JNK ‐dependent gene regulatory circuitry governs mesenchymal fate

The epithelial to mesenchymal transition (EMT) is a biological process in which cells lose cell-cell contacts and become motile. EMT is used during development, for example, in triggering neural crest migration, and in cancer metastasis. Despite progress, the dynamics of JNK signaling, its role in genomewide transcriptional reprogramming, and involved downstream effectors during EMT remain largely unknown. Here, we show that JNK is not required for initiation, but progression of phenotypic changes associated with EMT. Such dependency resulted from JNK-driven transcriptional reprogramming of critical EMT genes and involved changes in their chromatin state. Furthermore, we identified eight no…

Feasibility of an induced metabolic bioluminescence imaging technique in ovarian cancer: Results of a pilot study.

e17093Background: The precise determination of energy metabolites is challenged by the heterogeneity of their distribution, their rapid changes after surgical resection and the architectural comple...

Nationwide Analysis on Surgical Staging Procedures and Systemic Treatment for Patients With Endometrial Cancer in Germany

ObjectiveIn 2009 and 2006, the Arbeitsgemeinschaft Gynäkologische Onkologie evaluated therapeutic approaches for endometrial carcinoma (EC) in Germany.Methods and MaterialsA questionnaire was developed and sent to 775 German gynecologic departments in 2009 (500 in 2006). The results of the questionnaires were compared with each other and with the recommendations of the Arbeitsgemeinschaft Gynäkologische Onkologie’s guideline. Subgroup analyses were performed, dividing the participating centers into small and large centers and into centers with less and more experience with EC.ResultsResponses were available in 33.3% in 2009 and 35.8% in 2006. Comparing 2009 with 2006, it became apparent tha…

Cerebral metastases of an endometrial stromal sarcoma: report of the first case.

Endometrial stromal sarcomas (ESSs) of the uterus are rare gynecological malignancies. Common locations of distant metastases are vagina, vulva, lung, mediastinum, abdomen, bones and ovaries.We present the case of a 69-year-old woman with a Federation of Gynecology and Obstetrics (FIGO) IIb (classification 2009) ESS of the uterus of high-grade malignancy. Initially, a hysterectomy Piver II and total colpectomy were performed, followed by pelvic field irradiation. 8 months later, the patient suffered seizures and hemiparesis. A computed tomography (CT) scan revealed cerebral metastases, and irradiation of the brain was initiated. After completion of the staging examinations, additional metas…

Prognostic Significance of Focal Adhesion Kinase in Node-Negative Breast Cancer.

<b><i>Background:</i></b> Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that plays an important role as a mediator of cell migration, invasion, proliferation and survival. Conflicting results for the prognostic role of FAK in breast cancer (BC) prompted us to determine its impact. <b><i>Methods:</i></b> Patients with node-negative BC entered this retrospective study. FAK expression was determined by immunohistochemistry (n = 335). The prognostic impact of FAK was examined with Cox regression analyses and Kaplan-Meier estimation in the whole cohort as well as in different molecular subtypes. <b><i>Results:</i>&l…

Therapie des fortgeschrittenen hormonrezeptor(HR)-positiven HER2-negativen Mammakarzinoms

ZusammenfassungDer Artikel gibt einen Überblick über die aktuellen Therapieoptionen des metastasierten hormonrezeptorpositiven und HER2-negativen Mammakarzinoms. Im Fokus stehen Kombinationstherapien z. B. mit CDK4/6-Inhibition im Vergleich zu rein endokrin basierten Therapien in Prä- und Postmenopause mit Darlegung der neuesten Studienergebnisse. Die Hinzunahme eines CDK4/6-Inhibitors zu einer endokrin basierten Therapie mit Aromataseinhibitor oder Fulvestrant führt zu einer deutlichen Verbesserung des progressionsfreien Überlebens und ist vorteilhaft unabhängig davon, ob es sich um Palbociclib, Ribociclib oder Abemaciclib handelt. Der daher besondere klinische Stellenwert der Inhibition c…

Abstract PS10-16: Real-world efficacy of ribociclib + aromatase inhibitor/fulvestrant, or endocrine monotherapy, or chemotherapy as first-line treatment in women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: Third interim analysis from the RIBANNA study

Abstract Background: In MONALEESA-3 and MONALEESA-7 trials, ribociclib (RIB, a selective CDK4/6 inhibitor) in combination with endocrine therapy (aromatase inhibitor [AI] or fulvestrant [FUL]) demonstrated a significant prolongation of overall survival among patients with breast cancer (BC), regardless of menopausal status and treatment-line. In the premenopausal or perimenopausal women, RIB + AI/FUL should be combined with a luteinizing hormone-releasing hormone agonist. The real-world evidence for the effectiveness, safety, and tolerability of RIB + AI/FUL in the routine clinical practice is needed to support the use of this combination. Methods: RIBANNA is a prospective, non-intervention…

Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

Summary Background Antiangiogenic therapy has known activity in ovarian cancer. The investigator-initiated randomised phase 2 TRIAS trial assessed the multi-kinase inhibitor sorafenib combined with topotecan and continued as maintenance therapy for platinum-resistant or platinum-refractory ovarian cancer. Methods We did a multicentre, double-blind, placebo-controlled, randomised, phase 2 trial at 20 sites in Germany. Patients (≥18 years) with platinum-resistant ovarian cancer previously treated with two or fewer chemotherapy lines for recurrent disease were stratified (first vs later relapse) in block sizes of four and randomly assigned (1:1) using a web-generated response system to topotec…

The impact of treatment for genital cancer on quality of life and body image—results of a prospective longitudinal 10-year study

Abstract Objective . To evaluate the impact of treatment for genital cancer on quality of life and body image to determine patients' therapy-related needs for quality improvement of medical care before and after surgery. Methods . We started to evaluate women with cervical cancer planned for pelvic exenteration in 1993 and integrated women planned for a Wertheim–Meigs surgery in 1995 before surgery, 4 and 12 months after surgery. Thanks to funding since 1999, more than 400 patients with a diagnosis of genital ( n = 185) or breast ( n = 217) cancer participated in this prospective study until July 2003. In this paper, we will focus on n = 129 women with cervical cancer. The assessment protoc…

253 PFS of elderly ovarian cancer patients might be predicted by G-8 geriatric screening tool – results of a retrospective cohort study

Introduction/Background* The aim of this study was to evaluate the impact of the preoperative global health status on the prognosis of patients with ovarian cancer (OC) older than 60 years, who received cytoreductive surgery. Methodology G-8 geriatric screening tool (G-8 score), Lee Schonberg prognostic index, Eastern Cooperative Oncology Group (ECOG) performance status and Charlson Comorbidity Index (CCI) were determined retrospectively in a consecutive cohort of elderly patients with OC. Univariate and multivariate Cox regression analyses and Kaplan-Meier method were performed to analyze the impact of the preoperative global health status on survival. Result(s)* 116 patients entered the s…

Gene Expression Analyses in Early Breast Carcinoma — Quo Vadis?

