References of "Jerusalem, Guy"
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See detailBIOPSIE DES LESIONS SUSPECTES CHEZ LES PATIENTS AYANT PRESENTE UN CANCER DU SEIN.
Colin, P.-E.; Schroeder, H.; Gonne, E. et al

in Revue medicale de Liege (2015), 70(11), 563-8

Discordances between hormone receptors and HER2 status in primary and metastatic breast cancer have been reported by several studies. In this context, systematic biopsies could be clinically relevant in ... [more ▼]

Discordances between hormone receptors and HER2 status in primary and metastatic breast cancer have been reported by several studies. In this context, systematic biopsies could be clinically relevant in breast cancer to confirm the biological characteristics of a suspicious lesion. In this article, illustrated by 2 case reports and based on a recent review on this topic, we discuss the clinical significance of receptor discordances and possible diagnosis of a secondary primary tumor. The role of these biopsies for the identification of new therapeutic targets is also envisaged as well as underlying mechanisms for receptors' modification like tumoral heterogeneity, clonal selection and technical artifacts. [less ▲]

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See detailPredictive biomarkers of everolimus efficacy in HER2+ advanced breast cancer : combined exploratory analysis from BOLERO-1 and BOLERO-3
Slamon, Dennis; Hurvitz, Sara; Chen, David et al

in Journal of Clinical Oncology (2015), 33(suppl ; abstr 512),

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See detailImplementation of geriatric assessment - based recommendations in older patients with cancer : a multicenter prospective study
Baitar, A; Kenis, C; Moor, R et al

in Journal of Geriatric Oncology (2015), 6

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See detailEffect of itraconazole and rifampin on the pharmacokinetics of olaparib table formulation in patients with advanced solid tumors : phase I open-label studies
Plummer, Elizabeth R.; Verheul, Henk M.W.; Rottey, Sylvie et al

in Journal of Clinical Oncology (2015), 33(suppl : abstr 2565),

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See detailRelationship of germline polymorphisms to docetaxel toxicity in the ROSE/TRIO-012 trial
Damaraju, Sambasivarao; Gorbunova, Vera; Gelmon, Karen A. et al

in Journal of Clinical Oncology (2015), (suppl abstr 540),

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See detailA nationwide implementation of a multidisciplinary geriatric assessment and intervention program in belgian older patients with cancer
Kenis, C; Flamaing, J; Debruyne, P.R. et al

in Journal of Geriatric Oncology (2015), 6(S13-S27), 001

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See detailAvelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with metastatic or locally advanced solid tumors : assessment of safety and tolerability in a phase I, open-label expansion study
Kelly, Karen; Patel, Manish R.; Infante, Jeffrey R. et al

in Journal of Clinical Oncology (2015), 33(suppl ; abstr 3044),

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See detailPatterns of resource utilization and cost for postmenopausal women with hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer in Europe.
Jerusalem, Guy ULiege; Neven, Patrick; Marinsek, Nina et al

in BMC cancer (2015), 15

BACKGROUND: Healthcare resource utilization in breast cancer varies by disease characteristics and treatment choices. However, lack of clarity in guidelines can result in varied interpretation and ... [more ▼]

BACKGROUND: Healthcare resource utilization in breast cancer varies by disease characteristics and treatment choices. However, lack of clarity in guidelines can result in varied interpretation and heterogeneous treatment management and costs. In Europe, the extent of this variability is unclear. Therefore, evaluation of chemotherapy use and costs versus hormone therapy across Europe is needed. METHODS: This retrospective chart review (N = 355) examined primarily direct costs for chemotherapy versus hormone therapy in postmenopausal women with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer across 5 European countries (France, Germany, The Netherlands, Belgium, and Sweden). RESULTS: Total direct costs across the first 3 treatment lines were approximately euro10 000 to euro14 000 lower for an additional line of hormone therapy-based treatment versus switching to chemotherapy-based treatment. Direct cost difference between chemotherapy-based and hormone therapy-based regimens was approximately euro1900 to euro2500 per month. Chemotherapy-based regimens were associated with increased resource utilization (managing side effects; concomitant targeted therapy use; and increased frequencies of hospitalizations, provider visits, and monitoring tests). The proportion of patients taking sick leave doubled after switching from hormone therapy to chemotherapy. CONCLUSIONS: These results suggest chemotherapy is associated with increased direct costs and potentially with increased indirect costs (lower productivity of working patients) versus hormone therapy in HR+, HER2- advanced breast cancer. [less ▲]

