Publications by authors named "Martina Vetter"

Breast cancer (BC) is a leading cause of death worldwide, particularly also among African woman. In order to better stratify patients for the most effective (immuno-) therapy, an in depth characterization of the immune status of BC patients is required. In this study, a cohort of 65 Ethiopian patients with primary BC underwent immune profiling by multicolor flow cytometry on peripheral blood samples collected prior to surgery and to any other therapy.

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Background: The clinical management of breast cancer (BC) is mainly based on the assessment of receptor expression by tumour cells. However, there is still an unmet need for novel biomarkers important for prognosis and therapy. The tumour immune microenvironment (TIME) is thought to play a key role in prognosis and therapy selection, therefore this study aimed to describe the TIME in Ethiopian BC patients.

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Purpose: Survival rates of breast cancer (BC) patients are particularly low in rural regions in sub-Saharan Africa (SSA) which is due to limited access to therapy. In recent years, gene expression profiling (GEP) of BC showed a strong prognostic value in patients with local tumour surgery and (neo)adjuvant treatment. The aim of this study was to evaluate the impact of intrinsic subtypes on survival of patients in rural Ethiopia without any (neo)adjuvant therapy.

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Purpose: Systemic therapy plays a major part in the cure of patients with early breast cancer (eBC). However, personalized treatment concepts are required to avoid potentially harmful overtreatment. Biomarkers are pivotal for individualized therapy.

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GRB2 is an adaptor protein of HER2 (and several other tyrosine kinases), which we identified as a novel BECN1 (Beclin 1) interacting partner. GRB2 co-immunoprecipitated with BECN1 in several breast cancer cell lines and regulates autophagy through a mechanism involving the modulation of the class III PI3Kinase VPS34 activity. In ovo studies in a CAM (Chicken Chorioallantoic Membrane) model indicated that GRB2 knockdown, as well as overexpression of GRB2 loss-of-function mutants (Y52A and S86A-R88A) compromised tumor growth.

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Article Synopsis
  • Breast cancer is the leading cause of cancer deaths among women in Ethiopia, particularly affecting those of African ancestry, but the reasons for this high mortality rate are not fully understood.
  • Recent research in high-income countries has shown that imbalances in microbial communities (microbial dysbiosis) may play a key role in breast cancer development and outcomes, yet this has not been explored in Ethiopian women.
  • This study identified 14 distinct microbial genera in breast tumor tissues compared to adjacent normal tissues, linking certain bacteria to aggressive cancer types and advanced disease stages in Ethiopian women, marking a significant first step in understanding the relationship between microbiota and breast cancer outcomes.
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The low overall survival rates of patients with breast cancer in sub-Saharan Africa (SSA) are driven by regionally differing tumor biology, advanced tumor stages at diagnosis, and limited access to therapy. However, it is not known whether regional differences in the composition of the tumor microenvironment (TME) exist and affect patients' prognosis. In this international, multicentre cohort study, 1,237 formalin-fixed, paraffin-embedded breast cancer samples, including samples of the "African Breast Cancer-Disparities in Outcomes (ABC-DO) Study," were analyzed.

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Background: In node-negative breast cancer (NNBC), a high risk of recurrence is determined by clinico-pathological or tumor-biological assessment. Taxanes may improve adjuvant chemotherapy.

Methods: NNBC 3-Europe, the first randomized phase-3 trial in node-negative breast cancer (BC) with tumor-biological risk assessment, recruited 4146 node-negative breast cancer patients from 2002 to 2009 in 153 centers.

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Tumour-infiltrating lymphocytes (TILs) are considered to have prognostic and predictive value for patients with early breast cancer. We examined 1166 breast cancer patients from a prospective, multicentre cohort (Prognostic Assessment in Routine Application (PiA), = 1270, NCT01592825) following recommendations from the International TILs Working Group. TIL quantification was performed using predefined groups and as a continuous variable in 10% increments.

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Purpose: The recent development of multi-gene assays for gene expression profiling has contributed significantly to the understanding of the clinically and biologically heterogeneous breast cancer (BC) disease. PAM50 is one of these assays used to stratify BC patients and individualize treatment. The present study was conducted to characterize PAM50-based intrinsic subtypes among Ethiopian BC patients.

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Purpose: Phosphatidylinositide-3-kinase (PI3K) regulates proliferation and apoptosis; somatic PIK3CA-mutations may activate these processes. Aim of this study was to determine the prevalence of PIK3CA-mutations in a cohort of early stage breast cancer patients and the association to the course of disease.

Patients And Methods: From an unselected cohort of 1270 breast cancer patients (PiA, Prognostic Assessment in routine application, NCT01592825) 1123 tumours were tested for the three PIK3CA hotspot-mutations H1047R, E545K, and E542K by qPCR.

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In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna® in a prospective multicentric study. In 119/142 cases, Prosigna® molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping.

