Extracellular Vesicle DNA Extraction and Sequencing in Ancient Serum Samples From Patients With Breast Cancer.

BACKGROUND/AIM: Extracellular vesicle DNA (EV-DNA) has emerged as a novel biomarker for tumor mutation detection using liquid biopsies, exhibiting biological advantages compared to cell-free DNA (cfDNA). This study assessed the feasibility of EV-DNA and cfDNA extraction and sequencing in old serum samples of patients with breast cancer (BC). PATIENTS AND METHODS: A total of 28 serum samples of 27 patients with corresponding clinical information were collected between 1983 and 1991. EV-DNA was extracted using Exo-GAG kit (Nasabiotech) and cfDNA using QIAsymphony DSP Virus/Pathogen Midi Kit (Qiagen), respectively. Subsequently, 10 matched samples (EV-DNA n=5, cfDNA n=5) of five patients were subjected to sequencing using the Oncomine™ Breast cfDNA Research Assay v2 (Thermo Fisher Scientific). RESULTS: Samples were collected on median 1.9 years after primary diagnosis [interquartile range (IQR)=0.2-7.2]. Median follow-up was 9.5 years (IQR=5.2-14.2). Median age of serum samples was 36.1 years (IQR=34.5-37.3). EV-DNA and cfDNA were extracted from 100% (28/28) of the included samples. Both, DNA quantity and concentration were comparable between EV-DNA and cfDNA. Sequencing was successfully performed in 100% (10/10) of the included samples. Two matched analyses yielded equivalent results in EV-DNA and cfDNA (no mutations, n=1; PIK3CA mutation, n=1), whilst in two analyses, PIK3CA mutation was only found in cfDNA, and in one analysis, a TP53 mutation was only found in EV-DNA. CONCLUSION: EV-DNA extraction and sequencing in old serum samples of patients with BC is feasible and has the potential to address clinically relevant questions in longitudinal studies.

Association of relative resection volume with patient-reported outcomes applying different levels of oncoplastic breast conserving surgery - A retrospective cohort study.

INTRODUCTION: The American Society of Breast Surgeons (ASBrS) recently classified oncoplastic breast conserving surgery (OBCS) into two levels. The association of resection ratio during OBCS with patient-reported outcomes (PRO) is unclear. MATERIALS AND METHODS: Patients with stage 0-III breast cancer undergoing OBCS between 01/2011-04/2023 at a Swiss university hospital, who completed at least one postoperative BREAST-Q PRO questionnaire were identified from a prospectively maintained institutional database. Outcomes included differences in PROs between patients after ASBrS level I (<20 % of breast tissue removed) versus level II surgery (20-50 %). RESULTS: Of 202 eligible patients, 129 (63.9 %) underwent level I OBCS, and 73 (36.1 %) level II. Six patients (3.0 %) who underwent completion mastectomy were excluded. The median time to final PROs was 25.4 months. Patients undergoing ASBrS level II surgery were more frequently affected by delayed wound healing (p < 0.001). ASBrS level was not found to independently predict any BreastQ domain. However, delayed wound healing was shown to reduce short-term physical well-being (estimated difference -26.27, 95 % confidence interval [CI] -39.33 to -13.22, p < 0.001). Higher age was associated with improved PROs. CONCLUSION: ASBrS level II surgery allows the removal of larger tumors without impairing PROs. Preventive measures for delayed wound healing and close postoperative follow-up to promptly treat wound healing disorders may avoid short-term reductions in physical well-being.

Personalizing Locoregional Therapy in Patients With Breast Cancer in 2024: Tailoring Axillary Surgery, Escalating Lymphatic Surgery, and Implementing Evidence-Based Hypofractionated Radiotherapy.

The management of axillary lymph nodes in breast cancer is continually evolving. Recent data now support omitting axillary lymph node dissection (ALND) in most patients with metastases in up to two sentinel lymph nodes (SLNs) during upfront surgery and those with residual isolated tumor cells after neoadjuvant chemotherapy (NACT). In the upfront surgery setting, ALND is still indicated, however, in patients with clinically node-positive breast cancer or more than two positive SLNs and, after NACT, in case of residual micrometastases and macrometastases. Omission of the sentinel lymph node biopsy (SLNB) can be considered in many postmenopausal patients with small luminal breast cancer, particularly when axillary ultrasound is negative. Several randomized controlled trials (RCTs) are currently aiming at eliminating the remaining indications for ALND and also establishing omission of SLNB in a broader patient population. The movement to deescalate axillary staging is in part because of the association between ALND and lymphedema, which is swelling of an extremity because of lymphatic damage and obstructed lymphatic drainage. To reduce the risk of developing this condition, patients undergoing ALND can undergo reverse mapping of the axilla and immediate reconstruction or bypass of the lymphatics from the involved extremity. Decongestion and compression are the foundation of conservative treatment for established lymphedema, while lymphovenous bypass and lymph node transfer are surgical procedures to address the physiologic dysfunction. Radiotherapy is an essential component of breast locoregional therapy: more than three decades of radiation research has optimized treatment according to patient's risk of local recurrence while substantially reducing the number of treatment visits. High-quality RCTs have shown the efficacy and safety of hypofractionation-more than 2Gy radiation dose per treatment (fraction)-significantly reducing the burden of radiotherapy treatment for many patients with breast cancer. In 2024, guidelines recommend no more than 15-16 fractions for whole-breast and nodal radiotherapy, with some recommending five fractions for whole-breast radiotherapy. In addition, simultaneous integrated boost (SIB) has been shown to be noninferior to sequential boost with regards to ipsilateral breast tumor recurrence with similar or reduced long-term side effects, also reducing overall treatment length. Further RCTs are underway investigating other indications for five fractions, including SIB and regional node irradiation, such that, in future, it may be possible for the majority of breast radiotherapy patients to be treated with a 1-week course. This manuscript serves to outline the latest updates on axillary surgical staging, lymphatic surgery, and evidence-based radiotherapy in the treatment of breast cancer.

Axillary Surgery for Breast Cancer in 2024.

Axillary surgery for patients with breast cancer (BC) in 2024 is becoming increasingly specific, moving away from the previous 'one size fits all' radical approach. The goal is to spare morbidity whilst maintaining oncologic safety. In the upfront surgery setting, a first landmark randomized controlled trial (RCT) on the omission of any surgical axillary staging in patients with unremarkable clinical examination and axillary ultrasound showed non-inferiority to sentinel lymph node (SLN) biopsy (SLNB). The study population consisted of 87.8% postmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative BC. Patients with clinically node-negative breast cancer and up to two positive SLNs can safely be spared axillary dissection (ALND) even in the context of mastectomy or extranodal extension. In patients enrolled in the TAXIS trial, adjuvant systemic treatment was shown to be similar with or without ALND despite the loss of staging information. After neoadjuvant chemotherapy (NACT), targeted lymph node removal with or without SLNB showed a lower false-negative rate to determine nodal pathological complete response (pCR) compared to SLNB alone. However, oncologic outcomes do not appear to differ in patients with nodal pCR determined by either one of the two concepts, according to a recently published global, retrospective, real-world study. Real-world studies generally have a lower level of evidence than RCTs, but they are feasible quickly and with a large sample size. Another global real-world study provides evidence that even patients with residual isolated tumor cells can be safely spared from ALND. In general, few indications for ALND remain. Three randomized controlled trials are ongoing for patients with clinically node-positive BC in the upfront surgery setting and residual disease after NACT. Pending the results of these trials, ALND remains indicated in these patients.

Prognostic Importance of Axillary Lymph Node Response to Neoadjuvant Systemic Therapy on Axillary Surgery in Breast Cancer-A Single Center Experience.

Neoadjuvant systemic treatment (NST) is the standard treatment for HER2+, triple-negative (TN), and highly proliferative luminal HER2- early breast cancer. Pathologic complete response (pCR) after NST is associated with improved outcomes. We evaluated the predictive factors for axillary-pCR (AXpCR) and its impact on the extent of axillary node surgery. This retrospective study included 92 patients (median age of 50.4 years) with an initially node-positive disease. Patients were treated with molecular subtype-specific NST (4.3% were luminal A-like, 28.3% luminal HER2-, 26.1% luminal HER2+, 18.5% HER2+ non-luminal, and 22.8% TN). Axillary-, breast- and total-pCR were achieved in 52.2%, 48.9%, and 38% of patients, respectively. In a binary logistic regression model for the whole population, the only independent factor significantly associated with AXpCR was breast-pCR (OR 7.4; 95% CI 2.6-20.9; p < 0.001). In patients who achieved breast-pCR, aggressive subtypes (HER2+ and TN; OR 11.24) and clinical tumor stage (OR 0.10) had a significant impact on achieving AXpCR. Axillary lymph node dissection was avoided in 53.3% of patients. In conclusion, in node-positive patients with HER2+ and TN subtypes, who achieved breast-pCR after NST, de-escalation of axillary surgery could be considered in most cases.

Understanding the Electronic Transport of Al-Si and Al-Ge Nanojunctions by Exploiting Temperature-Dependent Bias Spectroscopy.

Understanding the electronic transport of metal-semiconductor heterojunctions is of utmost importance for a wide range of emerging nanoelectronic devices like adaptive transistors, biosensors, and quantum devices. Here, we provide a comparison and in-depth discussion of the investigated Schottky heterojunction devices based on Si and Ge nanowires contacted with pure single-crystal Al. Key for the fabrication of these devices is the selective solid-state metal-semiconductor exchange of Si and Ge nanowires into Al, delivering void-free, single-crystal Al contacts with flat Schottky junctions, distinct from the bulk counterparts. Thereof, a systematic comparison of the temperature-dependent charge carrier injection and transport in Si and Ge by means of current-bias spectroscopy is visualized by 2D colormaps. Thus, it reveals important insights into the operation mechanisms and regimes that cannot be exploited by conventional single-sweep output and transfer characteristics. Importantly, it was found that the Al-Si system shows symmetric effective Schottky barrier (SB) heights for holes and electrons, whereas the Al-Ge system reveals a highly transparent contact for holes due to Fermi level pinning close to the valence band with charge carrier injection saturation due to a thinned effective SB. Moreover, thermionic field emission limits the overall electron conduction, indicating a distinct SB for electrons.

Impact of Imaging-Guided Localization on Performance of Tailored Axillary Surgery in Patients with Clinically Node-Positive Breast Cancer: Prospective Cohort Study Within TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

BACKGROUND: Tailored axillary surgery (TAS) is a novel surgical concept for clinical node-positive breast cancer. It consists of the removal of the sentinel lymph nodes (LNs), as well as palpably suspicious nodes. The TAS technique can be utilized in both the upfront and neoadjuvant chemotherapy (NACT) setting. This study assessed whether/how imaging-guided localization (IGL) influenced TAS. PATIENTS AND METHODS: This was a prospective observational cohort study preplanned in the randomized phase-III OPBC-03/TAXIS trial. IGL was performed at the surgeon's discretion for targeted removal of LNs during TAS. Immediate back-up axillary lymph node dissection (ALND) followed TAS according to TAXIS randomization. RESULTS: Five-hundred patients were included from 44 breast centers in six countries, 151 (30.2%) of whom underwent NACT. IGL was performed in 84.4% of all patients, with significant variation by country (77.6-100%, p < 0.001). No difference in the median number of removed (5 vs. 4, p = 0.3) and positive (2 vs. 2, p = 0.6) LNs by use of IGL was noted. The number of LNs removed during TAS with IGL remained stable over time (p = 0.8), but decreased significantly without IGL, from six (IQR 4-6) in 2019 to four (IQR 3-4) in 2022 (p = 0.015). An ALND was performed in 249 patients, removing another 12 (IQR 9-17) LNs, in which a median number of 1 (IQR 0-4) was positive. There was no significant difference in residual nodal disease after TAS with or without IGL (68.0% vs. 57.6%, p = 0.2). CONCLUSIONS: IGL did not significantly change either the performance of TAS or the volume of residual nodal tumor burden. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03513614.

Single-cell Analysis Reveals Inter- and Intratumour Heterogeneity in Metastatic Breast Cancer.

Metastasis is the leading cause of cancer-related deaths of breast cancer patients. Some cancer cells in a tumour go through successive steps, referred to as the metastatic cascade, and give rise to metastases at a distant site. We know that the plasticity and heterogeneity of cancer cells play critical roles in metastasis but the precise underlying molecular mechanisms remain elusive. Here we aimed to identify molecular mechanisms of metastasis during colonization, one of the most important yet poorly understood steps of the cascade. We performed single-cell RNA-Seq (scRNA-Seq) on tumours and matched lung macrometastases of patient-derived xenografts of breast cancer. After correcting for confounding factors such as the cell cycle and the percentage of detected genes (PDG), we identified cells in three states in both tumours and metastases. Gene-set enrichment analysis revealed biological processes specific to proliferation and invasion in two states. Our findings suggest that these states are a balance between epithelial-to-mesenchymal (EMT) and mesenchymal-to-epithelial transitions (MET) traits that results in so-called partial EMT phenotypes. Analysis of the top differentially expressed genes (DEGs) between these cell states revealed a common set of partial EMT transcription factors (TFs) controlling gene expression, including ZNF750, OVOL2, TP63, TFAP2C and HEY2. Our data suggest that the TFs related to EMT delineate different cell states in tumours and metastases. The results highlight the marked interpatient heterogeneity of breast cancer but identify common features of single cells from five models of metastatic breast cancer.

[New treatment options in system therapy for breast carcinoma and associated new side effects].

INTRODUCTION: Breast cancer today has a significantly better prognosis than two to three decades ago. Treatment options have improved significantly. However, new systemic therapy has also resulted in side effects that clinicians must first become familiar with in order to be able to treat them optimally. This article gives an overview of the most important innovations in the last 10 years in the field of systemic therapy in breast cancer and also shows the most important side effects and their management.

The American Society of Breast Surgeons classification system for oncoplastic breast conserving surgery independently predicts the risk of delayed wound healing.

INTRODUCTION: Oncoplastic breast conserving surgery (OBCS) aims to provide safe and satisfying surgery for breast cancer patients. The American Society of Breast Surgeons (ASBrS) classification system is based on volumetric displacement cut-offs (level I for <20% of breast volume; level II for 20-50%). It aims to facilitate communication among treating physicians and patients. Here, we investigate whether the extent of OBCS as classified by ASBrS independently predicts postoperative complications. MATERIALS AND METHODS: This retrospective analysis of a prospectively maintained database included patients with stage I-III breast cancer who underwent OBCS between 03/2011 and 12/2020 at a Swiss university hospital. Outcomes included short-term (≤30 days) complications and chronic (>30 days) pain after surgery. Multivariate logistic regression models were used to identify independent predictors. RESULTS: In total, 439 patients were included, 314 (71.5%) received ASBrS level I surgery, and 125 (28.5%) underwent ASBrS level II surgery. ASBrS level II was found to be an independent predictor of delayed wound healing (odds ratio [OR] 9.75, 95% confidence intervals (CI) 2.96-32.10). However, ASBrS level did not predict chronic postoperative pain (incidence rate ratio [IRR] 1.20, 95%CI 0.85-1.70), as opposed to age (IRR 1.19, 95%CI 1.11-1.27 per 5 years decrease), and weight disorders (underweight [BMI <18.5] vs. normal weight [BMI 18.5 < 25]: IRR 4.02, 95%CI 1.70-9.54; obese [BMI ≥30] vs. normal weight: IRR 2.07, 95%CI 1.37-3.13). CONCLUSION: ASBrS level II surgery predicted delayed wound healing, warranting close clinical follow-up and prompt treatment to avoid delays in adjuvant therapy.

The Lucerne Toolbox 2 to optimise axillary management for early breast cancer: a multidisciplinary expert consensus.

Clinical axillary lymph node management in early breast cancer has evolved from being merely an aspect of surgical management and now includes the entire multidisciplinary team. The second edition of the "Lucerne Toolbox", a multidisciplinary consortium of European cancer societies and patient representatives, addresses the challenges of clinical axillary lymph node management, from diagnosis to local therapy of the axilla. Five working packages were developed, following the patients' journey and addressing specific clinical scenarios. Panellists voted on 72 statements, reaching consensus (agreement of 75% or more) in 52.8%, majority (51%-74% agreement) in 43.1%, and no decision in 4.2%. Based on the votes, targeted imaging and standardized pathology of lymph nodes should be a prerequisite to planning local and systemic therapy, axillary lymph node dissection can be replaced by sentinel lymph node biopsy ( ± targeted approaches) in a majority of scenarios; and positive patient outcomes should be driven by both low recurrence risks and low rates of lymphoedema.

How pollen tubes fight for food: the impact of sucrose carriers and invertases of Arabidopsis thaliana on pollen development and pollen tube growth.

Pollen tubes of higher plants grow very rapidly until they reach the ovules to fertilize the female gametes. This growth process is energy demanding, however, the nutrition strategies of pollen are largely unexplored. Here, we studied the function of sucrose transporters and invertases during pollen germination and pollen tube growth. RT-PCR analyses, reporter lines and knockout mutants were used to study gene expression and protein function in pollen. The genome of Arabidopsis thaliana contains eight genes that encode functional sucrose/H+ symporters. Apart from AtSUC2, which is companion cell specific, all other AtSUC genes are expressed in pollen tubes. AtSUC1 is present in developing pollen and seems to be the most important sucrose transporter during the fertilization process. Pollen of an Atsuc1 knockout plant contain less sucrose and have defects in pollen germination and pollen tube growth. The loss of other sucrose carriers affects neither pollen germination nor pollen tube growth. A multiple knockout line Atsuc1Atsuc3Atsuc8Atsuc9 shows a phenotype that is comparable to the Atsuc1 mutant line. Loss of AtSUC1 can`t be complemented by AtSUC9, suggesting a special function of AtSUC1. Besides sucrose carriers, pollen tubes also synthesize monosaccharide carriers of the AtSTP family as well as invertases. We could show that AtcwINV2 and AtcwINV4 are expressed in pollen, AtcwINV1 in the transmitting tissue and AtcwINV5 in the funiculi of the ovary. The vacuolar invertase AtVI2 is also expressed in pollen, and a knockout of AtVI2 leads to a severe reduction in pollen germination. Our data indicate that AtSUC1 mediated sucrose accumulation during late stages of pollen development and cleavage of vacuolar sucrose into monosaccharides is important for the process of pollen germination.

Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer.

Importance: The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive breast cancer (BC) is currently unknown. Objective: To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after neoadjuvant chemotherapy (NACT). Design, Setting, and Participants: This was a prospective, observational, cohort study conducted from August 2018 to June 2022. This was a preplanned study within the phase 3 randomized clinical OPBC-03/TAXIS trial. Included were patients with confirmed cN-positive BC from 44 private, public, and academic breast centers in 6 European countries. After NACT, residual nodal disease was mandatory, and a minimum follow-up of 2 months was required. Exposures: All patients underwent tailored axillary surgery (TAS) followed by ALND or axillary radiotherapy (ART) according to TAXIS randomization. TAS removed suspicious palpable and sentinel nodes, whereas imaging-guidance was optional. Systemic therapy recommendations were at the discretion of the local investigators. Results: A total of 500 patients (median [IQR] age, 57 [48-69] years; 487 female [97.4%]) were included in the study. In the upfront surgery setting, 296 of 335 patients (88.4%) had hormone receptor (HR)-positive and Erb-B2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-negative disease: 145 (49.0%) underwent ART, and 151 (51.0%) underwent ALND. The median (IQR) number of removed positive lymph nodes without ALND was 3 (1-4) nodes compared with 4 (2-9) nodes with ALND. There was no association of ALND with the proportion of patients undergoing adjuvant chemotherapy (81 of 145 [55.9%] vs 91 of 151 [60.3%]; adjusted odds ratio [aOR], 0.72; 95% CI, 0.19-2.67) and type of systemic therapy. Of 151 patients with NACT, 74 (51.0%) underwent ART, and 77 (49.0%) underwent ALND. The ratio of removed to positive nodes was a median (IQR) of 4 (3-7) nodes to 2 (1-3) nodes and 15 (12-19) nodes to 2 (1-5) nodes in the ART and ALND groups, respectively. There was no observed association of ALND with the proportion of patients undergoing postneoadjuvant systemic therapy (57 of 74 [77.0%] vs 55 of 77 [71.4%]; aOR, 0.86; 95% CI, 0.43-1.70), type of postneoadjuvant chemotherapy (eg, capecitabine: 10 of 74 [13.5%] vs 10 of 77 [13.0%]; trastuzumab emtansine-DM1: 9 of 74 [12.2%] vs 11 of 77 [14.3%]), or endocrine therapy (eg, aromatase inhibitors: 41 of 74 [55.4%] vs 36 of 77 [46.8%]; tamoxifen: 8 of 74 [10.8%] vs 6 of 77 [7.8%]). Conclusion: Results of this cohort study suggest that patients without ALND were significantly understaged. However, ALND did not inform systemic therapy recommendations.

Cylindroma of the breast with CYLD gene mutation: a case report and review of the literature.

BACKGROUND: Cylindroma of the breast is a rare benign neoplasm. Since its first description in 2001, 20 cases have been reported in the literature. METHODS AND RESULTS: We report another case of this rare tumor in a 60-year-old woman with demonstration of the underlying molecular alteration. Histologically, the tumor showed the typical "jigsaw" pattern of a dual population of cells with a triple-negative phenotype. The pathognomonic mutation of the CYLD gene mutation was detected by whole exome sequencing. Cylindromas show morphological overlap with the solid-basaloid variant of adenoid cystic carcinoma, which renders this differential diagnosis difficult. However, distinction of these two lesions is of outmost importance, since cylindromas, in contrast to solid-basaloid variant of adenoid cystic carcinoma, behave in an entirely benign fashion. CONCLUSIONS: Careful evaluation of morphological features such as mitotic figures and cellular atypia is crucial in the diagnostic work-up of triple-negative breast lesions. It is important to keep cylindroma in mind as a pitfall and possible differential diagnosis for the solid-basaloid variant of adenoid cystic carcinoma. Molecular detection of CYLD gene mutation is helpful in cases with ambiguous histology. With this case report, we aim to contribute to a better understanding of mammary cylindroma and facilitate the diagnosis of this rare entity.

Use of sentinel lymph node biopsy in elderly patients with breast cancer - 10-year experience from a Swiss university hospital.

BACKGROUND: The Choosing Wisely initiative recommended the omission of routine sentinel lymph node biopsy (SLNB) in patients ≥ 70 years of age, with clinically node-negative, early stage, hormone receptor (HR) positive and human epidermal growth factor receptor 2 (Her2) negative breast cancer in August 2016. Here, we assess the adherence to this recommendation in a Swiss university hospital. METHODS: We conducted a retrospective single center cohort study from a prospectively maintained database. Patients ≥ 18 years of age with node-negative breast cancer were treated between 05/2011 and 03/2022. The primary outcome was the percentage of patients in the Choosing Wisely target group who underwent SLNB before and after the initiative went live. Statistical significance was tested using chi-squared test for categorical and Wilcoxon rank-sum tests for continuous variables. RESULTS: In total, 586 patients met the inclusion criteria with a median follow-up of 2.7 years. Of these, 163 were ≥ 70 years of age and 79 were eligible for treatment according to the Choosing Wisely recommendations. There was a trend toward a higher rate of SLNB (92.7% vs. 75.0%, p = 0.07) after the Choosing Wisely recommendations were published. In patients ≥ 70 years with invasive disease, fewer received adjuvant radiotherapy after omission of SLNB (6.2% vs. 64.0%, p < 0.001), without differences concerning adjuvant systemic therapy. Both short-term and long-term complication rates after SLNB were low, without differences between elderly patients and those < 70 years. CONCLUSIONS: Choosing Wisely recommendations did not result in a decreased use of SLNB in the elderly at a Swiss university hospital.

Uncertainties and controversies in axillary management of patients with breast cancer.

The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 250 breast surgeons, patient advocates and radiation oncologists from 60 countries. Subsequently, a global virtual consensus panel considered available data, ongoing studies and resource utilization. It agreed that research should no longer be prioritized for standardization of axillary imaging, de-escalation of axillary surgery in node-positive cancer and risk evaluation of modern surgery and radiotherapy. Instead, expert consensus recommendations for clinical practice should be based on current evidence and updated once results from ongoing studies become available. Research on de-escalation of radiotherapy and identification of the most relevant endpoints in axillary management should encompass a meta-analysis to identify knowledge gaps, followed by a Delphi process to prioritize and a consensus conference to refine recommendations for specific trial designs. Finally, treatment of residual nodal disease after surgery was recommended to be assessed in a prospective register.

The Schottky barrier transistor in emerging electronic devices.

This paper explores how the Schottky barrier (SB) transistor is used in a variety of applications and material systems. A discussion of SB formation, current transport processes, and an overview of modeling are first considered. Three discussions follow, which detail the role of SB transistors in high performance, ubiquitous and cryogenic electronics. For high performance computing, the SB typically needs to be minimized to achieve optimal performance and we explore the methods adopted in carbon nanotube technology and two-dimensional electronics. On the contrary for ubiquitous electronics, the SB can be used advantageously in source-gated transistors and reconfigurable field-effect transistors (FETs) for sensors, neuromorphic hardware and security applications. Similarly, judicious use of an SB can be an asset for applications involving Josephson junction FETs.

Tailored axillary surgery - A novel concept for clinically node positive breast cancer.

Axillary surgery in patients with breast cancer has been a history of de-escalation; however, surgery for clinically node-positive breast cancer remained at the dogmatic level of axillary lymph node dissection (ALND). In these patients, currently the only way to avoid ALND is neoadjuvant systemic treatment (NST) with nodal pathologic complete response (pCR) as diagnosed by selective lymph node removal. However, pCR rates are highly dependent on tumor biology, with luminal tumors being most present yet showing the lowest pCR rates. Therefore, the TAXIS trial is investigating whether in clinically node-positive patients, either with residual disease after NST or in the upfront surgical setting, ALND can be safely omitted. All patients undergo tailored axillary surgery (TAS), which includes removal of the biopsied and clipped node, the sentinel lymph nodes as well as all palpably suspicious nodes, turning a clinically positive axilla into a clinically negative. Feasibility of TAS was recently confirmed in the first pre-specified TAXIS substudy. TAS is followed by axillary radiotherapy to treat any remaining nodal disease. Disease-free survival is the primary endpoint of this non-inferiority trial, and morbidity as well as quality of life are the main secondary endpoints, with ALND being known for having a relevant negative impact on both. Currently, 663 of 1500 patients were randomized; accrual completion is projected for 2025. The TAXIS trial stands out in including clinically node-positive patients in both the neoadjuvant and upfront surgery setting, thereby investigating surgical de-escalation at the far-end of the risk spectrum of patients with breast cancer.