Wire-Free Targeted Axillary Dissection: A Pooled Analysis of 1300+ Cases Post-Neoadjuvant Systemic Therapy in Node-Positive Early Breast Cancer.

Recent advances in neoadjuvant systemic therapy (NST) have significantly improved pathologic complete response rates in early breast cancer, challenging the role of axillary lymph node dissection in nose-positive patients. Targeted axillary dissection (TAD) integrates marked lymph node biopsy (MLNB) and tracer-guided sentinel lymph node biopsy (SLNB). The introduction of new wire-free localisation markers (LMs) has streamlined TAD and increased its adoption. The primary endpoints include the successful localisation and retrieval rates of LMs. The secondary endpoints include the pathological complete response (pCR), SLNB, and MLNB concordance, as well as false-negative rates. Seventeen studies encompassing 1358 TAD procedures in 1355 met the inclusion criteria. The localisation and retrieval rate of LMs were 97% and 99%. A concordance rate of 67% (95% CI: 64-70) between SLNB and MLNB was demonstrated. Notably, 49 days (range: 0-272) was the average LM deployment time to surgery. pCR was observed in 46% (95% CI: 43-49) of cases, with no significant procedure-related complications. Omitting MLNB or SLNB would have under-staged the axilla in 15.2% or 5.4% (p = 0.0001) of cases, respectively. MLNB inclusion in axillary staging post-NST for initially node-positive patients is crucial. The radiation-free Savi Scout, with its minimal MRI artefacts, is the preferred technology for TAD.

Harnessing Micronutrient Power: Vitamins, Antioxidants and Probiotics in Breast Cancer Prevention.

Breast cancer remains a global health challenge, prompting a search for preventive strategies beyond conventional approaches. This review explores the potential of specific micronutrients, including antioxidants, vitamins, and probiotics, in breast cancer prevention. Through an extensive literature search encompassing PubMed up to March 2024, 14 micronutrients emerged with promising roles in breast cancer prevention. These include five vitamins: folate, vitamin D, vitamin B6, beta carotene, and vitamin C and nine other micronutrients: curcumin, piperine, epigallocatechin-3-gallate, quercetin, sulforaphane, indole-3-carbinol, lactobacillus, n-3 polyunsaturated fatty acids and lycopene. Understanding the efficacy of these micronutrients could pave the way for personalized preventive interventions, offering new avenues for reducing breast cancer incidence and improving public health outcomes.

Evaluating Magnetic Seed Localization in Targeted Axillary Dissection for Node-Positive Early Breast Cancer Patients Receiving Neoadjuvant Systemic Therapy: A Comprehensive Review and Pooled Analysis.

Background/Objectives: De-escalation of axillary surgery is made possible by advancements in both neoadjuvant systemic therapy (NST) and in localisation technology for breast lesions. Magseed®, developed in 2013 by Dr. Michael Douk of Cambridge, United Kingdom, is a wire-free localisation technology that facilitates the localisation and retrieval of lymph nodes for staging. Targeted axillary dissection (TAD), which entails marked lymph node biopsy (MLNB) and sentinel lymph node biopsy (SLNB), has emerged as the preferred method to assess residual disease in post-NST node-positive patients. This systematic review and pooled analysis evaluate the performance of Magseed® in TAD. Methods: The search was carried out in PubMed and Google Scholar. An assessment of localisation, retrieval rates, concordance between MLNB and SLNB, and pathological complete response (pCR) in clinically node-positive patients post NST was undertaken. Results: Nine studies spanning 494 patients and 497 procedures were identified, with a 100% successful deployment rate, a 94.2% (468/497) [95% confidence interval (CI), 93.7-94.7] localisation rate, a 98.8% (491/497) retrieval rate, and a 68.8% (247/359) [95% CI 65.6-72.0] concordance rate. pCR was observed in 47.9% (220/459) ) [95% CI 43.3-52.6] of cases. Subgroup analysis of studies reporting the pathological status of MLNB and SLNB separately revealed an FNR of 4.2% for MLNB and 17.6% for SLNB (p = 0.0013). Mean duration of implantation was 37 days (range: 0-188). Conclusions: These findings highlight magnetic seed localisation's efficacy in TAD for NST-treated node-positive patients, aiding in accurate axillary pCR identification and safe de-escalation of axillary surgery in excellent responders.

Reevaluating Axillary Lymph Node Dissection in Total Mastectomy for Low Axillary Burden Breast Cancer: Insights from a Meta-Analysis including the SINODAR-ONE Trial.

