Abemaciclib Therapy Using the MonarchE Criteria Results in Large Numbers of Excess Axillary Node Clearances-Time to Pause and Reflect?

The monarchE study added the CDK4/6 inhibitor abemaciclib to the care of women with oestrogen-positive (ER+) breast cancers. Eligibility required meeting monarchE criteria-either >3 positive axillary nodes, or 1-3 positive sentinel nodes (SNB+) with tumour size >50 mm or grade 3 cancers. Women were advised to proceed to completion axillary node clearance (cANC) if size/grade criteria were not fulfilled for >3 positive nodes to be identified. However, cANC is associated with significant morbidity, conflicting with the potential benefits of abemaciclib. We analysed data of 229 consecutive women (2016-2022) with ER+ breast cancer and SNB+ who proceeded to cANC, keeping with contemporary treatment guidelines. We used this cohort to assess numbers that, under national guidance in place currently, would be advised to undergo cANC solely to check eligibility for abemaciclib treatment. Using monarchE criteria, 90 women (39%) would have accessed abemaciclib based on SNB+ and size/grade, without cANC. In total, 139 women would have been advised to proceed to cANC to check eligibility, with only 15/139 (11%) having >3 positive nodes after sentinel node biopsy and cANC. The remaining 124 (89%) would have undergone cANC but remained ineligible for abemaciclib. Size, age, grade, and Ki67 did not predict >3 nodes at cANC. Following cANC, a large majority of women with ER+, <50 mm, and grade 1-2 tumours remain ineligible for abemaciclib yet are subject to significant morbidity including lifelong lymphoedema risk. The monarchE authors state that 15 women need abemaciclib therapy for 1 to clinically benefit. Thus, in our cohort, 139 women undergoing cANC would lead to one woman benefitting.

Results of shared learning of a new radiofrequency identification localization device-a UK iBRA-NET breast cancer localisation study.

INTRODUCTION: Localisation methods for surgical excision of impalpable breast lesions have advanced in recent years, with increasing utilization of new wire-free technologies. The Hologic LOCalizer™ radiofrequency identification (RFID) tag is one such device; however, as is the case when new technologies are first introduced, little is known about clinical experiences, potential complications, and learning used to overcome perioperative challenges when changing from guidewires to RFID tags. This study reports shared learning experiences of clinicians using the LOCalizer™ as part of the national iBRA-NET localisation study. METHODS: This mixed-methods study captured shared-learning themes relating to LOCalizer™ usage as part of a multicentre prospective registry study, which collected data on each LOCalizer™ placement. Prospective, anonymized clinical and demographic data were collected and managed using a Research Electronic Data Capture (REDCap) database. Shared learning was captured prospectively as part of the registry study between January 2021 and July 2022, combined with a virtual qualitative webinar-style focus group. Learning events were then coded, grouped by theme, and suggestions for practice were produced. RESULTS: Twenty-four UK breast units submitted data on 1188 patient records pertaining to RFID-guided localisation between January 2021 and July 2022, of which 59 (5.0%) included a shared-learning event. The virtual webinar was attended by 108 healthcare professionals, including oncoplastic breast surgeons and breast radiologists. Shared-learning themes were categorized into preoperative, intraoperative, and postoperative events. CONCLUSIONS: By sharing learning outcomes associated with localisation techniques in this paper, the aim is to shorten the learning curve and potential for adverse events for users new to the LOCalizer™ technique.

Breast cancer research gaps: a questionnaire-based study to determine overall priorities and compare the priorities of patients, the public, clinicians and scientists.

OBJECTIVE: This study aims to prioritise the themes identified from the three gap analyses performed by a combination of scientists, clinicians, patients and members of the public to determine areas in breast cancer care where research is lacking. We also aimed to compare the priorities of areas of agreed research need between patients, the public, clinicians and scientists. DESIGN: A cross-section of patients, public, clinicians and scientists completed a prioritisation exercise to rank the identified themes where research is lacking in breast cancer care. PARTICIPANTS: Patients, clinicians and scientists who have experienced, managed or worked in the field of breast cancer and members of the public. METHODS: The research areas identified in the Breast Cancer Campaign, Association of Breast Surgery and North West Breast Research Collaborative gap analyses were outlined as 22 themes in lay terminology. Patients, members of the public, clinicians and scientists were invited to complete the prioritisation exercise, on paper or electronically, ranking the themes from 1 to 22. Comparisons were made with arithmetic mean ranking. RESULTS: Of the 510 prioritisation exercises completed, 179 (35%) participants were patients, 162 (32%) public, 43 (8%) scientists and 122 (24%) clinicians. The theme ranked of highest priority overall was 'better prevention' (arithmetic mean rank 6.4 (SE 0.23)). 'Better prevention' was ranked top or second by patients, public and clinicians (7 (0.39), 4.7 (0.34) and 6.8 (0.5), respectively), however, scientists ranked this as their sixth most important factor (7.7 (0.92)). The public and clinicians had good agreement with patients (r=0.84 and r=0.75, respectively), whereas scientists had moderate agreement with patients (r=0.65). Certain themes were ranked significantly differently by participant groups. Compared with clinicians, patients prioritised research into 'alternative to mammograms', 'diagnostic (cancer) blood test' and 'rare cancers' (OR 2.1 (95% CI 1.3 to 3.5), p=0.002, OR 2.1 (95% CI 1.3 to 3.5), p=0.004 and OR 1.7 (95% CI 1.1 to 2.8), p=0.03). Compared with scientists, patients deprioritised 'better laboratory models' (OR 0.4 (95% CI 0.2 to 0.8), p=0.01). CONCLUSION: This study demonstrates that patients, public, clinicians and scientists have different research priorities, with scientists being a particular outlier. This highlights the need to ensure the engagement of patients and public in research funding prioritisation decisions.

