Publications by authors named "Stuart McIntosh"

Introduction: The use of primary systemic therapy (PST) in early invasive breast cancer is routine but there are concerns about risk of locoregional recurrence.

Methods: We conducted a systematic literature review to identify studies of locoregional treatment and recurrence in patients with early invasive breast cancer who received non-endocrine PST.

Results: We identified 112 studies (18 prospective trials and 94 non-interventional studies).

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Background: Surgical de-escalation aims to reduce morbidity without compromising oncological outcomes. Trials to de-escalate breast cancer (BC) surgery among exceptional responders after neoadjuvant systemic therapy (NST) are ongoing. Combined patient and clinician insights on this strategy are unknown.

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Accurate information about locoregional treatments in breast cancer neoadjuvant systemic therapy (NST) trials is vital to support surgical decision-making and allow meaningful interpretation of long-term oncological outcomes. This systematic review (PROSPERO registration CRD42023470891) aimed to describe the current practice of outcome reporting in NST studies. A systematic search identified primary research studies published 01/01/2018-08/09/2023 reporting outcomes in patients receiving NST for breast cancer followed by locoregional treatment.

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Purpose: To use robust consensus methods with individuals with lived breast cancer experience to agree the top 10 research priorities to improve information and support for patients undergoing breast cancer surgery in the UK.

Methods: Research uncertainties related to information and support for breast cancer surgery submitted by patients and carers were analysed thematically to generate summary questions for inclusion in an online Delphi survey. Individuals with lived breast cancer experience completed two Delphi rounds including feedback in which they selected their top 10 research priorities from the list provided.

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Synopsis: This is a systematic review and meta-analysis comparing surgical excision with percutaneous ultrasound-guided vacuum-assisted excision (US-VAE) for the treatment of benign phyllodes tumor (PT) using local recurrence (LR) as the endpoint.

Objective: To determine the frequency of local recurrence (LR) of benign phyllodes tumor (PT) after ultrasound-guided vacuum-assisted excision (US-VAE) compared to the frequency of LR after surgical excision.

Method: A systematic review and meta-analysis [following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard] was conducted by comparing LR in women older than 18 years treated for benign PT by US-VAE compared with local surgical excision with at least 12 months of follow-up.

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Background: Breast cancer treatment is multimodal, but not all patients benefit from each treatment, and many experience morbidities significantly impacting quality of life. There is increasing interest in tailoring breast cancer treatments to optimize oncological outcomes and reduce treatment burden, but it is vital that future trials focus on treatments that most impact patients. This study was designed to explore patient experiences of treatment to inform future research.

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Introduction: Neoadjuvant systemic anticancer therapy (neoSACT) is increasingly used in the treatment of early breast cancer. Response to therapy is prognostic and allows locoregional and adjuvant systemic treatments to be tailored to minimise morbidity and optimise oncological outcomes and quality of life. Accurate information about locoregional treatments following neoSACT is vital to allow the translation of downstaging benefits into practice and facilitate meaningful interpretation of oncological outcomes, particularly locoregional recurrence.

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Background: Despite a UK 5-year breast cancer survival rate of 86.6%, patients may develop breast cancer recurrence within the same breast after breast conserving surgery, as well as in the remaining skin or chest wall after mastectomy or in the ipsilateral lymph glands. These recurrences, collectively termed locoregional recurrence (LRR), occur in around 8% of patients within 10 years of their original diagnosis.

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Breast cancer screening programmes frequently detect early, good prognosis breast cancers with significant treatment burden for patients, and associated health-cost implications. Emerging evidence suggests a role for minimally invasive techniques in the management of these patients enabling many women to avoid surgical intervention. Minimally invasive techniques include vacuum-assisted excision, cryoablation, and radiofrequency ablation.

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Background: Literature meta-analysis results show that digital breast tomosynthesis (DBT) combined with synthesized two-dimensional (s2D) mammograms can reduce recalls and improve breast cancer detection. Uncertainty regarding the screening of patients with breast cancer presents a health economic challenge, both in terms of healthcare resource use and quality of life impact on patients.