AbstractIn order to establish whether adjuvant therapy should be administered in patients with breast carcinoma, it is decisive to have as precise as possible an assessment of the risk of recurrence. In this context, gene expression — and thus gene expression signatures as well — have become a focus of attention as prognostic factors. For practical application, it is important to be able to analyze gene expression signatures in formalin-fixed, paraffin-embedded tumor tissue. Careful analytic and clinical validations and a high level of evidence (LoE) are required in order to avoid imprecise risk classification and thus potential overtreatment or undertreatment of the patients. Among the com…

Optimizing taxane use in MBC in the emerging era of targeted chemotherapy.

The first-generation taxanes, conventional paclitaxel and docetaxel, are established treatment options for adjuvant and metastatic breast cancer (MBC). However, these agents have limitations, including primary/secondary resistance and harsh toxicities. The introduction of paclitaxel albumin represents a significant advance in taxane therapy as the first of a new generation of taxanes. This agent utilizes albumin pathways to achieve enhanced and targeted drug delivery to the tumour. The lack of solvent also means that it is well tolerated, despite the lack of premedications. Paclitaxel albumin is licensed in the United States and Europe as ≥2nd-line therapy in MBC (260mg/m(2) once every thre…

Synchronous Ovarian and Endometrial Cancer—an International Multicenter Case-Control Study

ObjectivesThis study aimed to compare the prognosis of patients with synchronous endometrial and ovarian cancer (SEOC) to matched controls with either endometrial cancer (EC) or ovarian cancer (OC).MethodsA retrospective case-control study including all patients with SEOC who had been treated at 5 European tertiary gynecologic oncology centers between 1996 and 2011 and patients with either EC or OC matched for age, International Federation of Gynecology and Obstetrics (FIGO) stage, histology, year of diagnosis, and Eastern Cooperative Oncology Group performance score.ResultsThe study cohort comprised 77, 132, and 126 patients with SEOC, EC, and OC, respectively. The patient characteristics …

Comparison of tear protein levels in breast cancer patients and healthy controls using a de novo proteomic approach

Noninvasive biomarkers are urgently needed for early detection of breast cancer since the risk of recurrence, morbidity and mortality are closely related to disease stage at the time of primary surgery. In the past decade, many proteomics-based approaches were developed that utilize the protein profiling of human body fluids or identification of putative biomarkers to obtain more knowledge on the effects of cancer emergence and progression. Herein, we report on an analysis of proteins in the tear fluid from breast carcinoma patients and healthy women using a de novo proteomic approach and 25 mixed samples from each group. This study included 25 patients with primary invasive breast carcinom…

News from ASCO 2017

Reduced numbers of IL-7 receptor (CD127) expressing immune cells and IL-7-signaling defects in peripheral blood from patients with breast cancer

Interleukin-7-receptor-signaling plays a pivotal role in T-cell development and maintenance of T-cell memory. We studied IL-7Ralpha (CD127) expression in PBMCs obtained from patients with breast cancer and examined IL-7 receptor-mediated downstream effects defined by STAT5 phosphorylation (p-STAT5). Reduced numbers of IL-7Ralpha-positive cells were identified in CD4+ T-cells as well as in a CD8+ T-cell subset defined by CD8alpha/alpha homodimer expression in patients with breast cancer. PBMCs obtained from healthy donors (n = 19) and from patients with breast cancer (n = 19) exhibited constitutive p-STAT5 expression in the range of 0-6.4% in CD4+ T-cells and 0-4% in CD8+ T-cells. Stimulatio…

Abstract CT020: MERIT: introducing individualized cancer vaccines for the treatment of TNBC - a phase I trial

Abstract The majority of metastatic cancers remain incurable since the current methods of treatment often fail to target the heterogeneous nature of each individual patient's tumor. Personalized approaches targeting each individual patient's tumor may therefore bring significant improvements. The Mutanome Engineered RNA Immuno-Therapy (MERIT) consortium will clinically validate a pioneering RNA-based immunotherapy concept for the treatment of triple negative breast cancer (TNBC) by targeting shared tumor antigens and individual neo-antigens in TNBC patients. MERIT combines two personalized treatment concepts: (i) treatment with vaccines containing “off-the-shelf” mRNAs selected from a pre-s…

Chemotherapy in early breast cancer: when, how and which one?

The efficacy of chemotherapy depends on the level of risk of the individual patient. Because of this, careful estimation of the risk level is mandatory. In addition to well-established clinicopathological factors, validated gene expression signatures might be useful in selected patients if all other criteria are inconclusive for therapeutic decision-making. If indicated, chemotherapy can be used either after surgery (adjuvant) or before surgery (neoadjuvant). Both approaches lead to comparable long-term survival. The neoadjuvant setting offers the additional opportunity for elaborate translational studies to develop and validate predictive biomarkers and to discover mechanisms of resistance…

Preoperative assessment of breast cancer: sonography versus MR imaging.

The purposes of our study were to compare the diagnostic value of whole-breast sonography and MR imaging as adjunctive techniques to mammography and to determine whether MR imaging should be used routinely in the preoperative assessment of patients with suspected breast cancer.. One hundred four women (age range, 34-84 years; mean age, 60 years) with findings highly suggestive of malignancy in the breast were examined with mammography, sonography, and dynamic MR imaging before undergoing surgery. All visualized suspicious lesions were correlated histologically. The diagnostic relevance of sonographic and MR imaging findings was compared with the diagnostic value of the findings of clinical …

The proteasome inhibitor Bortezomib (Velcade) as potential inhibitor of estrogen receptor-positive breast cancer

Around 70% of breast cancers express the estrogen receptor α (ERα) and depend on estrogen for growth, survival and disease progression. The presence of hormone sensitivity is usually associated with a favorable prognosis. Use of adjuvant anti-endocrine therapy has significantly decreased breast cancer mortality in patients with early-stage disease, and anti-endocrine therapy also plays a central role in the treatment of advanced stages. However a subset of hormone receptor-positive breast cancers do not benefit from anti-endocrine therapy, and nearly all hormone receptor-positive metastatic breast cancers ultimately develop resistance to anti-hormonal therapies. Despite new insights into me…

345 Comparison of cisplatin and mitomycin/5-FU as radiosensitizers in the treatment of vulvar cancer – results of a single institutional cohort study

Introduction/Background* Treatment of vulvar cancer contains surgery if applicable and often primary or neo-/adjuvant chemoradiation. Cisplatin and Mitomycin/5-FU are widely used radiosensitizers in vulvar cancer, although evidence is limited. We retrospectively investigated both radiosensitizers for outcome and toxicity. Methodology We screened the archive for patients treated with chemoradiation for pathologically-confirmed squamous cell cancer of the vulva between 01/2010 – 02/2021 at our institution. The impact of both radiosensitizers on prognosis was compared using Kaplan-Meier method and Cox-Regression analysis. Result(s)* 127 patients with vulvar cancer were screened. 24 patients re…

Dose-Dense Chemotherapy in Metastatic Breast Cancer: Shortening the Time Interval for a Better Therapeutic Index

Despite the advancement of targeted therapies in metastatic breast cancer, chemotherapy is still of pivotal importance. The concept of dose density is known to increase the efficacy of chemotherapy. In metastatic disease, preservation of the quality of life is equally important. Because of this, weekly regimens are a cornerstone in metastatic disease. Taxanes like paclitaxel or nab-paclitaxel as well as antracyclines are often used in palliative treatment. Further advances to increase dose density have led to the concept of daily metronomic schedules with oral chemotherapeutic drugs like cyclophosphamide, capecitabine, or vinorelbine. Metronomic chemotherapy affects tumor angiogenesis and a…

Loss of circadian clock gene expression is associated with tumor progression in breast cancer

Several studies suggest a link between circadian rhythm disturbances and tumorigenesis. However, the association between circadian clock genes and prognosis in breast cancer has not been systematically studied. Therefore, we examined the expression of 17 clock components in tumors from 766 node-negative breast cancer patients that were untreated in both neoadjuvant and adjuvant settings. In addition, their association with metastasis-free survival (MFS) and correlation to clinicopathological parameters were investigated. Aiming to estimate functionality of the clockwork, we studied clock gene expression relationships by correlation analysis. Higher expression of several clock genes (e.g., C…

Mitotic figure counts are significantly overestimated in resection specimens of invasive breast carcinomas.