Bridging pre-surgical endocrine therapy for breast cancer during the COVID-19 pandemic: outcomes from the B-MaP-C study.

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). 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. RESULTS: 1094 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. DISCUSSION: This 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.

Results of shared learning of a new magnetic seed localisation device - A UK iBRA-NET breast cancer localisation study.

INTRODUCTION: Shared learning is imperative in the assessment and safe implementation of new healthcare interventions. Magnetic seeds (Magseed®) potentially offer logistical benefit over wire localisation for non-palpable breast lesions but few data exist on outcomes comparing these techniques. A national registration study (iBRA-NET) was conducted to collate device outcomes. In order to share learning, thematic analysis was conducted to ascertain early clinical experiences of Magseed® and wire guided localisation and explore how learning events may be applied to improve clinical outcomes. METHODS: A qualitative study of 27 oncoplastic surgeons, radiologists and physicians was conducted in January 2020 to ascertain the feasibility and challenges associated with Magseed® versus wire breast localisation surgery. Four focus groups were asked to discuss experiences, concerns and shared learning outcomes which were tabulated and analysed thematically. RESULTS: Three key themes were identified comparing Magseed® and wire localisation of breast lesions relating to preoperative, intraoperative and postoperative learning outcomes. Percutaneous Magseed® detection, instrument interference and potential seed or wire dislodgement were the most common issues identified. Clinician experience suggested Magseed® index lesion identification was non-inferior to wire placement and improved the patient pathway in terms of scheduling and multi-site insertion. CONCLUSIONS: Prospective shared learning suggested Magseed® offered additional non-clinical benefits over wire localisation, improving the efficiency of the patient pathway. Recommendations for improving breast localisation technique, appropriate patient selection and clinical practice through shared learning are discussed that may aid other surgeons in the adoption of this relatively new technique.

The Kenya UK Breast Cancer Awareness Week: curriculum codesign and codelivery with direct and lived experience of breast cancer diagnosis and management.

Global health education holds a paradox: the provision of global health degrees focusing on challenges in low-income and middle-income countries has increased in high-income countries, while those in these low-income and middle-income countries lack access to contribute their expertise, creating an 'information problem'. Breast cancer is a pressing global health priority, which requires curriculum design, implementation, ownership and leadership by those with direct and lived experience of breast cancer.The Kenya-UK Breast Cancer Awareness Week was conceptualised following the signing of the Memorandum of Understanding between the Kenyan and UK governments launching the Kenya UK Health Alliance. This alliance aims to promote health cooperation to address Kenya's breast cancer challenge. Here, we present the first of the collaborative's initiatives: a breast cancer global health education programme designed, implemented, owned and led by Kenyan stakeholders.We present the utilisation of the Virtual Roundtable for Collaborative Education Design for the design and implementation of a nationwide virtual breast cancer awareness week delivered across eleven Kenyan medical schools. By involving partners with lived and/or professional experience of breast cancer in Kenya in all stages of the design and delivery of the awareness week, the project experimented with disrupting power dynamics and fostered ownership of the initiative by colleagues with direct expertise of breast cancer in Kenya.This initiative provides a platform, precedent and playbook to guide professionals from other specialties in the design and implementation of similar global collaborative ventures. We have used this approach to continue to advocate for global health curricula design change, so that those with lived experiences of global health challenges in their contextualised professional and personal environments are given leadership, reward and ownership of their curricula and further to highlight breast cancer as a global heath priority.

Neoadjuvant Intravenous Oncolytic Vaccinia Virus Therapy Promotes Anticancer Immunity in Patients.

