Publications of Eric LIFRANGE
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See detailCirculating microRNA-based screening tool for breast cancer
Freres, Pierre ULiege; Wenric, Stéphane ULiege; BOUKERROUCHA, Meriem ULiege et al

in Oncotarget (2015)

Circulating microRNAs (miRNAs) are increasingly recognized as powerful biomarkers in several pathologies, including breast cancer. Here, their plasmatic levels were measured to be used as an alternative ... [more ▼]

Circulating microRNAs (miRNAs) are increasingly recognized as powerful biomarkers in several pathologies, including breast cancer. Here, their plasmatic levels were measured to be used as an alternative screening procedure to mammography for breast cancer diagnosis. A plasma miRNA profile was determined by RT-qPCR in a cohort of 378 women. A diagnostic model was designed based on the expression of 8 miRNAs measured first in a profiling cohort composed of 41 primary breast cancers and 45 controls, and further validated in diverse cohorts composed of 108 primary breast cancers, 88 controls, 35 breast cancers in remission, 31 metastatic breast cancers and 30 gynecologic tumors. A receiver operating characteristic curve derived from the 8-miRNA random forest based diagnostic tool exhibited an area under the curve of 0.81. The accuracy of the diagnostic tool remained unchanged considering age and tumor stage. The miRNA signature correctly identified patients with metastatic breast cancer. The use of the classification model on cohorts of patients with breast cancers in remission and with gynecologic cancers yielded prediction distributions similar to that of the control group. Using a multivariate supervised learning method and a set of 8 circulating miRNAs, we designed an accurate, minimally invasive screening tool for breast cancer. [less ▲]

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See detailMyoferlin Regulates Endosomal Trafficking and Tunes Cancer Cell Metabolism
Blomme, Arnaud ULiege; Costanza, Brunella ULiege; Thiry, Marc ULiege et al

Poster (2015, January 31)

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See detailMyoferlin regulates endosomal trafficking and tunes cancer cell metabolism
Blomme, Arnaud ULiege; Costanza, Brunella ULiege; Thiry, Marc ULiege et al

Poster (2015, January 27)

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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 ULiege; 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 detailMyoferlin is a key regulator of EGFR activity in breast cancer.
Turtoi, Andrei ULiege; Blomme, Arnaud ULiege; Bellahcene, Akeila ULiege et al

in Cancer Research (2013), 73

Myoferlin is a member of the ferlin family of proteins that participate in plasma membrane fusion, repair and endocytosis. While some reports have implicated myoferlin in cancer, the extent of its ... [more ▼]

Myoferlin is a member of the ferlin family of proteins that participate in plasma membrane fusion, repair and endocytosis. While some reports have implicated myoferlin in cancer, the extent of its expression in and contributions to cancer are not well established. In this study, we show that myoferlin is overexpressed in human breast cancers and that it is has a critical role in controlling degradation of the EGFR after its activation and internalization in breast cancer cells. Myoferlin depletion blocked EGF-induced cell migration and epithelial-to-mesenchymal transition. Both effects were induced as a result of impaired degradation of phosphorylated EGFR via dysfunctional plasma membrane caveolae and alteration of caveolin homooligomerization. In parallel, myoferlin depletion reduced tumor development in a chicken chorioallantoic membrane xenograft model of human breast cancer. Considering the therapeutic significance of EGFR targeting, our findings identify myoferlin as an novel candidate function to target for future drug development. [less ▲]

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See detailThe cancer screening controversy
CUSUMANO, Giuseppe ULiege; LIFRANGE, Eric ULiege

in European Journal of Cancer Prevention (2011), Suppl 1(S1),

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See detailLa chirurgie oncoplastique du sein.
BOUS, Aurélie ULiege; NARDELLA, Daniele ULiege; MAWEJA, Sylvie ULiege et al

in Revue Médicale de Liège (2011), 66(5-6), 341-50

Oncoplastic surgery combines large lumpectomy and defect remodeling by different plastic surgery methods. These procedures improve the cosmetic result after partial mastectomy and widens the possibilities ... [more ▼]