Several authors have demonstrated an increased number of mitotic figures in breast cancer resection specimen when compared with biopsy material. This has been ascribed to a sampling artifact where biopsies are (i) either too small to allow formal mitotic figure counting or (ii) not necessarily taken form the proliferating tumor periphery. Herein, we propose a different explanation for this phenomenon. Biopsy and resection material of 52 invasive ductal carcinomas was studied. We counted mitotic figures in 10 representative high power fields and quantified MIB-1 immunohistochemistry by visual estimation, counting and image analysis. We found that mitotic figures were elevated by more than th…

Association Between CYP2D6 Polymorphisms and Outcomes Among Women With Early Stage Breast Cancer Treated With Tamoxifen

Context The growth inhibitory effect of tamoxifen, which is used for the treatment of hormone receptor–positive breast cancer, is mediated by its metabolites, 4-hydroxytamoxifen and endoxifen. The formation of active metabolites is catalyzed by the polymorphic cytochrome P450 2D6 (CYP2D6) enzyme. Objective To determine whether CYP2D6 variation is associated with clinical outcomes in women receiving adjuvant tamoxifen. Design, Setting, and Patients Retrospective analysis of German and US cohorts of patients treated with adjuvant tamoxifen for early stage breast cancer. The 1325 patients had diagnoses between 1986 and 2005 of stage I through III breast cancer and were mainly postmenopausal (9…

Prognostic Influence of Pre-Operative C-Reactive Protein in Node-Negative Breast Cancer Patients

The importance of inflammation is increasingly noticed in cancer. The aim of this study was to analyze the prognostic influence of pre-operative serum C-reactive protein (CRP) in a cohort of 148 lymph node-negative breast cancer patients. The prognostic significance of CRP level for disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS) was evaluated using univariate and multivariate Cox regression, also including information on age at diagnosis, tumor size, tumor grade, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, proliferation index (Ki67) and molecular subtype, as well as an assessment of the…

Evaluation of a novel monoclonal antibody against tumor-associated MUC1 for diagnosis and prognosis of breast cancer

There is still a great unmet medical need concerning diagnosis and treatment of breast cancer which could be addressed by utilizing specific molecular targets. Tumor-associated MUC1 is expressed on over 90 % of all breast cancer entities and differs strongly from its physiological form on epithelial cells, therefore presenting a unique target for breast cancer diagnosis and antibody-mediated immune therapy. Utilizing an anti-tumor vaccine based on a synthetically prepared glycopeptide, we generated a monoclonal antibody (mAb) GGSK-1/30, selectively recognizing human tumor-associated MUC1. This antibody targets exclusively tumor-associated MUC1 in the absence of any binding to MUC1 on health…

Targeted Therapies Overcoming Endocrine Resistance in Hormone Receptor-Positive Breast Cancer

Breast cancer is a heterogeneous disease with different molecular subtypes. Most tumours are hormone receptor positive (luminal subtype) with potential endocrine responsiveness. Endocrine therapy is commonly used in these patients. Disease progression caused by endocrine resistance represents a significant challenge in the treatment of breast cancer. To understand the mechanisms of resistance of long-term oestrogen-deprived breast cancer cells, it is important to focus on cross-talk between steroid receptor signalling and other growth factor receptors and intracellular pathways. (Pre-)clinical trials showed that co-targeting these pathways can restore endocrine sensitivity. The focus of the…

German Adjuvant Intergroup Node Positive (GAIN) study: A phase III trial to compare IDD-ETC versus EC-TX in patients with node-positive primary breast cancer—Final efficacy analysis.

1009 Background: Intense dose-dense (idd) epirubicin (E), paclitaxel (T), cyclophosphamide (C) (idd-ETC) resulted in a superior disease-free (DFS) and overall survival (OS) compared to conventional...

237 Selected global health assessment tools significantly predict postoperative clinical outcome in elderly patients with ovarian cancer

Introduction/Background* This study evaluated the impact of the global health status on the rate of postoperative clinical complications in patients with ovarian cancer (OC) older than 60 years. Methodology Selected global health status assessment tools were retrospectively determined in a cohort of OC patients older than 60 years, treated at our institution between 2008 and 2019. The primary outcome was the incidence and type of postoperative clinical complications in accordance with the Veteran Affairs’ National Surgical Quality Improvement Program (NSQIP). Differences in binary and ordinal variables between independent groups were analyzed by the chi-square test. Furthermore, rank correl…

Prevalence of Cardiac Disease in Breast Cancer Patients at Time of Diagnosis Compared to the General Female Population in Germany.

<b><i>Background:</i></b> Advances in oncological therapy have significantly improved breast cancer survival; therefore comorbid conditions are becoming more relevant. We investigated the prevalence of prior cardiovascular diseases and risk factors in patients with breast cancer compared to those in the general female population in Germany. <b><i>Methods:</i></b> The PASSOS heart study is a retrospective multicenter cohort study on cardiac late effects in breast cancer patients treated between 1998 and 2008. We analyzed the frequencies of cardiac diseases and cardiovascular risk factors in patients from this cohort as documented in anesthesia …

Serum proteome profiling of primary breast cancer indicates a specific biomarker profile.

Non-invasive biomarkers for early breast cancer detection are urgently needed, as the risk of recurrent morbidity and mortality is closely related to the stage of the disease at the time of primary surgery. Currently, there are no established clinical biomarkers for breast cancer. Evaluation of protein expression patterns in body fluids using proteomic technologies can be used to discover new biomarkers for the detection of breast cancer. The aim of this study was to identify a biomarker signature identifying primary non-metastatic breast cancer and healthy controls. We screened 91 serum samples including 45 breast cancer patients and 46 healthy women using a proteomic approach. We found 14…

The role of surgery in patients with primary metastatic breast cancer (PMBC) receiving monoclonal antibody treatment.

1097 Background: Apart from the individual palliative need, the beneficial effect of surgically removing the primary tumor in PMBC on long-term outcomes, as suggested by retrospective series and me...

Prognostic Significance of Interferon-γ and Its Signaling Pathway in Early Breast Cancer Depends on the Molecular Subtypes

Interferons are crucial for adaptive immunity and play an important role in the immune landscape of breast cancer. Using microarray-based gene expression analysis, we examined the subtype-specific prognostic significance of interferon-&gamma

Catumaxomab: a bispecific trifunctional antibody.

