (ACT), relaxation approaches. FCR was the primary focus/measure in 19 Studies, in 9 studies FCR was a secondary/related outcome/measure. Overall, the evidence of efficacy of web-based interventions on FCR is mixed.ConclusionsThe existing research suggests several key points for producing more robust evidence about the effectiveness of web-based interventions for FCR. First, the studies suggest that it is a priority to better define eligibility criteria to proactively include people with higher levels of FCR. Second, there is a need for longer-term follow-up and outcome measuring period. Third, research examining the reasons for dropout from web-based interventions for FCR is critical to improve the effectiveness of web-based interventions. Fourth, while web-based interventions do not involve the costs of transportation, traveling time, space, equipment, cleaning, and other expenses, further cost utility analyses should be performed. Finally, future studies should assess how intervention accessibility, adherence, and effectiveness can be improved across different intervention designs, varying from intensive synchronous individual therapist-assisted web-based programme to blended designs combining the advantages of face-to-face and internet-based elements, to entirely self-managed programmes.Implications for cancer survivorsDeveloping and evaluating more accessible FCR treatments have been identified among top international FCR research priorities (Shaw et al. 2021). While there is some evidence that web-based interventions can be as effective as face-to-face interventions, currently there is a dearth of systematic data about the ways in which the web-based modality specifically can enhance supportive care for FCR. Developing knowledge about effective web-based interventions has implications for cancer survivors as they can be presented with more accessible, low-cost and low-burden options for managing fear of cancer recurrence.

Background/IntroductionAnthracycline-related cardiac dysfunction is a recognised consequence of cancer therapies. Here we assess resting cardiac and skeletal muscle energic status as an early mechanistic pathway of myocyte derangement and explore molecular targets of skeletal myocyte metabolism, protein synthesis/degradation and mitochondrial biogenesis signalling.MethodsWe conducted a prospective, mechanistic, observational, longitudinal study of chemotherapy-naive breast cancer patients undergoing anthracycline-based chemotherapy, compared to a healthy control group. 31P-Magnetic Resonance spectroscopy in cardiac and skeletal muscle (phosphocreatine/gamma adenosine triphosphate (PCr/yATP) and inorganic phosphate/phosphocreatine (Pi/PCr) ratios respectively), cardiac magnetic resonance (CMR) imaging inclusive of T1 and T2 mapping, echocardiography-derived global longitudinal strain function, serum NT-pro-BNP and skeletal muscle biopsies from the right vastus lateralis were assessed before and after 3 cycles of Flurouracil, Epirubicin and Cyclophosphamide followed by 3 cycles of Docetaxel. Statistical significance was set at p<0.05.ResultsTwenty-five female breast cancer patients (median age 53 years, range 32 – 74 years) receiving a mean epirubicin dose 307 mg/m2) and twenty-eight controls (median age 44 years, range 23 - 65) were recruited. All study assessments in breast cancer patients at pre-chemotherapy stage were comparable to the matched healthy controls. However, following chemotherapy, breast cancer patients demonstrated a small but significant reduction in cardiac function (global longitudinal strain -22.9 ± 3.9 vs -19.1 ± 3.3 %, p=0.01 and CMR-derived ejection fraction 65 ± 5 vs 62 ± 4 %, p=0.047), a mild increase in CMR-derived indexed left ventricular volumes (end diastolic 65 ± 10 vs 74 ± 11 ml/m2, p=0.014 and end systolic 23 ± 5 vs 28 ± 5 ml/m2, p=0.01) as well as an increase in left ventricular T1 and T2-mapping (1289 ± 29 vs 1321 ± 31 ms, p=0.004 and 50 ± 4 vs 55 ± 7 ms, p=0.027, respectively) and serum NT-Pro-BNP (49 ± 25 vs 108 ± 84 pg/m, p=0.008). After epirubicin, there was significant reduction in cardiac PCr/yATP ratio (2.0 ± 0.7 vs 1.2 ± 0.6, p=0.007) and a significant increase in skeletal muscle Pi/PCr ratio (0.13 ± 0.04 vs 0.22 ± 0.2, p=0.008) – Figure 1. Following chemotherapy, there was significant upregulation of skeletal myocyte protein synthesis (mammalian target of rapamycin, 0.44 ± 0.4 vs 0.53 ± 0.2, p<0.001) and degradation (Calcium/calmodulin dependent protein kinase II, 1.4 ± 0.7 vs 2.7 ± 1.1, p<0.001), metabolism (peroxisome proliferator-activated receptor gamma, 0.35 ± 0.2 vs 0.60 ± 0.1, p<0.001) and muscle mass regulator myostatin-2 (0.16 ± 0.1 vs 0.24 ± 0.1, p<0.001).Abstract 142 Figure 131P-MRS cardiac and skeletal muscle energetics. Data shown as median, 25th, and 75th percentile and maximum and minimum (whiskers). A - corrected PCr/γATP and B - Pi/PCr for controls and patients before chemotherapy and after chemotherapy. Example spectra showing: phosphocreatine (PCr), γ, β, and α adenosine triphosphate (ATP), and 2,3-diphosphoglycerate (2,3 DPG) peaks before (C) and after (D) chemotherapy; (Pi), phosphocreatine (PCr) and γ, β, and α adenosine triphosphate (ATP) peaks before (E) and after (F) chemotherapyConclusionContemporary doses of epirubicin for breast cancer result in significant reduction of cardiac and skeletal muscle high energy 31P-metabolism alongside skeletal myocellular alterations of protein synthesis and metabolic regulation pathways.Conflict of InterestNone