Improving the chances of curing patients with cancer who have had surgery to remove metastatic sites of disease is a priority area for cancer research. Pexa-Vec (Pexastimogene Devacirepvec; JX-594, TG6006) is a principally immunotherapeutic oncolytic virus that has reached late-phase clinical trials. We report the results of a single-center, nonrandomized biological end point study (trial registration: EudraCT number 2012-000704-15), which builds on the success of the presurgical intravenous delivery of oncolytic viruses to tumors. Nine patients with either colorectal cancer liver metastases or metastatic melanoma were treated with a single intravenous infusion of Pexa-Vec ahead of planned surgical resection of the metastases. Grade 3 and 4 Pexa-Vec-associated side effects were lymphopaenia and neutropaenia. Pexa-Vec was peripherally carried in plasma and was not associated with peripheral blood mononuclear cells. Upon surgical resection, Pexa-Vec was found in the majority of analyzed tumors. Pexa-Vec therapy associated with IFNα secretion, chemokine induction, and resulted in transient innate and long-lived adaptive anticancer immunity. In the 2 patients with significant and complete tumor necrosis, a reduction in the peripheral T-cell receptor diversity was observed at the time of surgery. These results support the development of presurgical oncolytic vaccinia virus-based therapies to stimulate anticancer immunity and increase the chances to cure patients with cancer.

Wire- and magnetic-seed-guided localization of impalpable breast lesions: iBRA-NET localisation study.

BACKGROUND: Wire localization is historically the most common method for guiding excision of non-palpable breast lesions, but there are limitations to the technique. Newer technologies such as magnetic seeds may allow some of these challenges to be overcome. The aim was to compare safety and effectiveness of wire and magnetic seed localization techniques. METHODS: Women undergoing standard wire or magnetic seed localization for non-palpable lesions between August 2018 and August 2020 were recruited prospectively to this IDEAL stage 2a/2b platform cohort study. The primary outcome was effectiveness defined as accurate localization and removal of the index lesion. Secondary endpoints included safety, specimen weight and reoperation rate for positive margins. RESULTS: Data were accrued from 2300 patients in 35 units; 2116 having unifocal, unilateral breast lesion localization. Identification of the index lesion in magnetic-seed-guided (946 patients) and wire-guided excisions (1170 patients) was 99.8 versus 99.1 per cent (P = 0.048). There was no difference in overall complication rate. For a subset of patients having a single lumpectomy only for lesions less than 50 mm (1746 patients), there was no difference in median closest margin (2 mm versus 2 mm, P = 0.342), re-excision rate (12 versus 13 per cent, P = 0.574) and specimen weight in relation to lesion size (0.15 g/mm2versus 0.138 g/mm2, P = 0.453). CONCLUSION: Magnetic seed localization demonstrated similar safety and effectiveness to those of wire localization. This study has established a robust platform for the comparative evaluation of new localization devices.

No association between breast pain and breast cancer: a prospective cohort study of 10 830 symptomatic women presenting to a breast cancer diagnostic clinic.

BACKGROUND: Women with breast pain constitute >20% of breast clinic attendees. AIM: To investigate breast cancer incidence in women presenting with breast pain and establish the health economics of referring women with breast pain to secondary care. DESIGN AND SETTING: A prospective cohort study of all consecutive women referred to a breast diagnostic clinic over 12 months. METHOD: Women were categorised by presentation into four distinct clinical groups and cancer incidence investigated. RESULTS: Of 10 830 women, 1972 (18%) were referred with breast pain, 6708 (62%) with lumps, 480 (4%) with nipple symptoms, 1670 (15%) with 'other' symptoms. Mammography, performed in 1112 women with breast pain, identified cancer in eight (0.7%). Of the 1972 women with breast pain, breast cancer incidence was 0.4% compared with ∼5% in each of the three other clinical groups. Using 'breast lump' as reference, the odds ratio (OR) of women referred with breast pain having breast cancer was 0.05 (95% confidence interval = 0.02 to 0.09, P<0.001). Compared with reassurance in primary care, referral was more costly (net cost £262) without additional health benefits (net quality-adjusted life-year [QALY] loss -0.012). The greatest impact on the incremental cost-effectiveness ratio (ICER) was when QALY loss because of referral-associated anxiety was excluded. Primary care reassurance no longer dominated, but the ICER remained greater (£45 528/QALY) than typical UK National Health Service cost-effectiveness thresholds. CONCLUSION: This study shows that referring women with breast pain to a breast diagnostic clinic is an inefficient use of limited resources. Alternative management pathways could improve capacity and reduce financial burden.

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

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.

Impalpable breast lesion localisation, a logistical challenge: results of the UK iBRA-NET national practice questionnaire.