The trifunctional bispecific monoclonal antibody catumaxomab has two binding specificities directed at epithelial cell adhesion molecule (EpCAM) and the T-cell antigen CD3. With its Fc-fragment, catumaxomab additionally binds accessory cells such as dendritic cells, macrophages and natural killer cells. The trifunctional approach thus leads to unrestricted but specific killing of epithelial tumor cells by major histocompatibility complex without the need for preactivation or external costimulation. The tumor-associated antigen EpCAM is strongly expressed in carcinomas of various origins including colon, rectum, ovarian, gastric, esophagus, lung, pancreas, breast and head and neck. Expressio…

CD8+CD45RA+CD27-CD28-T-cell subset in PBL of cervical cancer patients representing CD8+T-cells being able to recognize cervical cancer associated antigens provided by HPV 16 E7

Objective In response to antigenic stimulation, naive MHC-class I restricted and antigen-specific CD8+CD45RA+CD28+T-cells undergo clonal expansion and differentiate into CD8+CD45RO+ memory T-cells. Upon re- encounter with the nominal antigen, CD45RO+ T-cells are able to convert to CD8+CD45RA+CD28-T-cells displaying potent immune effector functions, including TNF-alpha production. This T-cell subpopulation constitutes a minor population in healthy individuals. In the present study we are currently evaluating whether this particular T-cell subset in PBL represents CD8+T-cells which may be able to recognize cervical cancer associated antigens provided by HPV 16 E7. Material and methods Flow-cy…

A randomized, open-label, multicentre, phase IV study evaluating palbociclib plus endocrine treatment versus a chemotherapy based treatment strategy in patients with hormone receptor positive/HER2-negative metastatic breast cancer in a real world setting.

TPS1115 Background: Although endocrine based therapy is recommended as first-line treatment in metastatic breast cancer (MBC) in patients with an HER2-/HR+ tumour up to 50% of the patients receive chemotherapy. Palbociclib (P) a CDK4/6 inhibitor improves PFS by 42% in endocrine sensitive and resistant HER2-/HR+ MBC when added to an endocrine therapy (ET). Patients included in clinical trials are often criticised not to be representative for real world breast cancer patients. Methods: Patients with first-line HER2-/HR+ MBC who are candidate for mono-chemotherapy will be eligible to be randomised 1:1 to receive either P plus ET per label or mono-chemotherapy per investigator´s choice with or…

Trastuzumab treatment in patients with advanced breast cancer (ABC) confined to locoregional and skeletal sites: Results from a large noninterventional study.

640 Background: In a prospective observation study routine trastuzumab (T) treatment in HER2+ ABC was evaluated in a total of 1,687 patients (pts) since 2001. This large number allows the subgroup analysis of patients with the involvement of specific sites. Methods: Information on extent of advanced disease was available in 1,674 pts (99%) with HER2 overexpressing ABC. Pts were either pre-treated (39%) or naïve to palliative chemotherapy (CT). The following subgroups and their characteristics were analysed: I: locally ABC only; II: bone metastases allowing for concomitant local tumour; III: other. Results: Locally advanced lesions were found to be the sole BC manifestation in 145 pts (8.7%…

The EndoPredict Gene-Expression Assay in Clinical Practice - Performance and Impact on Clinical Decisions

The validated EndoPredict assay is a novel tool to predict the risk of metastases of patients with estrogen receptor positive, HER2 negative breast cancer treated with endocrine therapy alone. It has been designed to integrate genomic and clinical information and includes clinico-pathological factors such as tumor size and nodal status. The test is feasible in a decentral setting in molecular pathology laboratories. In this project, we investigated the performance of this test in clinical practice, and performed a retrospective evaluation of its impact on treatment decisions in breast cancer. During one year, EndoPredict assays from 167 patients could be successfully performed. For retrospe…

Metronomic Chemotherapy for Metastatic Breast Cancer.

<b><i>Background:</i></b> As disease control and quality of life play a leading role in metastatic breast cancer (MBC), metronomic chemotherapy (MCT) is gaining popularity alongside conventional chemotherapy (CCT) and targeted therapies. <b><i>Summary:</i></b> MCT, defined as continuous administration of low-dose chemotherapeutic agents, is accepted as a therapy that exerts its effects via immunomodulation, anti-angiogenesis and direct cytotoxic effects. Oral administration of MCT is safe, easy to handle, and allows for flexible drug dosing. Dose accumulations associated with non-tolerable side effects are rare, so the medication can be admini…

AGO Recommendations for the Surgical Therapy of the Axilla After Neoadjuvant Chemotherapy: 2021 Update

Geburtshilfe und Frauenheilkunde 81(10), 1112-1120 (2021). doi:10.1055/a-1499-8431

Prognostic significance of the chemokine CXCL13 in node-negative breast cancer

615 Background: The chemokine CXCL13 is chemotactic for B cells. We examined the prognostic significance of CXCL13 mRNA expression in node-negative breast cancer. Methods: Microarray based gene-expression data for CXCL13 (205242_at) were analysed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n=824). A meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance of CXCL13 on metastasis-free survival (MFS) was examined in the whole cohort and in different molecular subtypes (ER+/HER2-, ER-/HER2-, HER2+). Independent prognostic relevance was a…

External training load and the effects on training response following three different training sessions in young elite beach volleyball players

Purpose The interaction between external training load (ETL) and players internal response in beach volleyball is currently poor investigated. Using single parameters (e.g. jump volume) described in indoor settings is questionable due to specific load characteristics like sandy ground and reduced number of players. The aim of this work is to analyze ETL and the effects on training response in different beach volleyball training settings. Methods This study was conducted with 7 youth elite athletes (age: 18.9 ± 1.3 years, height: 185.2 ± 7 cm, body mass: 75.9 ± 10.4 kg, 2 males/5 females). Training sessions were classified into three categories with (A) high session jump volume (SJV) and low…

Brain Metastases in Breast Cancer Network Germany (BMBC, GBG 79): Treatment patterns and clinical outcome of more than 1000 patients with brain metastases from breast cancer.

2070Background: In order to improve knowledge about treatment and outcome of breast cancer patients with brain metastases (BM) we initiated the registry Brain Metastases in Breast Cancer Network Ge...

246 Survival of elderly patients with endometrial cancer – predicted by preoperative G-8 geriatric screening tool

Introduction/Background* We evaluated the prognostic impact of various global health assessment tools in accordance to conventional prognostic factors in patients with endometrial cancer (EC) older than 60 years. Methodology G-8 geriatric screening tool (G-8 geriatric score), Lee Schonberg prognostic index (Lee-Index), Charlson Comorbidity Index (CCI) and American Society of Anesthesiologists (ASA-PS) – Physical Status System were retrospectively determined in a consecutive cohort of elderly patients with EC. Univariate and multivariate Cox regression analyses and Kaplan-Meier method were performed to determine the impact of the global health assessment tools on progression free survival (P…

Ki-67 as an independent prognostic factor in an unselected cohort of patients with ovarian cancer: results of an explorative, retrospective study.

The identification of prognostic markers has clinical implications in epithelial ovarian carcinoma (EOC). Here, we studied markers for proliferation (Ki-67), endocrine regulation [progesterone receptor (PR), estrogen receptor (ER)], and invasion [urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1)]. All patients with available follow-up information and EOC tissue, who were treated at our institution between 1997 and 2004, were enrolled in the present study. Expression of Ki-67, PR and ER was determined by immunohistochemical analyses. uPA and PAI-1 antigen levels were determined using enzyme‑linked immunosorbent assays. One hundred and eight patients enter…

Analysis of everolimus starting dose as prognostic marker in HR+ mBC patients treated with everolimus (EVE) + exemestane (EXE): Results of the 3rd interim analysis of the non-interventional trial BRAWO.