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In breast cancer, the promising efficacy of farnesyltransferase inhibitors (FTIs) in preclinical studies is in contrast to only limited effects in clinical Phase II-III trials. The objective of this study was to explore the clinical relevance of farnesyltransferase β-subunit () single nucleotide promoter polymorphisms (-173 6G > 5G (rs3215788), -609 G > C (rs11623866) and -179 T > A (rs192403314)) in early breast cancer. genotyping was performed by pyrosequencing in 797 patients from a prospective multicentre observational PiA trial (NCT01592825).

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Introduction: Triple-negative breast cancer (TNBC) is considered the most aggressive type of breast cancer (BC) with limited options for therapy. TNBC is a heterogeneous disease and tumors have been classified into TNBC subtypes using gene expression profiling to distinguish basal-like 1, basal-like 2, immunomodulatory, mesenchymal, mesenchymal stem-like, luminal androgen receptor (LAR), and one nonclassifiable group (called unstable).

Objectives: The aim of this study was to verify the clinical relevance of molecular subtyping of TNBCs to improve the individual indication of systemic therapy.

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Introduction: Endocrine therapy for breast cancer (BC) patients is highly underutilized in rural Ethiopia and other African countries.

Objective: This study aims to assess the feasibility of and adherence to tamoxifen therapy in rural Ethiopia.

Methods: We ascertained the hormone receptor (HR) status in 101 women diagnosed with BC from January 2010 to December 2015 and who had surgery in Aira Hospital, in rural Ethiopia.

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HER3 is highly expressed in luminal breast cancer subtypes. Its activation by NRG1 promotes activation of AKT and ERK1/2, contributing to tumour progression and therapy resistance. HER3-targeting agents that block this activation, are currently under phase 1/2 clinical studies, and although they have shown favorable tolerability, their activity as a single agent has proven to be limited.

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Uncontrolled proliferation and altered metabolic reprogramming are hallmarks of cancer. Active glycolysis and glutaminolysis are characteristic features of these hallmarks and required for tumorigenesis. A fine balance between cancer metabolism and autophagy is a prerequisite of homeostasis within cancer cells.

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Epithelial-to-mesenchymal transition (EMT) is a hallmark of aggressive, mesenchymal-like high-grade serous ovarian carcinoma (HGSOC). The SRC kinase is a key driver of cancer-associated EMT promoting adherens junction (AJ) disassembly by phosphorylation-driven internalization and degradation of AJ proteins. Here, we show that the IGF2 mRNA-binding protein 1 (IGF2BP1) is up-regulated in mesenchymal-like HGSOC and promotes SRC activation by a previously unknown protein-ligand-induced, but RNA-independent mechanism.

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The caspase 8 variants CASP8 -652 6N InsDel and Asp302His have previously been identified to promote survival of T-lymphocytes and to indicate reduced breast cancer susceptibility. Besides some preliminary findings, prognostic relevance of these polymorphisms in patients with existing breast cancer has not been investigated. Considering an immunomodulatory role of these polymorphisms, we genotyped 785 early breast cancer patients and correlated caspase 8 variants with disease-free survival (DFS) and the presence of tumor infiltrating lymphocytes (TILs).

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Background: Genetic factors play a substantial role in breast cancer etiology. Genes encoding proteins that have key functions in the DNA damage response, such as p53 and its inhibitors MDM2 and MDMX, are most likely candidates to harbor allelic variants that influence breast cancer susceptibility. The aim of our study was to comprehensively analyze the impact of SNPs in the , , and genes in conjunction with mutational status regarding the onset and progression of breast cancer.

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Breast cancer patients at high risk for recurrence are treated with anthracycline-based chemotherapy, but not all patients do equally benefit from such a regimen. To further improve therapy decision-making, biomarkers predicting outcome are of high unmet medical need. The percent DNA methylation ratio (PMR) of the promoter gene coding for the Paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time polymerase chain reaction (PCR) test.

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Motivation: Several gene expression-based risk scores and subtype classifiers for breast cancer were developed to distinguish high- and low-risk patients. Evaluating the performance of these classifiers helps to decide which classifiers should be used in clinical practice for personal therapeutic recommendations. So far, studies that compared multiple classifiers in large independent patient cohorts mostly used microarray measurements.

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Purpose: The objective of this study was to compare tumor characteristics, biomarkers, and surrogate subtypes of breast cancer between Sudanese and German women.

Methods: Tumor characteristics and immunohistochemistry markers (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor 2 [HER2]) were collected from the routine assessment of consecutive patients with invasive breast cancer diagnosed from 2010 to 2015 (Gezira University Pathology Laboratory, Gezira, Sudan) and from 1999 to 2013 (Breast Centre, Martin-Luther-University, Halle, Germany).

Results: A total of 2,492 patients (German [n = 1,932] and Sudanese [n = 560]) were included.

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Breast cancer is the most common cancer in women worldwide. The tumor microenvironment contributes to tumor progression by inducing cell dissemination from the primary tumor and metastasis. TGFβ signaling is involved in breast cancer progression and is specifically elevated during metastatic transformation in aggressive breast cancer.

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