Oncoplastic surgery combines large lumpectomy and defect remodeling by different plastic surgery methods. These procedures improve the cosmetic result after partial mastectomy and widens the possibilities for conservative treatment. Different techniques are used from simple glandular remodeling to more difficult techniques for breast plasties with or without simultaneous controlateral symetrisation procedure. The surgical option depends especially on the ratio between the volume of the tumor and the volume of the breast and the position of the tumor. This more effective conservative treatment facilitates also postoperative radiotherapy, reduces the sequellae and the psychological impact of breast cancer treatment. [less ▲]

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See detailReconstruction mammaire immédiate et radiothérapie post-opératoire : une mise au point
NARDELLA, Daniele ULiege; LAUNGANI, Alexis ULiege; LIFRANGE, Eric ULiege et al

in Revue Médicale de Liège (2011), 66(5-6), 368-361

La reconstruction mammaire est actuellement partie intégrante de la prise en charge du cancer du sein. Lorsqu’elle est proposée en immédiat, plusieurs contraintes se présentent au chirurgien plasticien ... [more ▼]

La reconstruction mammaire est actuellement partie intégrante de la prise en charge du cancer du sein. Lorsqu’elle est proposée en immédiat, plusieurs contraintes se présentent au chirurgien plasticien. La prise en charge des patientes devant bénéficier d’une mastectomie se complique par les traitements complémentaires de radiothérapie. Nous proposons, dans ce travail, une prise en charge multidisciplinaire des patientes en les adressant à des sous-groupes spécifiques. Une reconstruction immédiate sera proposée à certaines patientes compte tenu des traitements complémentaires par radiothérapie. Les choix d’orientation sont complexes et une littérature pauvre à ce sujet ne nous permet pas d’orienter de façon systématique toutes les patientes. De nouvelles études, notamment prospectives, sont nécessaires pour orienter les patientes désirant une reconstruction immédiate associée à une radiothérapie post-mastectomie. [less ▲]

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See detailLe cancer du sein en Belgique: pourquoi sommes-nous les premiers en Europe?
DESREUX, Joëlle ULiege; Gaspard, Ulysse ULiege; BLERET, Valerie ULiege et al

in Revue Médicale de Liège (2011), 66(5-6), 231-7

Breast cancer incidence in Belgium is on the top of European countries, with 9.697 new cases in 2008 and 106/100.000 women/year. The explanation of this high incidence in our country is probably the ... [more ▼]

Breast cancer incidence in Belgium is on the top of European countries, with 9.697 new cases in 2008 and 106/100.000 women/year. The explanation of this high incidence in our country is probably the accumulation of risk factors (many of them are linked to lifestyle), and the impact of screening and registration of cases. The relative impact of each of theses factors is less clear because we don't have powerful statistical studies. Belgium is slightly above the European mean for breast cancer mortality, with 19,4/100.000 women/year and an all stages 15-year survival of 75%. Breast cancers are responsible for around 3% of all-cause mortality in Belgian women. This article discusses the causes of this high Belgian incidence and of current decrease of incidence in western countries, and reviews known and less known risk factors of breast cancers, with a special focus on menopause hormonal treatments. [less ▲]

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See detailPrise en charge des consequences de la carence oestrogenique apres cancer du sein.
BLERET, Valerie ULiege; PINTIAUX, Axelle ULiege; BELIARD, Aude ULiege et al

in Revue Médicale de Liège (2011), 66(5-6), 385-92

The prevention and the treatment of oestrogen deficiency induced by breast cancer treatments are crucial in the management of patients. The impacts of this deficiency must not be neglected: quality of ... [more ▼]

The prevention and the treatment of oestrogen deficiency induced by breast cancer treatments are crucial in the management of patients. The impacts of this deficiency must not be neglected: quality of life impairments inducing eventually premature withdrawal of hormonotherapies, and excess of bone and cardio-vascular morbidities and mortalities, especially in good prognosis young women. Management strategies of short and long term effects of this deficiency are reviewed and discussed here. [less ▲]