1061 Background: BRAWO is a German non-interventional study, which enrolled more than 2400 patients (pts) with advanced/metastatic, hormone-receptor-positive and HER2-negative breast cancer treated with EVE and EXE. Main objectives are a) the impact of physical activity on efficacy and quality of life, b) prophylaxis and management of stomatitis in clinical routine, and c) the sequence of therapy when EVE is used in daily clinical practice. Methods: In this update on the results of the 3rd interim analysis (data cut-off 18-Oct-2016) we analyzed under real world conditions the first 1.078 patients followed up until disease progression for their progression-free survival (PFS) events. A two-…

Abstract P2-05-04: Gene expression associated with poor prognosis of young TNBC patients

Abstract Background: Among TNBC patients those of very young age (<40 years) display a significantly worse prognosis (Liedtke et al. 2013 Breast Cancer Res Treat). We verified this result in 1161 TNBC samples with full Affymetrix gene expression data of which 845 patients had both detailed age and follow up information. Materials and Methods: We split the full sample set into a finding cohort of 394 TNBC and a validation cohort of 767 TNBC encompassing 309 and 536 samples, respectively, with both age and follow up data. We then used significance analysis of microarrays (SAM) in the finding cohort to look for genes whose expression is associated with young age (<40 years). Iden…

Prognostic significance of Focal Adhesion Kinase (FAK) in node-negative breast cancer.

552 Background: Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase playing an important role as a key mediator for signal transduction. We examined the subtype specific prognostic signifi...

Overall survival results from the randomized phase II study of palbociclib (P) in combination with letrozole (L) vs letrozole alone for frontline treatment of ER+/HER2– advanced breast cancer (PALOMA-1; TRIO-18).

1001 Background: Preclinical data identified a synergistic role for P and hormone blockade in blocking growth of ER+ breast cancer (BC) cell lines. PALOMA-1 was an open-label phase II trial comparing progression-free survival (PFS) in patients (pts) with advanced ER+/HER2– BC treated with P+L or L alone. Median PFS increased with addition of P to L to 20.2 mos (vs 10.2 mos with L alone; HR = 0.488), with an acceptable safety profile, leading to accelerated approval by the US FDA. These results were confirmed in the phase 3 PALOMA-2 trial. At the time of the final PFS analysis, overall survival (OS) data were immature with only 61 events in both arms and a median follow-up of < 30 mos wi…

ERBB2 Induces an Antiapoptotic Expression Pattern of Bcl-2 Family Members in Node-Negative Breast Cancer

AbstractPurpose: Members of the Bcl-2 family act as master regulators of mitochondrial homeostasis and apoptosis. We analyzed whether ERBB2 influences the prognosis of breast cancer by influencing the proapoptotic versus antiapoptotic balance of Bcl-2 family members.Experimental Design: ERBB2-regulated Bcl-2 family members were identified by inducible expression of ERBB2 in MCF-7 breast cancer cells and by correlation analysis with ERBB2 expression in breast carcinomas. The prognostic relevance of ERBB2-regulated and all additional Bcl-2 family members was determined in 782 patients with untreated node-negative breast cancer. The biological relevance of ERBB2-induced inhibition of apoptosis…

Topotecan (T) ± sorafenib (S) in platinum-resistant ovarian cancer (PROC): A double-blind placebo-controlled randomized NOGGO–AGO intergroup Trial—TRIAS.

5522Background: Sorafenib (S), a multi TK-inhibitor in combination with topotecan (T), a topoisomerase inhibitor showed preclinical synergistic effects in ovarian cancer but critical toxicity. To a...

Palbociclib - from Bench to Bedside and Beyond.

Endocrine therapy is the cornerstone in the treatment of hormone receptor-positive breast cancer. During the last decades, much has been learned about the subtle regulation of the cell cycle. In this tightly regulated network, cyclin-dependent kinases (CDKs) play a pivotal role. Especially CDK4/6 is the key regulator of the G1-S transition. Realizing its importance, specific inhibitors of CDK4/6 were developed. The drug most advanced in clinical development in this class is palbociclib (PD 0332991). This review highlights preclinical data and brings into focus early clinical trials that led to an accelerated approval by the US Food and Drug Administration (FDA) as first-line treatment in co…

Neo-/adjuvant phase III trial to compare intense dose-dense (idd) treatment with EnPC to tailored dose-dense (dt) therapy with dtEC-dtD for patients with high-risk early breast cancer: Results on pathological complete response (pCR) for patients treated within the neoadjuvant setting.

568Background: GAIN-2 compares the effectiveness and safety of a predefined idd regimen (EnPC) vs. a dd regimen with modification of single doses depending on individual hematological and non-hemat...

Geriatric assessment and biomarkers in patients with metastatic breast cancer receiving first-line mono-chemotherapy: Results from the randomized phase III PELICAN trial.

Abstract Objectives To determine predictive/prognostic factors for patients with metastatic breast cancer (MBC) receiving first-line monochemotherapy using biomarker analysis and geriatric assessment (GA). Materials and Methods Karnofsky Performance Status (KPS) and GA as clinical parameters, and prognostic inflammatory and nutritional index (PINI), and Glasgow prognostic score (GPS) as biomarkers were analyzed for association with clinical outcome within the randomized phase III PEg-LIposomal Doxorubicin vs. CApecitabin iN MBC (PELICAN) trial of first-line pegylated liposomal doxorubicin (PLD) or capecitabine. Results Of 210 patients, 38% were > 65 years old. GA (n = 152) classified 74% as…

Carcinoma of the neovagina: case report and review of the literature.

Abstract Background. Carcinoma of the vagina is a rare disease, and it is even more rare in the neovagina. Nevertheless, it has been well described. The aim of this report was to analyze the reported cases and to add observations concerning a risk profile for this rare occurrence of carcinoma. Case report. The 29-year-old patient's history included congenital absence of vagina as a result of Rokitansky–Kuster syndrome. In 1987, when the patient was 17 years old, a neovagina was constructed by dissection between the bladder and the rectum, according to the Warthon method, and the apex of the neovagina was covered with Dura-mater. In 1990 the patient underwent radiation treatment with brachyt…

Node-Negative Breast Cancer: Which Patients Should Be Treated?