Male breast cancer (MBC) is a rare disease that accounts for less than 1% of all breast cancers and male malignancies. Despite recognised clinico-pathological and molecular differences to female breast cancer (FBC), the clinical management of MBC follows established FBC treatment strategies. Loss of function mutations in the DNA damage response genes BRCA1 and BRCA2, have been strongly implicated in the pathogenesis of MBC. While there have been extensive clinical advancements in other BRCA-related malignancies, including FBC, improvements in MBC remain stagnant. Here we present a review that highlights the lack of treatment evidence for BRCA-related MBC and the required national and global collaborative effort to address this unmet need. In doing so, we summarise the transformative clinical advancements with poly(ADP-ribose) polymerase (PARP) inhibitors in other BRCA-related cancers namely, FBC and prostate cancer.

PurposeThe B-MaP-C study investigated changes to breast cancer care that were necessitated by the COVID-19 pandemic. Here we present a follow-up analysis of those patients commenced on bridging endocrine therapy (BrET), whilst they were awaiting surgery due to reprioritisation of resources.MethodsThis multicentre, multinational cohort study recruited 6045 patients from the UK, Spain and Portugal during the peak pandemic period (Feb–July 2020). Patients on BrET were followed up to investigate the duration of, and response to, BrET. This included changes in tumour size to reflect downstaging potential, and changes in cellular proliferation (Ki67), as a marker of prognosis.Results1094 patients were prescribed BrET, over a median period of 53 days (IQR 32–81 days). The majority of patients (95.6%) had strong ER expression (Allred score 7–8/8). Very few patients required expedited surgery, due to lack of response (1.2%) or due to lack of tolerance/compliance (0.8%). There were small reductions in median tumour size after 3 months’ treatment duration; median of 4 mm [IQR − 20, 4]. In a small subset of patients (n = 47), a drop in cellular proliferation (Ki67) occurred in 26 patients (55%), from high (Ki67 ≥ 10%) to low (< 10%), with at least one month’s duration of BrET.DiscussionThis study describes real-world usage of pre-operative endocrine therapy as necessitated by the pandemic. BrET was found to be tolerable and safe. The data support short-term (≤ 3 months) usage of pre-operative endocrine therapy. Longer-term use should be investigated in future trials.

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.

C-reactive protein (CRP) is an acute phase protein implicated in the progression of cancer. A positive correlation between tumour stage and plasma CRP levels was demonstrated in prostate cancer, indicating a relationship between raised CRP levels and more aggressive disease, suggesting a role for inflammatory response in tumour progression. Aim of this study was to assess the tumoural presence and cellular location of CRP and establish if these are linked to clincopathological features of the cohort and patient survival. Tissue microarray technology was employed to analyse 50 matched pairs of hormone sensitive and refractory prostate cancers. Immunohistochemistry was performed using antibody to CRP. CRP was assessed using the weighted histoscore method. CRP presence was observed in the cytoplasm and nucleus of selected tumours. Cytoplasmic CRP correlated positively with metastases at diagnosis ( P =0.039), whereas nuclear CRP presence correlated with metastases at relapse ( P =0.006). A trend towards an increase in cytoplasmic and nuclear CRP presence from hormone sensitive to hormone refractory tumours was noticed. No significant association between tumoural CRP presence, time to biochemical relapse or disease-specific survival was observed. Tumoural CRP is likely to have a role in progression of prostate cancer, as it is associated with increased presence of metastases at the time of diagnosis and time of relapse. A larger powered study is necessary to establish if CRP presence is associated with disease-specific survival.