Complete axillary lymph node dissection (cALND) was previously the standard of care for breast cancer (BC) patients with axillary node disease or macro-metastases found via sentinel lymph node biopsy (SLNB). However, due to significant morbidity, contemporary management now considers a more selective approach, influenced by studies like ACOSOG Z0011. This trial showed that cALND could be omitted without compromising local control or survival in patients with low axillary nodal disease burden undergoing breast-conserving therapy, radiotherapy, and systemic therapy. The relevance of this approach for women with low axillary nodal burden undergoing total mastectomy (TM) remained unclear. A PubMed search up to September 2023 identified 147 relevant studies, with 6 meeting the inclusion criteria, involving 4184 patients with BC and low-volume axillary disease (1-3 positive lymph nodes) undergoing TM. Postmastectomy radiotherapy receipt was similar in both groups. After a mean 7.2-year follow-up, both the pooled results and the meta-analysis revealed no significant differences in overall survival. The combined analysis of the published studies, including the subgroup analysis of the SINODAR-One trial, indicates no survival advantage for cALND over SLNB in T1-T2 breast cancer patients with 1-3 positive sentinel lymph nodes (pN1) undergoing mastectomy. This suggests that, following a multidisciplinary evaluation, cALND can be safely omitted. However, the impact of other patient, tumor, and treatment factors on survival requires consideration and therefore further prospective trials are needed for conclusive validation.

Omitting Sentinel Lymph Node Biopsy after Neoadjuvant Systemic Therapy for Clinically Node Negative HER2 Positive and Triple Negative Breast Cancer: A Pooled Analysis.

Recent advances in systemic treatment for breast cancer have been underpinned by recognising and exploiting subtype-specific vulnerabilities to achieve higher rates of pathologic complete response (pCR) after neo-adjuvant systemic therapy (NAST). This down-staging of disease has permitted safe surgical de-escalation in patients who respond well. Triple-negative (TNBC) or HER2-positive breast cancer is most likely to achieve complete radiological response (rCR) and pCR after NAST. Hence, for selected patients, particularly those who are clinically node-negative (cN0) at diagnosis, the probability of disease in the sentinel node after NAST could be low enough to justify omitting axillary surgery. The aim of this pooled analysis was to determine the rate of sentinel node positivity (ypN+) in patients with TNBC or HER2-positive breast cancer who were initially cN0, achieving rCR and/or pCR in the breast after NAST. MedLine was searched using appropriate search terms. Five studies (N = 3834) were included in the pooled analysis, yielding a pooled ypN+ rate of 2.16% (95% CI: 1.70-2.63). This is significantly lower than the acceptable false negative rate of sentinel lymph node biopsy (SLNB) and supports consideration of omission of SLNB in this subset of patients.

A Comparative Safety Analysis of Medicines Based on the UK Pharmacovigilance and General Practice Prescribing Data in England.

BACKGROUND/AIM: Adverse drug reactions (ADRs) represent a major concern leading to significant increases in both morbidity and mortality globally. Providing healthcare professionals (HCPs) and patients with real-world data on drug safety is imperative to facilitate informed decision-making. The study aimed to determine the feasibility of creating comparative safety charts for medicines by mapping ADR reporting onto prescribing data. MATERIALS AND METHODS: Data on serious and fatal ADR reports from the Yellow Card database was mapped onto general practice prescription data in England. The rate of serious and fatal ADR reports per million items prescribed was calculated for commonly-prescribed medicines. RESULTS: Quantitative comparative analyses for 137 medicines belonging to 26 therapeutic classes were conducted. Significant differences were observed within most therapeutic classes for the rate of serious and fatal ADR reports per prescribing unit. CONCLUSION: Despite the limitations of ADR reporting and prescribing databases, the study provides a proof-of-concept for the feasibility of mapping ADR reporting onto prescribing data to create comparative safety charts that could support evidence-based decision-making around formulary choices.

The Role of Community Pharmacists in Addressing Medication-related Issues for Breast Cancer Patients Receiving Adjuvant Endocrine Therapy.

Breast cancer is the most common cancer in women globally. To prevent relapse and prolong disease-free survival, adjuvant endocrine treatment such as selective oestrogen receptor modulators and aromatase inhibitors are being used. However, such oestrogen-blocking agents can cause serious adverse events. Community pharmacists are ideally positioned to ensure that such adverse events are addressed promptly and competently through their comprehensive knowledge of medicines. To identify the skills and training required to improve community pharmacists' communication in breast cancer settings regarding adjuvant endocrine treatments and to propose a conceptual framework for setting up such breast cancer service, we reviewed the literature using PubMed and performed a brief survey of eight community pharmacists using semi-structured interview method. To improve pharmacists' competencies in breast cancer settings, a clear framework for the proposed service on the national level is required. In addition to communication skills training programmes and problem-solving competences, reviewing the pharmacy pre-registration training curriculum and creating appropriate platforms that monitor medications in breast cancer patients are advocated.

Pre-pectoral Immediate Breast Reconstruction Following Conservative Mastectomy Using Acellular Dermal Matrix and Semi-smooth Implants.

