Carsten Denkert

Carsten Denkert
Philipps University of Marburg | PUM · Institute of Pathology

Professor

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803
Publications
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Publications

Publications (803)
Article
Background Up to 40% of patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer develop brain metastases (BMs). Understanding of clinical features of these patients with HER2-positive breast cancer and BMs is vital. Patients and methods A total of 2948 patients from the Brain Metastases in Breast Cancer regi...
Poster
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Introduction: One hallmark characteristic of small intestinal neuroendocrine neoplasms (SI-NENs) is the development of mesenteric fibrosis (MF). However, this is only the case in ∼ 50 % of patients while responsible molecular mechanisms remain unknown. MF can cause intestinal obstruction and ischemia inducing increased levels of suffering and often...
Article
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Background Risk assessment on the molecular level is important in predictive pathology to determine the risk of metastatic disease for ERpos, HER2neg breast cancer. The gene expression test EndoPredict (EP) was trained and validated for prediction of a 10-year risk of distant recurrence to support therapy decisions regarding endocrine therapy alone...
Preprint
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Background: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is an option in advanced peritoneal sarcomatosis. Nevertheless, CRS and HIPEC are not successful in all patients. An enhancement of HIPEC using photodynamic therapy might be beneficial. Therefore, a combination of the photosensitizer Hyperi...
Article
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Estrogen receptor-positive breast cancer is a highly prevalent but heterogeneous disease among women. Advanced molecular stratification is required to enable individually most efficient treatments based on relevant prognostic and predictive biomarkers. First objective of this study was the hypothesis driven discovery of biomarkers involved in tumor...
Article
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Background: Special AT-rich sequence-binding protein 2 (SATB2) has emerged as an alternative immunohistochemical marker to CDX2 for colorectal differentiation. However, the distribution and prognostic relevance of SATB2 expression in colorectal carcinoma (CRC) have to be further elucidated. Methods: SATB2 expression was analysed in 1039 CRCs and...
Article
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Background Current clinical guidelines suggest that breast cancers with low hormone receptor expression (LowHR) in 1–10% of tumor cells should be regarded as hormone receptor positive. However, clinical data show that these patients have worse outcome compared to patients with hormone receptor expression above 10%. We performed DNA methylation prof...
Article
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In the BrighTNess trial, carboplatin added to neoadjuvant chemotherapy (NAC) was associated with increased pathologic complete response (pCR) rates in patients with stage II/III triple-negative breast cancer (TNBC). In this matched cohort study, cases with a germline BRCA1/2 mutation (gBRCA; n = 75) were matched 1:2 with non-gBRCA controls ( n = 15...
Article
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The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed dea...
Article
Background GeparOcto demonstrated that pathological complete response (pCR) of intense dose-dense epirubicin, paclitaxel and cyclophosphamide (iddEPC) was comparable to weekly paclitaxel/non-pegylated liposomal doxorubicin (plus carboplatin (PM(Cb) in triple-negative breast cancer [TNBC]) in high-risk early breast cancer (BC). Here, we report time-...
Article
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Background: Colorectal mixed adenoneuroendocrine carcinomas (MANECs) are clinically highly aggressive neoplasms. MANECs are composed of variable adenocarcinoma components combined with morphologically distinct neuroendocrine carcinoma components, which are confirmed by synaptophysin immunohistochemistry, the gold standard marker of a neuroendocrin...
Article
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Increased stiffness of solid tissues has long been recognized as a diagnostic feature of several pathologies, most notably malignant diseases. In fact, it is now well established that elevated tissue rigidity enhances disease progression and aggressiveness and is associated with a poor prognosis in patients as documented, for instance, for lung fib...
Article
Background The GAIN-2 trial was designed to identify a superior intense dose-dense (idd) strategy for high-risk patients with early breast cancer. Here, we report an interim analysis, at which the predefined futility boundary was crossed. Patients and methods GAIN-2 was an open-label, randomised, multicentre phase III trial. Two thousand eight hun...
Article
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Patients with advanced triple-negative breast cancer (TNBC) benefit from treatment with atezolizumab, provided that the tumor contains ≥1% of PD-L1/SP142-positive immune cells. Numbers of tumor-infiltrating lymphocytes (TILs) vary strongly according to the anatomic localization of TNBC metastases. We investigated inter-pathologist agreement in the...
Article
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Estrogen receptor (ER), progesterone receptor (PgR), Ki-67, and HER2 immunohistochemistry (IHC) together with HER2 in situ hybridization (ISH) are utilized to classify invasive breast cancer (IBC) into predictive molecular subtypes. As IHC evaluation may be hampered by analytical errors, gene expression assays could offer a reliable alternative. In...
Article
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Correction to: TGFB-induced factor homeobox 1 (TGIF) expression in breast cancer
Article
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[This corrects the article DOI: 10.1371/journal.pone.0238021.].