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See detailAsporin Is a Fibroblast-Derived TGF-beta1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer.
Maris, Pamela; Blomme, Arnaud; Palacios, Ana Perez et al

in PLoS medicine (2015), 12(9), 1001871

BACKGROUND: Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity is caused by metastases that remain incurable to date. TGF-beta1 has been identified as a key ... [more ▼]

BACKGROUND: Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity is caused by metastases that remain incurable to date. TGF-beta1 has been identified as a key driving force behind metastatic breast cancer, with promising therapeutic implications. METHODS AND FINDINGS: Employing immunohistochemistry (IHC) analysis, we report, to our knowledge for the first time, that asporin is overexpressed in the stroma of most human breast cancers and is not expressed in normal breast tissue. In vitro, asporin is secreted by breast fibroblasts upon exposure to conditioned medium from some but not all human breast cancer cells. While hormone receptor (HR) positive cells cause strong asporin expression, triple-negative breast cancer (TNBC) cells suppress it. Further, our findings show that soluble IL-1beta, secreted by TNBC cells, is responsible for inhibiting asporin in normal and cancer-associated fibroblasts. Using recombinant protein, as well as a synthetic peptide fragment, we demonstrate the ability of asporin to inhibit TGF-beta1-mediated SMAD2 phosphorylation, epithelial to mesenchymal transition, and stemness in breast cancer cells. In two in vivo murine models of TNBC, we observed that tumors expressing asporin exhibit significantly reduced growth (2-fold; p = 0.01) and metastatic properties (3-fold; p = 0.045). A retrospective IHC study performed on human breast carcinoma (n = 180) demonstrates that asporin expression is lowest in TNBC and HER2+ tumors, while HR+ tumors have significantly higher asporin expression (4-fold; p = 0.001). Assessment of asporin expression and patient outcome (n = 60; 10-y follow-up) shows that low protein levels in the primary breast lesion significantly delineate patients with bad outcome regardless of the tumor HR status (area under the curve = 0.87; 95% CI 0.78-0.96; p = 0.0001). Survival analysis, based on gene expression (n = 375; 25-y follow-up), confirmed that low asporin levels are associated with a reduced likelihood of survival (hazard ratio = 0.58; 95% CI 0.37-0.91; p = 0.017). Although these data highlight the potential of asporin to serve as a prognostic marker, confirmation of the clinical value would require a prospective study on a much larger patient cohort. CONCLUSIONS: Our data show that asporin is a stroma-derived inhibitor of TGF-beta1 and a tumor suppressor in breast cancer. High asporin expression is significantly associated with less aggressive tumors, stratifying patients according to the clinical outcome. Future pre-clinical studies should consider options for increasing asporin expression in TNBC as a promising strategy for targeted therapy. [less ▲]

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See detailImplementation of geriatric assessment-based recommendations in older patients with cancer: A multicentre prospective study
Baitar, Abdelbari; Kenis, Cindy; Moor, Ramona et al

in Journal of geriatric oncology (2015), 6(5), 401-10

PURPOSE: The main objective of this study was to describe geriatric recommendations based on a geriatric assessment (GA) and to evaluate the implementation of these recommendations. PATIENTS AND METHODS ... [more ▼]