Adjuvant systemic therapy has led to markedly improved outcome in early-stage breast cancer. However, the absolute gains from chemotherapy might be modest in node-negative patients. Adjuvant chemotherapy is the only option for triple-negative breast cancer patients and should be used with trastuzumab in HER2-positive patients. Considering the large group of patients with some degree of endocrine responsiveness, adding chemotherapy according to risk is an option. At present, we guide our therapeutic decisions using clinicopathologic risk classifications like the St. Gallen risk category or Adjuvant! online. A downside of these risk estimations is a low specificity and consequently the risk f…

Systems Biology, Bioinformatics and Medicine Approaches to Cancer Progression Outcomes

Because of the complexity of carcinogenesis and tumour development, it is critical to understand the underlying organizing principles. In this chapter a possible approach is illustrated, starting with a description of breast cancer prognosis as a function of three powerful biological motifs derived from gene expression profiling. A proliferation metagene describing the transition from slow to fast proliferation leads to the most dramatic aggravation of prognosis. A second immune cell metagene represents an opponent of tumour evolution, whereby only fast-proliferating tumours that are not recognized and eliminated by immune cells can progress. In the absence of endocrine treatment, a third m…

Control of dataset bias in combined Affymetrix cohorts of triple negative breast cancer

AbstractHeterogenous subtypes of breast cancer need to be analyzed separately. Pooling of datasets can provide reasonable sample sizes but dataset bias is an important concern. We assembled a combined dataset of 579 Affymetrix microarrays from triple negative breast cancer (TNBC) in Gene Expression Omnibus (GEO) series GSE31519. We developed a method for selecting comparable datasets and to control for the amount of dataset bias of individual probesets.

Functional characterization of circulating tumor cells (CTCs) from metastatic ER+/HER2− breast cancer reveals dependence on HER2 and FOXM1 for endocrine therapy resistance and tumor cell survival: Implications for treatment of ER+/HER2− breast cancer

Simple Summary Acquired endocrine resistance and late recurrence in patients with ER+/HER2− breast cancer are complex and not fully understood. Here, we evaluated mechanisms of acquired resistance in circulating tumor cells (CTCs) from an ER+/HER2− breast cancer patient who initially responded but later progressed under endocrine treatment. We found a switch from ERα-dependent to HER2-dependent and ERα-independent expression of FOXM1, which may enable disseminated ER+/HER2− cells to re-initiate tumor cell growth and metastasis formation in the presence of endocrine treatment. We found that NFkB signaling sustains HER2 and FOXM1 expression in CTCs in the presence of ERα inhibitors suggesting…

Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy With or Without Carboplatin in Human Epidermal Growth Factor Receptor 2–Positive and Triple-Negative Primary Breast Cancers

Purpose Modulation of immunologic interactions in cancer tissue is a promising therapeutic strategy. To investigate the immunogenicity of human epidermal growth factor receptor 2 (HER2) –positive and triple-negative (TN) breast cancers (BCs), we evaluated tumor-infiltrating lymphocytes (TILs) and immunologically relevant genes in the neoadjuvant GeparSixto trial. Patients and Methods GeparSixto investigated the effect of adding carboplatin (Cb) to an anthracycline-plus-taxane combination (PM) on pathologic complete response (pCR). A total of 580 tumors were evaluated before random assignment for stromal TILs and lymphocyte-predominant BC (LPBC). mRNA expression of immune-activating (CXCL9, …

Subcutaneous trastuzumab therapy for HER2-positive early breast cancer in the routine clinical practice: First interim analysis of the National Non-Interventional Study (NIS) HerSCin.

581Background: In 2013 a subcutaneous (SC) formulation of trastuzumab (T) was approved based on non-inferiority to intravenous (IV) T as proven in the HannaH trial. So far no data from the routine ...

Phase III randomised trial comparing intense dose-dense chemotherapy to tailored dose-dense chemotherapy in high-risk early breast cancer (GAIN-2)

Abstract 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 hundred and eighty seven patients were randomised 1:1 between three courses each of idd epirubicin (E) 150 mg/m2, nab-paclitaxel (nP) 330 mg/m2 and cyclophosphamide (C) 2000 mg/m2 (iddEnPC) versus four cycles of leucocyte nadir-based tailored and dose-dense EC (dtEC) followed by four cycles of tailored and dose-dense docetaxel (dtD) (dtEC-dtD…

Impact of prognostic factors on long-term outcomes in metastatic breast cancer (MBC) patients (pts) receiving bevacizumab (B) plus paclitaxel as first-line cytotoxic treatment.

e12007 Background: B combined with chemotherapy (CT) significantly improves progression-free survival (PFS) and response rate (RR) vs CT alone in the first-line treatment of HER2-negative MBC. In a...

c-met is overexpressed in type I ovarian cancer: Results of an investigative analysis in a cohort of consecutive ovarian cancer patients

The tyrosine kinase c-met alters signaling cascades such as the BRAF-MAPK and PI3K-PKB pathways. These alterations are involved in the carcinogenesis of type I but not type II ovarian cancer (OC). Therefore, the present study investigated the patterns of c-met expression in a cohort of consecutive patients with OC. c-met expression was determined by immunohistochemical analysis. Differences in c-met overexpression among subgroups of established clinicopathological features, including age, histological subtype, tumor stage, histological grading, post-operative tumor burden and completeness of chemotherapy, were determined by χ2 test. Cox regression analyses were performed to determine the pr…

The Impact of Insulin on Low-dose Metronomic Vinorelbine and Mafosfamide in Breast Cancer Cells

Background/aim Breast cancer (BC) may be affected by diabetes and anti-diabetic medication, as well as its therapeutic agents. Low-dose metronomic chemotherapy (LDMC) is an available treatment option in BC. We investigated the impact of insulin on low-dose metronomic vinorelbine and mafosfamide in BC cell lines. Materials and methods Human BC cell lines T-47D, MCF-7, MDA-MB-231, BT-549 and non-tumorigenic breast cell line MCF-10A were exposed to 0.01 μg/ml and 10 μg/ml insulin in combination with low-dose metronomic vinorelbine or mafosfamide. The cell viability was determined after 24-72 hours using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Results Insulin, especi…

Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) - Part 2 with Recommendations for the Therapy of Primary, Recurrent and Advanced Breast Cancer

Geburtshilfe und Frauenheilkunde 78(11), 1056-1088 (2018). doi:10.1055/a-0646-4630

Reduced Breast Tumor Growth after Immunization with a Tumor-Restricted MUC1 Glycopeptide Conjugated to Tetanus Toxoid.

Abstract Preventive vaccination against tumor-associated endogenous antigens is considered to be an attractive strategy for the induction of a curative immune response concomitant with a long-lasting immunologic memory. The mucin MUC1 is a promising tumor antigen, as its tumor-associated form differs from the glycoprotein form expressed on healthy cells. Due to aberrant glycosylation in tumor cells, the specific peptide epitopes in its backbone are accessible and can be bound by antibodies induced by vaccination. Breast cancer patients develop per se only low levels of T cells and antibodies recognizing tumor-associated MUC1, and clinical trials with tumor-associated MUC1 yielded unsatisfac…

Sa.33. Interleukin-7 Receptor (IL-7r) Mediated Signaling Effects in Immune Cells:Novel Readout for ‘Immune Competence’

Immunoglobulin Kappa C Predicts Overall Survival in Node-Negative Breast Cancer

Background: Biomarkers of the immune system are currently not used as prognostic factors in breast cancer. We analyzedthe association of the B cell/plasma cell marker immunoglobulin kappa C (IGKC) and survival of untreated node-negative breast cancer patients.Material and Methods: IGKC expression was evaluated by immunostaining in a cohort of 335 node-negative breast cancer patients with a median follow-up of 152 months. The prognostic significance of IGKC for disease-free survival (DFS) and breast cancer-specific overall survival (OS) was evaluated with Kaplan-Meier survival analysis as well as univariate and multivariate Cox analysis adjusted for age at diagnosis, pT stage, histological g…

Prognostic Impact of Immunoglobulin Kappa C in Breast Cancer Patients Treated with Adjuvant Chemotherapy.