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See detailMastectomie bilaterale prophylactique chez les patientes a tres haut risque de cancer mammaire: au-dela de la technique...
BLERET, Valerie ULiege; Cusumano, P.; DEZFOULIAN, Bahram ULiege et al

in Revue Médicale de Liège (2011), 66(5-6), 250-3

Bilateral prophylactic mastectomy is the most efficient risk management strategy for women at very high risk for breast cancer. Different methods can be used. The implementation of such a strategy must ... [more ▼]

Bilateral prophylactic mastectomy is the most efficient risk management strategy for women at very high risk for breast cancer. Different methods can be used. The implementation of such a strategy must respond to the request of a well informed patient. [less ▲]

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See detailAccelerated partial breast irradiation: state of the art
COUCKE, Philippe ULiege; JANSEN, Nicolas ULiege; JANVARY, Zsolt Levente ULiege et al

in Belgian Journal of Medical Oncology (2011), 5(1), 3-7

Accelerated partial breast irradiation can be applied by means of different techniques. It <br />offers an opportunity for reducing the treatment duration considerably and harbours the <br />potential for ... [more ▼]

Accelerated partial breast irradiation can be applied by means of different techniques. It <br />offers an opportunity for reducing the treatment duration considerably and harbours the <br />potential for less exposure of healthy tissue to higher radiation doses. However, evidence <br />issued from randomized trials is limited. European and American experts call our attention <br />to the potential dangers of widespread implementation of these techniques without any <br />long-term data on outcome and ask for complete information of patients on the potential <br />hazards and risks if accelerated partial breast irradiation is used instead of whole breast <br />irradiation. [less ▲]

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See detailGanglion sentinelle et sentibras: pour un "staging" axillaire sur mesure
Cusumano, P.; BLERET, Valerie ULiege; Nos, C. et al

in Revue Médicale de Liège (2011), 66(5-6), 336-40

The status of the axillary lymph nodes is one of the most important prognostic factors in women with early stage breast cancer. Histologic examination of removed lymph nodes is the most accurate method ... [more ▼]

The status of the axillary lymph nodes is one of the most important prognostic factors in women with early stage breast cancer. Histologic examination of removed lymph nodes is the most accurate method for assessing spread of disease to these nodes. Axillary lymph node dissection (ALND) remains the standard approach for women who have clinically palpable axillary nodes. The benefits of ALND include its impact on disease control (axillary recurrence and survival), its prognostic value, and its role in treatment selection. However, the anatomic disruption caused by ALND may result in lymphedema, nerve injury, and shoulder dysfunction, which compromise functionality and quality of life. For patients who have clinically negative axillary lymph nodes, sentinel lymph node (SLN) biopsy offers a less morbid method to determine if there are positive nodes, in which case axillary node dissection would be necessary. Patients who are SLN-positive should undergo complete ALND. Axillary reverse mapping (ARM) is a recent improvement of ALND which, like the biopsy of the GS, would reduce morbidity. [less ▲]

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See detailPrevention primaire et secondaire chez les femmes a haut risque de cancer mammaire.
BLERET, Valerie ULiege; DESREUX, Joëlle ULiege; Cusumano, P et al

in Revue Médicale de Liège (2011), 66(5-6), 245-9

Many factors determine a woman's risk of breast cancer; some genetic are related to family history, others are based on personal factors such reproductive and medical history. A high-risk woman must ... [more ▼]

Many factors determine a woman's risk of breast cancer; some genetic are related to family history, others are based on personal factors such reproductive and medical history. A high-risk woman must benefit of a specific screening regimen including breast examination, mammography, ultrasonography and contrast material-enhanced magnetic resonance. But she can also benefit of chemo prevention or/and risk-reducing surgery such bilateral prophylactic salpingo-oophorectomy and bilateral prophylactic mastectomy. [less ▲]