BACKGROUND/AIM: Improvements in acellular dermal matrix (ADM) and surgical techniques have facilitated pre-pectoral immediate breast reconstruction (IBR). Outer shell texturing is a key risk factor for anaplastic large cell lymphoma, prompting this evaluation of reconstruction with nano-textured rounded implants. PATIENTS AND METHODS: Fifty-one consecutive patients underwent 72 pre-pectoral ADM-assisted (fenestrated SurgiMend™) IBRs using nano-textured implants (Sebbin™). Patients were invited to complete a satisfaction questionnaire, including aesthetic outcome (linear scale 0-10) during follow-up. RESULTS: Average mastectomy weight was 300 g (range=83-1,018 g). After a mean follow-up of 18.3 month, 2 patients (2.8%) had minor wound complications. One patient suffered nipple necrosis. Capsular contracture occurred in 5 cases (6.9%) and significant rippling in one case. No implants were lost. Patient-reported aesthetic outcomes had a mean score of 9.3 (range=3-10; N=71). CONCLUSION: Pre-pectoral ADM-assisted IBR using semi-smooth implants following NSM is reliable and safe, with a low incidence of complications and high patient satisfaction.

Chemoprevention of Prostate Cancer by Natural Agents: Evidence from Molecular and Epidemiological Studies.

BACKGROUND/AIM: Prostate cancer is one of the most common cancers in men which remains a global public health issue. Treatment of prostate cancer is becoming increasingly intensive and aggressive, with a corresponding increase in resistance, toxicity and side effects. This has revived an interest in nontoxic and cost-effective preventive strategies including dietary compounds due to the multiple effects they have been shown to have in various oncogenic signalling pathways, with relatively few significant adverse effects. MATERIALS AND METHODS: To identify such dietary components and micronutrients and define their prostate cancer-specific actions, we systematically reviewed the current literature for the pertinent mechanisms of action and effects on the modulation of prostate carcinogenesis, along with relevant updates from epidemiological and clinical studies. RESULTS: Evidence from various recent experimental, clinical and epidemiological studies indicates that select dietary micronutrients (i.e., lycopene, epigallocatechin gallate, sulforaphane, indole-3-carbinol, resveratrol, quercetin, curcumin & piperine) and zinc play a key role in prostate cancer prevention and progression and therefore hold great promise for the future overall management of prostate cancer. CONCLUSION: A formulation that comprises these micronutrients using the optimal, safest form and dosing should be investigated in future prostate cancer chemoprevention studies and as part of standard prostate cancer therapy.

Chemoprevention of Breast Cancer With Vitamins and Micronutrients: A Concise Review.

Numerous dietary components and vitamins have been found to inhibit the molecular events and signalling pathways associated with various stages of breast cancer development. To identify the vitamins and dietary micronutrients that exert protective effects against breast cancer and define their mechanism of action, we performed a literature review of in vitro, animal and epidemiological studies and selected the in vitro and animal studies with robust molecular evidence and the epidemiological studies reporting statistically significant inverse associations for a breast cancer-specific protective effect. There is sufficient evidence from in vitro, animal and epidemiological human studies that certain vitamins, such as vitamin D3, folate, vitamin B6, and beta carotene as well as dietary micronutrients, such as curcumin, piperine, sulforaphane, indole-3-carbinol, quercetin, epigallocatechin gallate (EGCG) and omega-3 polyunsaturated fatty acids (PUFAs), display an antitumoral activity against breast cancer and have the potential to offer a natural strategy for breast cancer chemoprevention and reduce the risk of breast cancer recurrence. Therefore, a supplement that contains these micronutrients, using the safest form and dosage should be investigated in future breast cancer chemoprevention studies and as part of standard breast cancer therapy.

The Impact of EndoPredict Clinical Score on Chemotherapy Recommendations in Women with Invasive ER+/HER2- Breast Cancer Stratified as Having Moderate or Poor Prognosis by Nottingham Prognostic Index.

BACKGROUND: The Nottingham Prognostic Index (NPI) was developed using tumour pathological features to guide decisions regarding adjuvant therapy in breast cancer. Recent breakthroughs in molecular biology aided development of genomic assays such as EndoPredict, which have been shown to provide excellent prognostic information. The current study investigated the impact of EndoPredict Clinical (EPClin), a composite of clinicopathological data and EndoPredict score, on chemotherapy recommendations based on NPI. PATIENTS AND METHODS: A total of 120 patients with oestrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer who were candidates for post-operative adjuvant chemotherapy at a single tertiary centre were included. Both NPI and EPClin were applied to all patients. NPI differentiated patients into groups with excellent/good prognosis (N=41; NPI≤3.4) or moderate/poor prognosis (N=79; NPI >3.4). The latter were considered for adjuvant chemotherapy. RESULTS: There was discordance in results of 31% of cases; 35% of the patients/candidates for adjuvant chemotherapy according to NPI were reclassified as being at low risk of recurrence by EPClin. CONCLUSION: Genomic profiling using EPClin reduces the potential need for adjuvant chemotherapy in women with ER+/HER2- breast cancer who are candidates for chemotherapy according to the NPI.