<b><i>Introduction:</i></b> Immunoglobulin κC (IGKC)-positive tumor-infiltrating plasma cells are associated with better prognosis in node-negative breast cancer patients without adjuvant systemic therapy. In the present study we evaluated the prognostic significance of IGKC in breast cancer patients treated with adjuvant chemotherapy ± tamoxifen. <b><i>Methods:</i></b> IGKC expression was immunohistochemically analyzed in 193 breast cancer patients who were treated with adjuvant chemotherapy, either with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) between 1993 and 2001 wit…

Analysis according to prognostic factors in patients (pts) treated with first-line bevacizumab (BEV) combined with paclitaxel (PAC) for HER2-negative metastatic breast cancer (mBC) in a routine oncology practice study.

1077 Background: 1st-line BEV combined with weekly PAC significantly improves progression-free survival (PFS) and response rate (RR) vs PAC alone in HER2-negative mBC, as shown in E2100. We analyzed data from a German routine oncology practice study of 1st-line BEV–PAC according to prognostic factors. Methods: Pts who had received no prior chemotherapy for mBC received BEV–PAC according to the European label. Efficacy and safety were documented for up to 1 y (or until progression, death, or BEV discontinuation if earlier) with additional long-term follow-up. Efficacy was analyzed in clinically important subgroups. Results: Efficacy data were available for 818 pts. The median duration of fo…

Antibody microarray analysis of the serum proteome in primary breast cancer patients

Noninvasive biomarkers are urgently needed for detecting breast cancer as early as possible since the risk of recurrence, morbidity, and mortality is closely related to disease stage at the time of primary surgery. There are currently no such biomarkers in clinical use as a diagnostic tool. Proteomic analysis of protein expression patterns in body fluids has potential for use in identifying biomarkers of breast cancer. The aim of this study was to compare protein expression levels in the sera of primary breast cancer patients and healthy controls. An antibody microarray tool with 23 antibodies immobilized on nitrocellulose slides was used to determine the levels of acute phase proteins, int…

Characteristics and Clinical Outcome of Breast Cancer Patients with Asymptomatic Brain Metastases

Background: Brain metastases (BM) have become a major challenge in patients with metastatic breast cancer. Methods: The aim of this analysis was to characterize patients with asymptomatic BM (n = 580) in the overall cohort of 2589 patients with BM from our Brain Metastases in Breast Cancer Network Germany (BMBC) registry. Results: Compared to symptomatic patients, asymptomatic patients were slightly younger at diagnosis (median age: 55.5 vs. 57.0 years, p = 0.01), had a better performance status at diagnosis (Karnofsky index 80&ndash

Impact of the EndoPredict-clin score on risk stratification in ER-positive, HER2-negative breast cancer after considering clinical guidelines.

542 Background: Many ER-positive, HER2-negative breast cancer patients are treated by adjuvant chemotherapy according to current clinical guidelines. We retrospectively assessed whether the combined gene expression/ clinicopathological EndoPredict-clin (EPclin) score improved the accuracy of risk classification in addition to considering clinical guidelines. Methods: Three clinical breast cancer guidelines (National Comprehensive Cancer Center Network (NCCN), German S3 and St. Gallen 2011), and the EPclin score - assessed by quantitative RT-PCR in formalin-fixed paraffin-embedded tissue - were used to assign risk groups in 1,702 ER-positive, HER2-negative breast cancer patients from two ra…

From High-Throughput Microarray-Based Screening to Clinical Application: The Development of a Second Generation Multigene Test for Breast Cancer Prognosis

Several multigene tests have been developed for breast cancer patients to predict the individual risk of recurrence. Most of the first generation tests rely on proliferation-associated genes and are commonly carried out in central reference laboratories. Here, we describe the development of a second generation multigene assay, the EndoPredict test, a prognostic multigene expression test for estrogen receptor (ER) positive, human epidermal growth factor receptor (HER2) negative (ER+/HER2−) breast cancer patients. The EndoPredict gene signature was initially established in a large high-throughput microarray-based screening study. The key steps for biomarker identification are discussed in det…

Coordinates in the Universe of Node-Negative Breast Cancer Revisited

Abstract We present a global picture of the natural history of node-negative breast cancer in which two of three important biological processes have outstanding prognostic consequences. We propose that the transition from slow to fast proliferation of the tumor leads to the most dramatic aggravation of prognosis. Second, immune cell infiltration is of major importance to prevent disease progression in fast-proliferating breast carcinomas, regardless of estrogen receptor status. In the absence of endocrine treatment, steroid hormone receptor expression as a third axis is of limited prognostic importance. Dissecting tumors according to these three major biological axes will allow further unde…

AGO Algorithms for the Treatment of Breast Cancer: Update 2021

Geburtshilfe und Frauenheilkunde 81(10), 1101-1111 (2021). doi:10.1055/a-1519-7089

Efficacy of trastuzumab re-therapy in routine treatment of HER2-positive breast cancer patients who relapsed after completed (neo-)adjuvant anti-HER2 therapy.

602 Background: Addition of trastuzumab (Roche; T) to chemotherapy (CT) has improved outcomes in patients (pts) with HER2+ breast cancer at all stages, including locally advanced and metastatic disease. Anti-HER2 re-treatment with T is an increasingly used therapy option for the treatment of recurrent/metastatic breast cancer (MBC). However, limited data on T re-treatment is currently available. Methods: Patients with locally recurrent and/or MBC who received T re-therapy were included in this non-interventional study. Among 232 pts enrolled at 121 sites in Germany, 174 pts (33 locally recurrent disease, 141 MBC) were already sufficiently documented to be analyzed for efficacy of T re-ther…

Prediction of late metastasis in node-negative breast cancer.

10551 Background: Prediction of late metastasis is of clinical relevance in breast cancer. However, systematic genome-wide studies to identify genes associated with increased risk of metastasis 5 or more years after surgery are scarce. Methods: We examined the natural course of disease in three previously published cohorts (Mainz, Rotterdam, Transbig) including 766 node-negative breast cancer patients with gene array data who did not receive systemic chemotherapy in the adjuvant setting. We established a Cox regression based method adjusted for multiple testing that identified genes predicting late metastasis (5 or more years after surgery). Only those genes were accepted that showed simil…

Prognostic Effect of Epithelial Cell Adhesion Molecule Overexpression in Untreated Node-Negative Breast Cancer

Abstract Purpose: Epithelial cell adhesion molecule (Ep-CAM) recently received increased attention not only as a prognostic factor in breast cancer but also as a potential target for immunotherapy. We examined Ep-CAM expression in 402 consecutive node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting. Experimental Design: Ep-CAM expression was evaluated by immunostaining. Its prognostic effect was estimated relative to overexpression/amplification of HER-2, histologic grade, tumor size, age, and hormone receptor expression. Results: Ep-CAM status was positive in 106 (26.4%) patients. In multivariate analysis, Ep-CAM status was associated with disea…

Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) – Part 1 with Recommendations for the Screening, Diagnosis and Therapy of Breast Cancer

62. Kongress der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe, DGGG'18, Berlin, Germany, 31 Oct 2018 - 3 Nov 2018; Geburtshilfe und Frauenheilkunde 78(10), 927-948 (2018). doi:10.1055/a-0646-4522 special issue: "62. Kongress der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe, DGGG'18, Berlin, 31.10 – 03.11.2018 : Frauenheilkunde im Fokus: wissenschaftlich fundiert und der Qualität verpflichtet"

The humoral immune system has a key prognostic impact in node-negative breast cancer.