Objective: This study aims to estimate the cost effectiveness of DBT + s2D versus digital mammography (DM) used in a biennial breast cancer screening setting of women aged 40-69 years with scattered areas of fibroglandular breast density and heterogeneous dense breasts in the Brazilian supplementary health system.

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Aims: To conduct a definitive multicentre comparison of digital pathology (DP) with light microscopy (LM) for reporting histopathology slides including breast and bowel cancer screening samples.

Methods: A total of 2024 cases (608 breast, 607 GI, 609 skin, 200 renal) were studied, including 207 breast and 250 bowel cancer screening samples. Cases were examined by four pathologists (16 study pathologists across the four speciality groups), using both LM and DP, with the order randomly assigned and 6 weeks between viewings.

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Objective: An estimated one-third of cancer patients experience a clinically significant psychological disorder, however it is unclear to what extent this is reflected in research funding. To address this a systematic analysis the allocation of psycho-oncology research funding globally between 2016 and 2020 was conducted.

Methods: A global dataset of 66,388 cancer research awards, from 2016 to 2020 inclusive and totalling $24.

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Background: The aim of this multicentre prospective audit was to describe the current practice in the management of mastitis and breast abscesses in the UK and Ireland, with a specific focus on rates of surgical intervention.

Methods: This audit was conducted in two phases from August 2020 to August 2021; a phase 1 practice survey and a phase 2 prospective audit. Primary outcome measurements for phase 2 included patient management pathway characteristics and treatment type (medical/radiological/surgical).

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Importance: Genitourinary syndrome of menopause can be treated with vaginal estrogen therapy. However, there are concerns about the safety of vaginal estrogen therapy in patients with breast cancer.

Objective: To determine whether the risk of breast cancer-specific mortality was higher in females with breast cancer who used vaginal estrogen therapy vs females with breast cancer who did not use hormone replacement therapy (HRT).

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Samuraciclib is a selective oral CDK7-inhibitor. A multi-modular, open-label Phase I study to evaluate safety and tolerability of samuraciclib in patients with advanced malignancies was designed (ClinicalTrials.gov: NCT03363893).

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Background: Cancer is a leading cause of disease burden globally, with more than 19·3 million cases and 10 million deaths recorded in 2020. Research is crucial to understanding the determinants of cancer and the effects of interventions, and to improving outcomes. We aimed to analyse global patterns of public and philanthropic investment in cancer research.

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Purpose: The 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.

Methods: This multicentre, multinational cohort study recruited 6045 patients from the UK, Spain and Portugal during the peak pandemic period (Feb-July 2020).

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Article Synopsis
  • A James Lind Alliance partnership was formed to identify research priorities in breast cancer surgery by gathering input from those with lived experience, high genetic risk individuals, and healthcare professionals (HCPs).
  • An online survey collected uncertainties, leading to an interim survey where participants ranked their top 10 priorities, ultimately discussed in a workshop to finalize the top 10 research questions.
  • The process revealed significant differences in priorities among patients/carers, HCPs, and high-risk individuals, highlighting the need for future research to reflect the varied concerns of the breast cancer community.
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Genomic instability is a hallmark of tumourigenesis, influencing tumour development and progression. In particular, defects in the DNA damage response (DDR) have been extensively investigated and are known to shape therapeutic response. Since immune checkpoint blockade (ICB) therapy has been approved for treatment of tumours with defective mismatch repair the interplay between DDR pathway deficiency and the immune system has been of particular interest.

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Article Synopsis
  • CT900 is a new small molecule drug that inhibits thymidylate synthase and targets tumors overexpressing the α-folate receptor (α-FR).
  • In a clinical trial, doses between 1-12 mg/m2 were tested on patients with high-grade serous ovarian cancer, focusing on a dose of 12 mg/m2 given every two weeks.
  • The trial showed manageable side effects and a 21.9% overall response rate, with better outcomes in patients who had higher α-FR expression, indicating that CT900 has potential for further study.
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Purpose: Epidemiological studies have indicated a higher prevalence of hypothyroidism in breast cancer patients, possibly related to shared risk factors and breast cancer treatments. However, few studies have evaluated how hypothyroidism impacts survival outcomes in breast cancer patients. We aimed to determine the association between hypothyroidism and breast cancer-specific and all-cause mortality.

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