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See detailLe cancer du sein chez la femme jeune
ANDRE, Chantal ULiege; COLLIGNON, Joëlle ULiege; RORIVE, Andrée ULiege et al

in Revue Médicale de Liège (2011), 66(5-6), 397-399

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See detailL'observance au traitement de longue durée : le cas particulier de l'hormonothérapie adjuvante du cancer du sein
Bleret, Valerie ULiege; Collignon, Joëlle ULiege; Coucke, Philippe ULiege et al

in Revue Médicale de Liège (2010), 65(5-6), 405-408

L'objectif de l'hormonothérapie adjuvante dans le cancer du sein est d'atteindre en pratique quotidiennee, une efficacité comparable à celle obtenue au cours des études cliniques. Malgré l'efficacité ... [more ▼]

L'objectif de l'hormonothérapie adjuvante dans le cancer du sein est d'atteindre en pratique quotidiennee, une efficacité comparable à celle obtenue au cours des études cliniques. Malgré l'efficacité démontrée de l'hormonothérapie, la compliance constitue un défi majeur et un problème multidimensionnel. Une meilleure compréhension des raisons de cette non-compliance aiderait à mieux identifier les patientes à risque et à développer des interventions capables d'améliorer l'adhésion à l'hormonothérapie adjuvante.C'est dans ce but que nous avons entrepris une revue de la littérature des six dernières années (Pub Med 2003-2006). [less ▲]

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See detailANTICORPS MONOCLONAUX ET CANCER DU SEIN: Actualités thérapeutiques
Collignon, Joëlle ULiege; Gennigens, Christine ULiege; Rorive, Andrée ULiege et al

in Revue Médicale de Liège (2009), 64(5-6), 279-83

About 9,500 new breast cancers are diagnosed in Belgium every year. Improvement of our knowledge of altered molecular events leading to the proliferation of tumor cells has resulted in the development of ... [more ▼]

About 9,500 new breast cancers are diagnosed in Belgium every year. Improvement of our knowledge of altered molecular events leading to the proliferation of tumor cells has resulted in the development of targeted therapies in subgroups of cancers. One of the first validation of targeted therapy is the anti-HER-2 monoclonal antibody trastuzumab (Herceptin) in patients with overexpression of human epidermal growth factor receptor type 2 (HER2) occurring in 20 to 25% of invasive breast carcinoma. Trastuzumab binds the extracellular juxtamembrane domain and is only active in tumor with HER2 gene amplification detected by fluorescence in situ hybridization (FISH). The results from randomized trials have rapidly lead to the approvement of the drug in the metastatic and then in the adjuvant setting. Another targeted therapy, also approved in the treatment of breast cancer, is the monoclonal antibody bevacizumab with an anti-VEGF (Vascular Endothelial Growth Factor) activity. We will review the benefit of these targeted therapies in breast cancer and their role in the treatment of breast cancer. [less ▲]

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See detailActualites therapeutiques en gynecologie: pathologies organiques
HERMAN, Philippe ULiege; Lifrange, Eric ULiege; Nisolle, Michelle ULiege et al

in Revue Médicale de Liège (2007), 62(5-6, May-Jun), 414-22

Over the last ten years, progress in evidence-based medicine coupled with technological and surgical breakthroughs have deeply changed the management of our patients. Uterine bleeding is the first cause ... [more ▼]

Over the last ten years, progress in evidence-based medicine coupled with technological and surgical breakthroughs have deeply changed the management of our patients. Uterine bleeding is the first cause of gynaecological consultation and the intrauterine progestin delivery system as well as new hysteroscopic procedures have optimized the therapeutic approach to this problem. Introduction of magnetic resonance imaging and interventional procedures have improved breast disease diagnosis and management; likewise sentinel node localization, introduction of aromatase and growth factors inhibitors, new radiotherapy procedures and pharmacogenomics, have helped to ameliorate breast cancer treatment. Pelvic surgery has been switching more and more towards laparoscopic procedures not only in the field of benign lesions (eg endometriosis), of surgery of prolapse and incontinence with new prosthetic materials, but also for an improved management of gynaecological cancers. [less ▲]

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See detailDefining the role of aromatase inhibitors in the adjuvant endocrine treatment of early breast cancer
BUDZAR, A.; CHLEBOWSKI, R.; CUZICK, J. et al

in Current Medical Research and Opinion (2006), 22

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