Article
Background Current genetic and genomic tests measuring homologous recombination deficiency (HRD) show limited predictive value. This study compares the performance of an immunohistology-based RAD51 test with genetic/genomic tests to identify patients with HRD primary triple-negative breast cancer (TNBC) and evaluates its accuracy to select patients...
Article
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Background Breast cancer (BC) is the most frequent female cancer and preferentially metastasizes to bone. The transcription factor TGFB-induced factor homeobox 1 (TGIF) is involved in bone metabolism. However, it is not yet known whether TGIF is associated with BC bone metastasis or patient outcome and thus of potential interest. Methods TGIF expr...
Article
Background Guideline recommendations for treatment of breast cancer with low hormone receptor (HR) expression (1-9%) are ambiguous and several studies showed more similarities with HR negative tumors than with HR strongly positive tumors (≥10%). We used a population-based 15-year cohort to compare patient characteristics and outcome of HR low posit...
Article
Importance Patients with breast cancer remain at risk of relapse after adjuvant therapy. Celecoxib has shown antitumor effects in preclinical models of human breast cancer, but clinical evidence is lacking. Objective To evaluate the role of celecoxib as an addition to conventional therapy for women with ERBB2 (formerly HER2)–negative primary breas...
Article
Background Young women receiving chemotherapy for early breast cancer (EBC) have a high probability for ovarian failure, defined by chemotherapy-induced amenorrhea (CIA) as a surrogate. CIA is insufficiently reliable and reproducible. We analysed chemotherapy-induced ovarian failure (CIOF) by assessing hormone parameters, CIA, and antral follicle c...
Article
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Background Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy has been established as a novel treatment approach for peritoneal sarcomatosis. Despite promising clinical reports, there is still a lack of knowledge regarding optimal drug usage and local effects. Therefore, we intended to establish a murine animal mode...
Article
Background The development of anti-HER2 antibody–drug conjugates opens new therapeutic options for patients with breast cancer, including patients with low expression of HER2. To characterise this new breast cancer subtype, we have compared the clinical and molecular characteristics of HER2-low-positive and HER2-zero breast cancer, including respon...
Article
In 2014, we described a method to quantify percentage of tumor-infiltrating lymphocytes (TILs) on haematoxylin and eosin (H&E) stained slides of breast cancer samples using light microscopy that could be performed easily by pathologists with no extra stains. The aim of detailing the method was to facilitate independent research groups replicating o...
Article
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Background The Mucin-family protein, MUC1, impacts on carcinogenesis and tumor invasion. We evaluated the impact of MUC1 expression on outcome in a cohort of 158 patients with resected pancreatic ductal adenocarcinomas (PDAC) in the CONKO-001 study (adjuvant gemcitabine [gem] vs. observation [obs]).Methods The percentage of MUC1-positive tumor cell...
Article
Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with superior survival. This association is strongest in triple-negative breast cancer (TNBC). The CPS + EG system, based on pre-treatment clinical (CS) and post-treatment pathological stage (PS), oestrogen-receptor status (E) and grade (G), leads...
Article
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Zusammenfassung Hintergrund Seit über 30 Jahren findet regelmäßig die internationale St.-Gallen(SG)-Konsensuskonferenz zur Behandlung des primären Mammakarzinoms (SG-BCC) statt. Bei diesem Konsens handelt es sich um ein Meinungsbild von Experten unterschiedlicher Länder und Fachdisziplinen. Rationale Vor diesem Hintergrund werden die Abstimmungse...
Article
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Zusammenfassung Die diesjährige 17. St.-Gallen(SG)-Konsensus-Konferenz zur Behandlung von Patientinnen mit frühem Mammakarzinom (SG-BCC) stand unter dem Motto „Customizing local and systemic therapies for women with early breast cancer“ und fokussierte auf die Herausforderung, die Behandlung des frühen Mammakarzinoms zielgerichteter auf die individ...
Conference Paper
Abstract für die 40. Jahrestagung der Deutschen Gesellschaft für Senologie 2021 Outcome von Mammakarzinomen mit schwach positiven Hormonrezeptoren: Eine bevölkerungsbezogene Analyse eines 15-Jahres-Kollektivs S. Schrodi, M. Braun, A. Andrulat, N. Harbeck, S. Mahner, M. Kiechle, E. Klein, A. Schnelzer, C. Schindlbeck, I. Bauerfeind, G. Schubert-Fr...
Article
519 Background: About one third of patients with hormone-receptor-positive (HR+), HER2‐ primary breast cancer with residual invasive disease after neoadjuvant chemotherapy will relapse despite adjuvant endocrine therapy. Therapeutic inhibition of cyclin-dependent kinase 4 and 6 (CDK 4/6) by palbociclib combined with endocrine therapy demonstrated h...
Article
TPS602 Background: Women with triple-negative breast cancer (TNBC) having residual disease after neoadjuvant chemotherapy (NACT) as well as HR-positive/HER2-negative breast cancer (BC) with a CPS (clinical and post treatment pathological stage) +EG (estrogen receptor status and grade) score ≥ 3 or score 2 and nodal involvement after NACT (ypN+) are...