PURPOSE: The main objective of this study was to describe geriatric recommendations based on a geriatric assessment (GA) and to evaluate the implementation of these recommendations. PATIENTS AND METHODS: A two-step approach of screening followed by a GA was implemented in nine hospitals in Belgium. Patients >/=70years were included at diagnosis or at disease progression/relapse. Concrete geriatric recommendations were systematically documented and reported to the treating physicians and consisted of referrals to professional health care workers. Patient charts were reviewed after one month to verify which geriatric recommendations have been performed. RESULTS: From August 2011 to July 2012, 1550 patients were included for analysis. The median age was 77 (range: 70-97) and 57.0% were female. A solid tumour was diagnosed in 91.4% and a haematological malignancy in 8.6%. Geriatric screening with the G8 identified 63.6% of the patients for GA (n=986). A median of two geriatric recommendations (range: 1-6) were given for 76.2% (95%CI: 73.4-78.8) of the evaluable patients (n=710). A median of one geriatric recommendation (range: 1-5) was performed in 52.1% (95%CI: 48.4-55.8) of the evaluable patients (n=689). In general, 460 or 35.3% (95%CI: 32.8-38.0) of all the geriatric recommendations were performed. Geriatric recommendations most frequently consisted of referrals to the dietician (60.4%), social worker (40.3%), and psychologist (28.9%). CONCLUSION: This implementation study provides insight into GA-based recommendations/interventions in daily oncology practice. Geriatric recommendations were given in about three-fourths of patients. About one-third of all geriatric recommendations were performed in approximately half of these patients. [less ▲]

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See detailOlaparib tablet formulation : effect of food on the pharmacokinetics after oral dosing in patients with advanced solid tumours
Plummer, Ruth; Swaisland, Helen; Leunen, Karin et al

in Cancer Chemotherapy & Pharmacology (2015), 76

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See detailGenetic study of triple negative breast cancers
Boukerroucha, M; Josse, Claire ULiege; El Guendi, Sonia ULiege et al

Poster (2015)

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See detailVISMODEGIB ET CARCINOMES BASOCELLULAIRES LOCALEMENT AVANCES
LEBAS, Eglantine ULiege; RORIVE, Andrée ULiege; EL HAYDERI, Lara ULiege et al

in Revue Médicale de Liège (2015)

Basal cell carcinoma is the most frequent skin cancer. Even though metastases are exceptional, these cancers may be locally highly aggressive. The Hedgehog signaling pathway plays a significant role in ... [more ▼]

Basal cell carcinoma is the most frequent skin cancer. Even though metastases are exceptional, these cancers may be locally highly aggressive. The Hedgehog signaling pathway plays a significant role in the pathogenesis of basal cell carcinoma. Vismodegib is a selective inhibitor of this pathway and may be administered orally. Its main indication is locally advanced basal cell carcinoma, when other therapeutic options have failed or are contra-indicated. Vismodegib can also be used as prophylactic therapy in the Gorlin syndrome or basal cell nevomatosis. Its principal adverse effects are muscle spasms, alopecia and altered taste. They are frequent, but often moderate in intensity; they sometimes restrict continuation of treatment. Two clinical cases are presented, relating the efficacity and tolerance of this new therapeutic option. [less ▲]

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See detailEndothelial exosomes contribute to the antitumor response during breast cancer neoadjuvant chemotherapy via microRNA transfer.
Bovy, Nicolas ULiege; Blomme, Benoît ULiege; Freres, Pierre ULiege et al

in Oncotarget (2015)

The interaction between tumor cells and their microenvironment is an essential aspect of tumor development. Therefore, understanding how this microenvironment communicates with tumor cells is crucial for ... [more ▼]

The interaction between tumor cells and their microenvironment is an essential aspect of tumor development. Therefore, understanding how this microenvironment communicates with tumor cells is crucial for the development of new anti-cancer therapies. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression. They are secreted into the extracellular medium in vesicles called exosomes, which allow communication between cells via the transfer of their cargo. Consequently, we hypothesized that circulating endothelial miRNAs could be transferred to tumor cells and modify their phenotype. Using exogenous miRNA, we demonstrated that endothelial cells can transfer miRNA to tumor cells via exosomes. Using miRNA profiling, we identified miR-503, which exhibited downregulated levels in exosomes released from endothelial cells cultured under tumoral conditions. The modulation of miR-503 in breast cancer cells altered their proliferative and invasive capacities. We then identified two targets of miR-503, CCND2 and CCND3. Moreover, we measured increased plasmatic miR-503 in breast cancer patients after neoadjuvant chemotherapy, which could be partly due to increased miRNA secretion by endothelial cells. Taken together, our data are the first to reveal the involvement of the endothelium in the modulation of tumor development via the secretion of circulating miR-503 in response to chemotherapy treatment. [less ▲]