Abstract Estrogen receptor (ER) expression and proliferative activity are established prognostic factors in breast cancer. In a search for additional prognostic motifs, we analyzed the gene expression patterns of 200 tumors of patients who were not treated by systemic therapy after surgery using a discovery approach. After performing hierarchical cluster analysis, we identified coregulated genes related to the biological process of proliferation, steroid hormone receptor expression, as well as B-cell and T-cell infiltration. We calculated metagenes as a surrogate for all genes contained within a particular cluster and visualized the relative expression in relation to time to metastasis with…

Prognostic significance of interferon regulating factor 4 (IRF4) in node-negative breast cancer.

620 Background: The transcription factor IRF4 (interferon regulating factor 4) regulates immunoglobulin class switch recombination as well as plasma cell differentiation. We examined the prognostic significance of IRF4 mRNA expression in node-negative breast cancer. Methods: Microarray based gene-expression data for IRF4 (204562_at) were analysed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n=824). A meta-analysis of previously published cohorts was performed using a random effects model. Prognostic significance of IRF4 on metastasis-free survival (MFS) was examined in the whole cohort and in…

Abstract CT201: The Mutanome Engineered RNA Immuno-Therapy (MERIT) project

Abstract The Mutanome Engineered RNA Immuno-Therapy (MERIT) consortium will clinically and industrially validate a pioneering RNA-based immunotherapy concept that targets individual tumor antigens and tumor-specific mutations in triple negative breast cancer (TNBC) patients. This biomarker-guided, personalized therapy is a collaborative effort of five partners from academia and industry and is funded by the European Commission's FP7 and led by BioNTech AG. TNBC is an aggressive, molecularly heterogeneous cancer that accounts for 20% of all breast cancer patients. The 5-year survival rate is less than 80%. The molecular heterogeneity across TNBCs results in a lack of common targetable molecu…

Predicting Prognosis of Breast Cancer Patients with Brain Metastases in the BMBC Registry—Comparison of Three Different GPA Prognostic Scores

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) registry. The median age at diagnosis of BM was 57 years. All in all, 22.3% of patients (n = 197) had triple-negative, 33.4% (n = 295) luminal A like, 25.1% (n = 221) luminal B/HER2-enriched like and 19.2% (n = 169) HER2 positive like BC. Age ≥60 years, evidence of extracranial metastases (ECM), higher number of BM, triple-negative subtype and l…

Median progression free survival (PFS) for patients treated with everolimus (EVE) plus exemestane (EXE) for HR plus mBC in routine clinical practice : Results of the 3rd interim analysis of the non-interventional trial BRAWO

e12547 Background: BRAWO is a non-interventional study, which enrolled more than 2400 patients (pts) with advanced/metastatic, hormone-receptor-positive and HER2-negative breast cancer treated with EVE and EXE. Main objectives are a) the impact of physical activity on efficacy and quality of life, b) prophylaxis and management of stomatitis in clinical routine, and c) the sequence of therapy when EVE is used in daily clinical practice. We report updated data of the 3rd interim analysis, including PFS. Methods: This updated analysis (data cut-off 18 Oct 2016) covers data of the first 1345 documented pts with at least one follow up under therapy. Here we describe the baseline characteristics…

Abstract CT301: A phase Ib study to evaluate RO7198457, an individualized Neoantigen Specific immunoTherapy (iNeST), in combination with atezolizumab in patients with locally advanced or metastatic solid tumors

Abstract Background: Neoantigens arising from somatic mutations are attractive targets for cancer immunotherapy as they may be recognized as foreign by the immune system. RO7198457, a systemically administered RNA-Lipoplex iNeST was designed to stimulate T cell responses against neoantigens. A first-in-human Phase Ib study of RO7198457, in combination with the aPD-L1 antibody atezolizumab is being conducted in patients with locally advanced or metastatic solid tumors. Methods: RO7198457 is manufactured on a per-patient basis and contains up to 20 tumor-specific neoepitopes. Nine doses of RO7198457 were administered i.v. in weekly and bi-weekly intervals during the 12-week induction stage an…

Sorafenib (SOR) plus docetaxel (DOC) as first-line therapy in patients with HER2-negative metastatic breast cancer (MBC): A randomized, placebo-controlled phase II trial.

1072 Background: Anti-angiogenic therapy with the monoclonal anti-VEGF antibody Bevacizumab (Bev) in combination with chemotherapy increases overall response rates (ORR) and progression free surviv...

Three-arm randomized phase II study evaluating oral vinorelbine plus capecitabine versus paclitaxel plus gemcitabine versus docetaxel plus gemcitabine as first-line chemotherapy in patients with metastatic breast cancer: Final results (NorCap-CA223 trial)

1044 Background: Combination chemotherapy (CT) is among the standard treatment options in metastatic breast cancer (MBC), especially in patients (pts) with visceral metastases or need of rapid symp...

Treatment of Advanced Hormone Receptor-Positive (HR+) HER2-negative Breast Cancer

AbstractThe article gives an overview of current treatment options for metastatic hormone receptor-positive and HER2-negative breast cancer. The focus is on combined therapies, e.g., with CDK4/6 inhibition compared with purely endocrine-based therapies in the pre- and postmenopause, presenting the latest study results. The addition of a CDK4/6 inhibitor to endocrine-based therapy with an aromatase inhibitor or fulvestrant leads to a marked improvement in progression-free survival and is independently beneficial whether palbociclib, ribociclib or abemaciclib is involved. The particular clinical status of inhibition of cyclin-dependent kinases argues for its use in the first-line treatment of…

Epithelioides Hämangioendotheliom der Wirbelsäule

Hintergrund: Epithelioide Hamangioendotheliome sind seltene vaskulare Tumoren, die bevorzugt im Bindegewebe, in der Lunge oder in der Leber auftreten. Falldarstellung: Wir prasentieren den Fall einer 58-jahrigen Patientin, die mit oberer Einflussstauung, Horner-Syndrom und segmentalen Sensibilitatsstorungen in den Fingern der rechten Hand aufgenommen wurde. Die daraufhin durchgefuhrten Computertomographie- und Magnetresonanztomographieuntersuchungen der Wirbelsaule zeigten eine tumorose Raumforderung vom siebten Halswirbelkorper bis zum vierten Brustwirbelkorper. Wegen rascher Tumorprogression mit progredienter oberer Einflussstauung und neurologischen Ausfallen musste die Patientin wiederh…

Loss of circadian clock gene expression is associated with tumor progression in breast cancer

Several studies suggest a link between circadian rhythm disturbances and tumorigenesis. However, the association between circadian clock genes and prognosis in breast cancer has not been systematically studied. Therefore, we examined the expression of 17 clock components in tumors from 766 node-negative breast cancer patients that were untreated in both neoadjuvant and adjuvant settings. In addition, their association with metastasis-free survival (MFS) and correlation to clinicopathological parameters were investigated. Aiming to estimate functionality of the clockwork, we studied clock gene expression relationships by correlation analysis. Higher expression of several clock genes (e.g., C…