Article
506 Background: The GeparNuevo trial investigated the addition of durvalumab, an anti-PD-L1 checkpoint inhibitor (CPI), to standard neoadjuvant chemotherapy (NACT) in patients with early TNBC. Durvalumab increased the pathological complete response (pCR) rate particularly in patients treated with durvalumab alone before start of chemotherapy (Loibl...
Article
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This yearʼs 17th St. Gallen (SG) Consensus Conference on the Treatment of Patients with Early Breast Cancer (SG-BCC) with the title “Customizing local and systemic therapies for women with early breast cancer” focused on the challenge of targeting the treatment of early breast cancer more specifically to the individual disease situation of each pat...
Article
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The prognosis of early breast cancer (BC) relies on cell autonomous and immune parameters. The impact of the intestinal microbiome on clinical outcome has not yet been evaluated. Shotgun metagenomics was used to determine the composition of the fecal microbiota in 121 specimens from 76 early BC patients, 45 of whom were paired before and after chem...
Article
Aim To evaluate HER2-negative breast cancer (BC) with a low hormone receptor (HR) expression, with regard to pathological complete response (pCR) and survival, in comparison to triple-negative BC (TNBC) and strong HR-positive BC. Methods We compared negative [oestrogen (ER) and progesterone receptor (PR) <1%], low-positive (ER and/or PR 1–9%) and...
Article
Background Improved understanding of molecular biology has increasingly raised the question of whether entity-independent tumor agnostic therapy can be used.Objectives Is agnostic and non-entity-specific tumor therapy currently required, with particular reference to advanced breast cancer?Materials and methodsWe define the tumor agnostic approach a...
Article
The development of the WHO classification of tumors of the breast is driven by new knowledge from research whose translation into daily practice is considered clinically relevant. The fifth edition represents an update of the fourth edition and essentially follows the previously known systematics. The histologic features of the lesions continue to...
Article
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Recent advances in cancer research and diagnostics largely rely on new developments in microscopic or molecular profiling techniques, offering high levels of detail with respect to either spatial or molecular features, but usually not both. Here, we present an explainable machine-learning approach for the integrated profiling of morphological, mole...
Article
PURPOSE About one third of patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer who have residual invasive disease after neoadjuvant chemotherapy (NACT) will relapse. Thus, additional therapy is needed. Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor demonstrating efficacy in the metast...
Article
Breast cancer is still the most common cancer worldwide. But the way breast cancer is viewed has changed drastically since its molecular hallmarks were extensively characterised, now including immunohistochemical markers (eg, ER, PR, HER2 [ERBB2], and proliferation marker protein Ki-67 [MKI67]), genomic markers (eg, BRCA1, BRCA2, and PIK3CA), and i...
Article
Importance: Adding carboplatin to standard neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) likely benefits a subset of patients; however, determinants of benefit are poorly understood. Objective: To define the association of molecular subtype, tumor proliferation, and immunophenotype with benefit of carboplatin added to NA...
Article
Full-text available
Several scores have been developed in order to estimate the prognosis of patients with brain metastases (BM) by objective criteria. The aim of this analysis was to validate all three published graded-prognostic-assessment (GPA)-scores in a subcohort of 882 breast cancer (BC) patients with BM in the Brain Metastases in the German Breast Cancer (BMBC...
Article
Purpose: We evaluated mRNA signatures to predict response to neoadjuvant PD-L1 inhibition in combination with chemotherapy in early triple-negative breast cancer. Experimental design: Targeted mRNA sequencing of 2559 transcripts was performed in FFPE samples from 162 patients of the GeparNuevo trial. We focused on validation of four predefined g...
Conference Paper
Background: About one third of patients with hormone-receptor-positive (HR+), HER2‐ primary breast cancer with residual invasive disease after neoadjuvant chemotherapy will relapse despite adjuvant endocrine therapy. The risk of relapse can be assessed more accurately using the CPS‐EG scoring system (Mittendorf et al. JCO 2011). Therapeutic inhibit...
Conference Paper
Background: Risk assessment on molecular level is becoming more common in modern pathology to determine the recurrence risk for patients diagnosed with estrogen receptor positive (ER+), HER2 negative (HER2-) breast cancer (BC). The gene expression test EndoPredict (EP) was trained and validated to predict a 10-year risk of distant recurrence to sup...
Preprint
Full-text available
Constitutively active estrogen receptor-α (ER/ ESR1 ) mutations have been identified in approximately one third of ER+ metastatic breast cancer. Although these mutations are known mediators of endocrine resistance, their potential role in promoting metastatic disease has not yet been mechanistically addressed. In this study, we show the presence of...
Article
Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Preprint
Full-text available
Background: Breast cancer (BC) is the most frequent female cancer its which preferentially metastasizes to bone. Mechanisms of bone tropism are poorly understood, however, the transcription factor TGFB-induced factor homeobox 1 (TGIF) is involved in bone metabolism and thus of potential interest. Methods: TGIF expression was analyzed by immunohisto...