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See detailEACVI/HFA Cardiac Oncology Toxicity Registry in breast cancer patients: rationale, study design, and methodology (EACVI/HFA COT Registry)-EURObservational Research Program of the European Society of Cardiology.
Lancellotti, Patrizio ULiege; Anker, Stefan D.; Donal, Erwan et al

in European Heart Journal - Cardiovascular Imaging (2015)

The goal of adjuvant anti-cancer therapies is cure with limited or no side effects, in particular long-term side effects with negative impact on quality of life. In the palliative setting disease control ... [more ▼]

The goal of adjuvant anti-cancer therapies is cure with limited or no side effects, in particular long-term side effects with negative impact on quality of life. In the palliative setting disease control, quality of life and overall survival are important end points. Partly due to improvements in treatment, the population of cancer survivors is large and growing. However, anti-cancer drug-related cardiotoxicity (ADRC) is the leading cause of treatment-associated mortality in cancer survivors. It is one of the most common post-treatment problems among 5- to 10-year survivors of adult cancer. This is particularly true for breast cancer, the most common cancer in women. The EACVI/HFA COT registry is designed for comprehensive data collection and evaluation of the current European practice in terms of diagnosis and management of ADRC in breast cancer patients. The COT registry will be carried out in two continuing phases, the pilot study phase involving 13 countries followed by the long-term registry in which all the 56 ESC countries will be invited to participate. With the COT registry, several critical information will be obtained: on predisposing factors for the development of ADRC, the rate of subclinical LV dysfunction and its transition to overt heart failure, the clinical impact and outcome of ADRC. [less ▲]

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See detailPrise en charge de la neutropénie fébrile chez le patient cancéreux
FRERES, Pierre ULiege; GONNE, Elodie ULiege; COLLIGNON, Joëlle ULiege et al

in Revue Médicale de Liège (2015), 70(4), 195-200

Les cancers sont de plus en plus fréquents et leurs traitements de plus en plus agressifs. En conséquence, médecins généralistes, urgentistes, hématologues et oncologues se trouvent régulièrement ... [more ▼]

Les cancers sont de plus en plus fréquents et leurs traitements de plus en plus agressifs. En conséquence, médecins généralistes, urgentistes, hématologues et oncologues se trouvent régulièrement confrontés à un effet secondaire sévère des traitements cytotoxiques, le neutropénie fébrile (NF). La NF est une complication gravissime de la chimiothérapie, car elle peut être rapidement mortelle et provoque un arrêt temporaire, voire définitif, des traitements. Dans cet article, nous résumons les dernières recommandations quant à la prise en charge thérapeutique des patients présentant une NF sous traitements anti-cancéreux. [less ▲]

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See detailCancer du sein : de la thérapie ciblée à la médecine personnalisée
JERUSALEM, Guy ULiege; COLLIGNON, Joëlle ULiege; Josse, Claire ULiege et al

in Revue Médicale de Liège (2015), 70(5-6), 269-276

Dans cet article, les auteurs passent en revue les grands principes de prise en charge du traitement systémique du cancer du sein et posent la question suivante : jusqu'où réellement aujourd'hui ce ... [more ▼]