Do online prognostication tools represent a valid alternative to genomic profiling in the context of adjuvant treatment of early breast cancer? A systematic review of the literature.

INTRODUCTION: Decision-making regarding adjuvant chemotherapy has been based on clinical and pathological features. However, such decisions are seldom consistent. Web-based predictive models have been developed using data from cancer registries to help determine the need for adjuvant therapy. More recently, with the recognition of the heterogenous nature of breast cancer, genomic assays have been developed to aid in the therapeutic decision-making. METHODS: We have carried out a comprehensive literature review regarding online prognostication tools and genomic assays to assess whether online tools could be used as valid alternatives to genomic profiling in decision-making regarding adjuvant therapy in early breast cancer. RESULTS AND CONCLUSIONS: Breast cancer has been recently recognized as a heterogenous disease based on variations in molecular characteristics. Online tools are valuable in guiding adjuvant treatment, especially in resource constrained countries. However, in the era of personalized therapy, molecular profiling appears to be superior in predicting clinical outcome and guiding therapy.

A Comparison of the Performance of EndoPredict Clinical and NHS PREDICT in 120 Patients Treated for ER-positive Breast Cancer.

BACKGROUND: Computational algorithms, such as NHS PREDICT, have been developed using cancer registry data to guide decisions regarding adjuvant chemotherapy. They are limited by biases of the underlying data. Recent breakthroughs in molecular biology have aided the development of genomic assays which provide superior clinical information. In this study, we compared the performance in risk stratification of EndoPredict Clinical (EPClin, a composite of clinical data and EndoPredict) and PREDICT in a cohort of patients with breast cancer considered potential candidates for chemotherapy by the clinicians. MATERIALS AND METHODS: One hundred and twenty patients with biopsy-proven oestrogen receptor positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer who underwent surgery were included. EPClin and PREDICT were determined for every tumour, and the results were compared. RESULTS: Using EPClin scores performed on 120 tumours, the cohort was stratified into low- (n=60) and high-risk (n=60) groups leading to 50% reduction in total chemotherapy prescriptions. PREDICT differentiated the patients into low- (n=45), intermediate- (n=33), and high-risk groups (n=42). Discordance between scores was demonstrated for 50 (41.66%) tumours. Nine (20%) out of 45 patients with low PREDICT scores had high EPClin scores and would otherwise not have received chemotherapy if the NHS PREDICT tool had been used alone. Eight (19%) out of 42 patients at high risk by PREDICT were reclassified as being at low risk by EPClin and avoided adjuvant chemotherapy. The sensitivity, specificity, positive predictive value and negative predictive value for NHS PREDICT to predict the potential need for chemotherapy as determined by EPClin were 85%, 51%, 68% and 80%, respectively. CONCLUSION: To our knowledge, this is the first clinical study to compare EPClin and PREDICT. The data indicate that computational algorithms such as NHS PREDICT may not accurately predict the need for chemotherapy leading to overtreatment, undertreatment or uncertainty and anxiety in a significant proportion of patients. This underscores the importance of more personalized prognostic tools.

Are online prediction tools a valid alternative to genomic profiling in the context of systemic treatment of ER-positive breast cancer?

BACKGROUND: Clinicians use clinical and pathological parameters, such as tumour size, grade and nodal status, to make decisions on adjuvant treatments for breast cancer. However, therapeutic decisions based on these features tend to vary due to their subjectivity. Computational and mathematical algorithms were developed using clinical outcome data from breast cancer registries, such as Adjuvant! Online and NHS PREDICT. More recently, assessments of molecular profiles have been applied in the development of better prognostic tools. METHODS: Based on the available literature on online registry-based tools and genomic assays, we evaluated whether these online tools could be valid and accurate alternatives to genomic and molecular profiling of the individual breast tumour in aiding therapeutic decisions, particularly in patients with early ER-positive breast cancer. RESULTS AND CONCLUSIONS: Early breast cancer is currently considered a systemic disease and a complex ecosystem with behaviour determined by the complex genetic and molecular signatures of the tumour cells, mammary stem cells, microenvironment and host immune system. We anticipate that molecular profiling will continue to evolve, expanding beyond the primary tumour to include the tumour microenvironment, cancer stem cells and host immune system. This should further refine therapeutic decisions and optimise clinical outcome. This article was specially invited by the editors and represents work by leading researchers.