INTRODUCTION: Breast conserving surgery of impalpable breast lesions requires safe and effective localisation techniques. Wire localisation has traditionally been used, but has limitations. Newer techniques are now being introduced to mitigate this. The iBRA-NET group aims to robustly evaluate these new techniques in well-designed prospective studies. We report the first phase of this evaluation, a survey to establish current practice and service provision of breast localisation techniques in the UK. METHODS: A national practice questionnaire was designed using 'SurveyMonkey®' and was circulated to UK breast surgeons via the Association of Breast Surgery and the Mammary Fold. The questionnaire was live from 6th October 2018 to 6th April 2019. Only one response per unit was requested to reflect the unit's practice. RESULTS: Complete responses were received from 98 breast units across the UK. Wires were the mostly commonly used localisation technique (n = 82) with fewer units using Magseed® (n = 9), Radioguided Occult Lesion Localisation (n = 5) and Radioiodine Seed Localisation (n = 2). There was significant variation in practice and logistics involved. Frequent delays and theatre overruns were reported in 39 and 16 units, respectively. The median satisfaction score of the current technique was 7 out of 10. The main perceived limitation of existing localisation methods was logistics affecting theatre scheduling and the main barrier to introducing a new technique was cost. CONCLUSION: Wires are currently the most commonly used localisation technique but are associated with significant logistical issues. Newer techniques may offer a better solution but will need robust evaluation before they are adopted to ensure safety and efficacy.

The B-MaP-C study: Breast cancer management pathways during the COVID-19 pandemic. Study protocol.

INTRODUCTION: Approximately 55,000 women in the United Kingdom are diagnosed with new breast cancer annually. Since emerging in December 2019, SARS-CoV-2 (coronavirus disease 2019, COVID-19) has become a global pandemic, affecting healthcare delivery worldwide. In response to the pandemic, multiple guidelines were issued to assist with rationalising breast cancer care. The primary aim of the B-MaP-C study is to audit and describe breast cancer management of patients newly diagnosed with breast cancer during the COVID-19 pandemic against pre-COVID-19 management practice in the UK. The implications of changes to management will be determined and the impact of a COVID-19 diagnosis on the patient's breast cancer management will be determined. METHODS AND ANALYSIS: This is a multi-centre collaborative audit of consecutive breast cancer patients undergoing treatment decisions during the acute and recovery phases of the COVID-19 pandemic. All patients with newly diagnosed primary breast cancer, whose treatment was decided in a multidisciplinary meeting from the 16th March 2020, are eligible for inclusion. ETHICS AND DISSEMINATION: As this is an audit ethical approval is not required. Each participating centre is required to register the study locally and obtain local governance approvals prior to commencement of data collection. Local audit data will be available to individual participating units for governance purposes. The results of the data analysis will be submitted for publication, as well as disseminated via the ABS newsletter and a webinar. All data will be presented at national and international conferences, circumstances permitting. REGISTRATION DETAILS: Each participating centre received local governance audit registration.

Radioactive iodine ablation post differentiated thyroid cancer surgery: an analysis of use and impact of the American Thyroid Association guidelines.

BACKGROUND: The 2009 American Thyroid Association (ATA) three-tiered risk stratification, and its updated version in 2015, provided clearer guidance on the use of radioactive iodine (RAI) ablation in differentiated thyroid cancer (DTC) patients. This study examines the impact of these guidelines on RAI use in our institution. METHODS: Patients diagnosed with DTC during three different time periods (group 1: 2002-2006, group 2: 2010-2014 and group 3: 2017-2018) were identified and risk stratified according to the ATA guidelines. RAI use and extent of surgery were compared between the three groups. Categorical variables were analysed using Fisher's exact (2 × 2) and chi-squared (>2 × 2) tests. RESULTS: A total of 415 patients were included (group 1 = 88, group 2 = 215, group 3 = 112). The proportion of patients having total thyroidectomy were 84.6, 84.7 and 69.6% in groups 1, 2 and 3, respectively (P = 0.003). Central lymph node dissection was significantly higher in the more contemporary groups compared to group 1 (9.1 versus 41.9 versus 64.3%, P < 0.001). Overall, fewer patients received RAI in more recent times (76.6 versus 54.8 versus 26.8%, P < 0.001), most evident in the low-risk patients (70 versus 29.1 versus 5.1%, P < 0.001). In the high risk group, the majority received RAI, with no difference between the groups. CONCLUSION: Comparing DTC patients treated in our unit before and after publications of the 2009 and 2015 ATA guidelines, more nodal surgery was performed with less RAI administered in the latter groups. Better risk stratification according to the ATA guidelines has allowed more judicious use of RAI ablation.

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study.

BACKGROUND: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. METHODS: Consecutive women undergoing mastectomy ± IBR for breast cancer July-December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. RESULTS: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. CONCLUSIONS: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients.