Publications by authors named "Simone Muenst"

Article Synopsis
  • The study investigates the role of BRCA promoter methylation in triple-negative breast cancer (TNBC), emphasizing its potential as an alternative to rare somatic BRCA mutations, particularly in relation to the effectiveness of PARP inhibitors.
  • Researchers analyzed BRCA promoter methylation in breast cancer metastases using advanced methylation profiling and tested tumor organoids derived from these tumors for their response to PARP inhibitors.
  • The findings suggest that while BRCA promoter hypermethylation is rare in metastatic breast cancer, it is preserved in xenograft models and may serve as a valuable indicator for targeted PARP inhibitor therapy.
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25 to 50% of patients suffering from colorectal cancer develop liver metastases. The incidence of regional lymph node (LN) metastases within the liver is up to 14%. The need for perihilar lymph node dissection (LND) is still a controversial topic in patients with colorectal liver metastases (CRLM).

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Article Synopsis
  • The incidence of hepatocellular carcinoma (HCC) is rising in the western world, and this study compares complications and survival rates between two liver resection types: anatomic (ALR) and non-anatomic (NALR).
  • The research involved 298 patients treated at specialized centers in Switzerland and Germany from 2009 to 2020 and indicated that ALR had fewer post-operative complications compared to NALR.
  • Despite the differences in complications, there were no significant variations in recurrence-free survival (RFS) and overall survival (OS) rates between the two resection types, and cirrhosis did not affect these outcomes.
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Background: The removal of common bile duct stones by endoscopic retrograde cholangiopancreatography (ERCP) shows excellent results with low complication rates and is therefore considered a gold standard. However, in case of stones non-removable by ERCP, surgical extraction is needed. The surgical approach is still controversial and clinical guidelines are missing.

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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.

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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.

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Purpose: The aim of this study was to evaluate clinical practice heterogeneity in use of neoadjuvant systemic therapy (NST) for patients with clinically node-positive breast cancer in Europe.

Methods: The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614) to include the first 500 randomized patients with confirmed nodal disease at the time of surgery.

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The heterogeneous group of B3 lesions in the breast harbors lesions with different malignant potential and progression risk. As several studies about B3 lesions have been published since the last Consensus in 2018, the 3rd International Consensus Conference discussed the six most relevant B3 lesions (atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), radial scar (RS), papillary lesions (PL) without atypia, and phyllodes tumors (PT)) and made recommendations for diagnostic and therapeutic approaches. Following a presentation of current data of each B3 lesion, the international and interdisciplinary panel of 33 specialists and key opinion leaders voted on the recommendations for further management after core-needle biopsy (CNB) and vacuum-assisted biopsy (VAB).

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Interplay between non-cancerous cells (immune, fibroblasts, mesenchymal stromal cells (MSC), and endothelial cells (EC)) has been identified as vital in driving tumor progression. As studying such interactions in vivo is challenging, ex vivo systems that can recapitulate in vivo scenarios can aid in unraveling the factors impacting tumorigenesis and metastasis. Using the synthetic tumor microenvironment mimics (STEMs)-a spheroid system composed of breast cancer cells (BCC) with defined human MSC and EC fractions, here we show that EC organization into vascular structures is BC phenotype dependent, and independent of ERα expression in epithelial cancer cells, and involves MSC-mediated Notch1 signaling.

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Background: Assessment of programmed death protein-ligand 1 (PD-L1) in triple-negative breast cancer (TNBC) has entered daily practice to identify patients eligible for treatment with immune checkpoint inhibitors. However, different antibodies and different cut-offs for PD-L1 positivity are used, and the interchangeability of these methods is not clear. The aim of our study was to analyze whether different PD-L1 antibodies can be used interchangeably to identify TNBC patients as PD-L1 positive.

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Background: Ovarian cancer (OC) is the fifth most common malignant female cancer with a high mortality, mainly because of aggressive high-grade serous carcinomas (HGSOC), but also due to absence of specific early symptoms and effective detection strategies. The CXCL12-CXCR4 axis is considered to have a prognostic impact and to serve as potential therapeutic target. Therefore we investigated the role of pCXCR4 and CXCR4 expression of the tumor cells and of tumor infiltrating immune cells (TIC) in high-grade serous OC and their association with the recurrence-free (RFS) and overall survival (OS).

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Fibroepithelial lesions (FL) of the breast, in particular, phyllodes tumors (PT) and fibroadenomas, pose a significant diagnostic challenge. There are no generally accepted criteria that distinguish benign, borderline, malignant PT and fibroadenomas. Combined genome-wide DNA methylation and copy number variant (CNV) profiling is an emerging strategy to classify tumors.

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Unlabelled: Blood-borne metastasis of breast cancer involves a series of tightly regulated sequential steps, including the growth of a primary tumor lesion, intravasation of circulating tumor cells (CTC), and adaptation in various distant metastatic sites. The genes orchestrating each of these steps are poorly understood in physiologically relevant contexts, owing to the rarity of experimental models that faithfully recapitulate the biology, growth kinetics, and tropism of human breast cancer. Here, we conducted an in vivo loss-of-function CRISPR screen in newly derived CTC xenografts, unique in their ability to spontaneously mirror the human disease, and identified specific genetic dependencies for each step of the metastatic process.

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Background: Percutaneous cholecystostomy (PC) is a treatment option for acute cholecystitis (AC) in cases where cholecystectomy (CCY) is not feasible due to limited health conditions. The use of PC remains questionable. The aim was to retrospectively analyse the outcome of patients after PC.

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Aim: We developed tailored axillary surgery (TAS) to reduce the axillary tumor volume in patients with clinically node-positive breast cancer to the point where radiotherapy can control it. The aim of this study was to quantify the extent of tumor load reduction achieved by TAS.

Methods: International multicenter prospective study embedded in a randomized trial.

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Introduction: The aim of this study was to assess the feasibility of cell-free DNA (cfDNA) extraction and circulating tumor DNA sequencing in 30-year-old serum samples.

Materials And Methods: We evaluated serum samples from 52 patients with breast cancer, which were collected between 1983 and 1991, with correlating clinicopathologic data. cfDNA was extracted by using the QIAamp Circulating Nucleic Acid Extraction Kit (Qiagen).

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Tall cell carcinoma with reversed polarity (TCCRP) is a rare breast carcinoma with low malignant potential, initially named "breast tumor resembling the tall cell variant of papillary thyroid carcinoma", which has recently been recognized as a separate entity in the 5th edition of the WHO (World Health Organization) classification of breast tumors. Since the first report of this entity in 2003, more than 40 cases have been reported in the literature. Here, we report another case of this rare tumor in a 60-year-old woman.

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Estrogen receptor (ERα) is central in driving the development of hormone-dependent breast cancers. A major challenge in treating these cancers is to understand and overcome endocrine resistance. The Megakaryoblastic Leukemia 1 (MKL1, MRTFA) protein is a master regulator of actin dynamic and cellular motile functions, whose nuclear translocation favors epithelial-mesenchymal transition.

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Article Synopsis
  • Single-cell analyses of breast cancer tumors reveal significant heterogeneity and complexity, which current histological methods do not adequately capture.
  • By using imaging mass cytometry to assess 35 biomarkers, researchers created 720 detailed images from 352 patients, allowing for a deep analysis of tumor and stromal cell characteristics.
  • The findings identified unique subgroups of breast cancer that correlate with different clinical outcomes, suggesting that single-cell analysis could enhance personalized diagnosis and treatment strategies.
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Purpose: Ovarian carcinoma (OC) is the most lethal female genital cancer. After a primary curative surgical approach followed by chemotherapy, a fraction of the patients recur with chemoresistant disease. Data indicate a favorable therapeutic effect of tumor-infiltrating neutrophils (TIN) in OC.

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Triple-negative breast cancer (TNBC) represents about 10-20% of all invasive breast cancers and is associated with a poor prognosis. The nectin cell adhesion protein 4 (Nectin-4) is a junction protein involved in the formation and maintenance of cell junctions. Nectin-4 has previously shown to be expressed in about 60% of TNBC as well as in TNBC metastases, but to be absent in normal breast tissue, which makes it a potential specific target for TNBC therapy.

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Fibrocystic changes are associated with an increased risk of breast cancer. Genetic alterations have been found in fibrocystic changes with or without epithelial changes, suggesting that critical oncogenic events are occurring at an early stage. We investigated a unique collective of 17 breast cancer patients who, prior to the diagnosis of invasive breast cancer, underwent open surgical biopsy showing fibrocystic changes of the breast.

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Purpose: Myeloperoxidase (MPO) is an enzyme secreted by neutrophil granulocytes as a result of phagocytosis during inflammation. In colorectal cancer, tumour infiltration by MPO expressing cells has been shown to be independently associated with a favourable prognosis. In this study, we explored the role of MPO-positive cell infiltration and its prognostic significance in invasive breast cancer.

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CD40 triggering may result in antitumor effects of potentially high clinical relevance. To gain insights important for patient selection and to identify adequate targeting techniques, we investigated CD40 expression in human cancer tissues and generated a replication-incompetent recombinant vaccinia virus expressing CD40 ligand (rVV40L). Its effects were explored and upon direct CD40 targeting on malignant cells or macrophage activation.

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Breast cancer is a heterogeneous disease. Tumor cells and associated healthy cells form ecosystems that determine disease progression and response to therapy. To characterize features of breast cancer ecosystems and their associations with clinical data, we analyzed 144 human breast tumor and 50 non-tumor tissue samples using mass cytometry.

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