Dans cet article, les auteurs passent en revue les grands principes de prise en charge du traitement systémique du cancer du sein et posent la question suivante : jusqu'où réellement aujourd'hui ce traitement est-il individualisé ? Les nouvelles technologies permettent une analyse détaillée des anomalies génomiques au niveau des cellules cancéreuses. Malheureusement, nous n'avons pas encore compris comment utiliser au mieux ces données au bénéfice du patient. La majorité des modifications du génome sont des évènements relativement rares compliquant le développement de nouveaux médicaments dans le cadre d'une médecine de précision. De plus, les tumeurs présentent une grande hétérogénéité temporelle et spatiale dont il faudra tenir compte lors de ce développement. Une collaboration internationale intensive est en cours pour tenter de confirmer que la médecine de précision permet d'optimiser les résultats du traitement systémique dans le cancer du sein. [less ▲]

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See detailA network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer.
Generali, Daniele; Venturini, Sergio; Rognoni, Carla et al

in Breast cancer research and treatment (2015), 152(1), 95-117

The goal of this study was to compare the efficacy and toxicity of chemotherapy to exemestane plus everolimus (EXE/EVE) through a network meta-analysis (NMA) of randomized controlled trials. NMA methods ... [more ▼]

The goal of this study was to compare the efficacy and toxicity of chemotherapy to exemestane plus everolimus (EXE/EVE) through a network meta-analysis (NMA) of randomized controlled trials. NMA methods extend standard pairwise meta-analysis to allow simultaneous comparison of multiple treatments while maintaining randomization of individual studies. The method enables "direct" evidence (i.e., evidence from studies directly comparing two interventions) and "indirect" evidence (i.e., evidence from studies that do not compare the two interventions directly) to be pooled under the assumption of evidence consistency. We used NMA to evaluate progression-free survival (PFS) and time to progression (TTP) curves in 34 studies, and response rate (RR) and the hazard ratios (HRs) of the PFS/TTP in 36 studies. A number needed to treat (NNT) analysis was also performed as well as descriptive comparison of reported toxicities. The NMA for PFS/TTP curves and for HR shows EXE/EVE is more efficacious than capecitabine plus sunitinib, CMF, megestrol acetate and tamoxifen, with an average of related-PFS/TTP difference ranging from about 10 months for capecitabine plus sunitinib to more than 6 months for tamoxifen. The NMA for overall RR shows that EXE/EVE provides a better RR than bevacizumab plus capecitabine, capecitabine, capecitabine plus sorafenib, capecitabine plus sunitinib, CMF, gemcitabine plus epirubicin plus paclitaxel, EVE plus tamoxifen, EXE, FEC, megestrol acetate, mitoxantrone, and tamoxifen. Finally, the NMA for NNT shows that EXE/EVE is more beneficial as compared to BMF, capecitabine, capecitabine plus sunitinib, CMF, FEC, megestrol acetate, mitoxantrone, and tamoxifen. The combination of EXE/EVE as first- or second-line therapy for ER+ve/HER2-ve metastatic breast cancer is more efficacious than several chemotherapy regimens that were reported in the literature. Toxicities also favored EXE/EVE in most instances. [less ▲]

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See detailChemotherapy options for patients suffering from heavily pretreated metastatic breast cancer.
Jerusalem, Guy ULiege; RORIVE, Andrée ULiege; COLLIGNON, Joëlle ULiege

in Future oncology (London, England) (2015), 11(12), 1775-89

ABSTRACT The identification of additional chemotherapy agents for anthracycline- and taxane-pretreated advanced breast cancer (ABC) is an urgent medical need. Single agent chemotherapy is most times ... [more ▼]

ABSTRACT The identification of additional chemotherapy agents for anthracycline- and taxane-pretreated advanced breast cancer (ABC) is an urgent medical need. Single agent chemotherapy is most times administered because combined therapy is only associated with modest, if any, improvement in median progression-free survival. Randomized trials failed to show overall survival benefit compared with single agent chemotherapy. We hope to modify the natural history of ABC by the consecutive use of treatments with documented activity in heavily pretreated patients. Quality of life remains an important end point as cure is in general not possible. We first review the activity of the approved and the most frequently used agents in heavily pretreated ABC. Thereafter, the potential role and safety profile of etirinotecan pegol is discussed given the results recently released of a Phase III trial comparing this agent to Treatment of Physician's Choice. [less ▲]

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