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See detailPredictive and prognostic role of peripheral blood eosinophil count in triple-negative and hormone receptor-negative/HER2-positive breast cancer patients undergoing neoadjuvant treatment
ONESTI, Concetta Elisa ULiege; JOSSE, Claire ULiege; Poncin, Aurélie ULiege et al

in Oncotarget (2018)

In current clinical practices, up to 27% of all breast cancer patients receive neoadjuvant chemotherapy. High pathological complete response rate is frequently associated with tumor-infiltrating ... [more ▼]

In current clinical practices, up to 27% of all breast cancer patients receive neoadjuvant chemotherapy. High pathological complete response rate is frequently associated with tumor-infiltrating lymphocytes. Additionally, circulating immune cells are also often linked to chemotherapy response. We performed a retrospective analysis on a cohort of 112 breast cancer patients (79 triple-negative, 33 hormone receptor-negative/HER2-positive) treated with standard neoadjuvant chemotherapy. Eosinophil and lymphocyte counts were collected from whole blood at baseline and during follow-ups and their associations with pathological complete response, relapse, disease-free and breast cancer-specific survival were analyzed. We observed a higher pathological complete response rate in patients who presented at baseline a relative eosinophil count ≥ 1.5% (55.6%) than in those with a relative eosinophil count < 1.5% (36.2%)(p = 0.04). An improvement in breast cancerspecific survival in patients with high relative eosinophil count (p = 0.05; HR = 0.336; 95% CI = 0.107–1.058) or with high relative lymphocyte count (threshold = 17.5%, p = 0.01; HR = 0.217; 95% CI = 0.060–0.783) were also observed. Upon combining the two parameters into the eosinophil x lymphocyte product with a threshold at 35.8, associations with pathological complete response (p = 0.002), relapse (p = 0.028), disease-free survival (p = 0.012) and breast cancer-specific survival (p = 0.001) were also recorded. In conclusion, the relative eosinophil count and eosinophil x lymphocyte product could be promising, affordable and accessible new biomarkers that are predictive for neoadjuvant chemotherapy response and prognostic for longer survival in triplenegative and hormone receptors-negative/HER2-positive breast cancers. Confirmation of these results in a larger patient population is needed. [less ▲]

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See detailPredictive and prognostic role of peripheral blood eosinophil count in triple negative and hormone receptor negative/HER2 positive breast cancers patients undergoing neoadjuvant treatment.
ONESTI, Concetta Elisa ULiege; JOSSE, Claire ULiege; PONCIN, Aurélie ULiege et al

Scientific conference (2018, September 13)

Introduction: In clinical practices, up to 27% of breast cancer (BC) patients receive neoadjuvant chemotherapy (NAC). In this context, a pathological complete response (pCR) is the most commonly used end ... [more ▼]

Introduction: In clinical practices, up to 27% of breast cancer (BC) patients receive neoadjuvant chemotherapy (NAC). In this context, a pathological complete response (pCR) is the most commonly used end-point. High pCR rate is frequently associated with tumor infiltrating lymphocytes. Besides, circulating immune cells are also often linked to chemotherapy response. Materials and methods: We performed a retrospective analysis on 112 BC patients (79 triple negative, 33 HR-/HER2+), treated with standard NAC. The median follow-up was 37.5 months (range 9-156). Eosinophil and lymphocyte count were collected at baseline, after surgery, at 1 year of follow-up and at relapse. The primary end-point is the association between the relative eosinophil count (REC) and pCR. The secondary end-points are the associations of REC, relative lymphocyte count (RLC) and eosinophil/lymphocyte product (ELP) with relapse, disease free (DFS) and breast cancer specific (BCSS) survival and to study the variation of REC and RLC during follow-up. Results: We observed a higher pCR rate in patients with REC≥1.5% vs patients with REC <1.5% (55.6% vs 36.2%, p = 0.04), and a higher median REC in patients with pCR (1.9% vs 1.2%, p 0.042). No statistically significant associations were detected with relapse, nor between RLC with pCR or relapse. We observed a 3-year BCSS of 91% vs 80% for high and low REC respectively (p 0.05; HR 0.336, 95% CI 0.107-1.058) and of 88% vs 49% in RLC≥17.5% and <17.5% respectively (p 0.01; HR 0.217, 95% CI 0.060-0.783). No significant differences were detected for DFS. Combining the two parameters in the ELP, we observed an association with pCR (59.6% in ELP≥35.8 vs 30.9% in ELP<35.8, p 0.002), relapse (12.3% vs 29.1% in high and low ELP, p 0.028), DFS (3-year DFS 90% vs 69% in high and low ELP, p 0.012; HR 0.337, 95% CI 0.138-0.823) and BCSS (3-year BCSS 95% vs 75% in high and low ELP, p 0.001; HR 0.129, 95% CI 0.029-0.573). Moreover, we observed a raise of REC after surgery from 1.4% to 2.6% (p 0.0001) and a significant reduction at relapse from 2.8% to 1.7% (p 0.021). Conversely, a reduction of RLC from 26.9% at baseline to 20.45% after surgery (p 0.0001), without significant variation at relapse, was detected. Conclusion: REC, RLC and ELP could be new promising, affordable and accessible biomarkers predictive for NAC response and prognostic for longer survival in TNBC and HR-/HER2+ BC. Confirmation in a larger cohort is needed. [less ▲]

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See detailVariations of circulating cardiac biomarkers during and after anthracycline-containing chemotherapy in breast cancer patients
Freres, Pierre ULiege; Bouznad, N.; Servais, Laurence ULiege et al

in BMC Cancer (2018), 18(1),

Background: Over time, the chance of cure after the diagnosis of breast cancer has been increasing, as a consequence of earlier diagnosis, improved diagnostic procedures and more effective treatment ... [more ▼]

Background: Over time, the chance of cure after the diagnosis of breast cancer has been increasing, as a consequence of earlier diagnosis, improved diagnostic procedures and more effective treatment options. However, oncologists are concerned by the risk of long term treatment side effects, including congestive heart failure (CHF). Methods: In this study, we evaluated innovative circulating cardiac biomarkers during and after anthracycline-based neoadjuvant chemotherapy (NAC) in breast cancer patients. Levels of cardiac-specific troponins T (cTnT), N-terminal natriuretic peptides (NT-proBNP), soluble ST2 (sST2) and 10 circulating microRNAs (miRNAs) were measured. Results: Under chemotherapy, we observed an elevation of cTnT and NT-proBNP levels, but also the upregulation of sST2 and of 4 CHF-related miRNAs (miR-126-3p, miR-199a-3p, miR-423-5p, miR-34a-5p). The elevations of cTnT, NT-proBNP, sST2 and CHF-related miRNAs were poorly correlated, suggesting that these molecules could provide different information. Conclusions: Circulating miRNA and sST2 are potential biomarkers of the chemotherapy-related cardiac dysfunction (CRCD). Nevertheless, further studies and long-term follow-up are needed in order to evaluate if these new markers may help to predict CRCD and to identify the patients at risk to later develop CHF. © 2018 The Author(s). [less ▲]

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See detailLeptomeningeal carcinomatosis from solid tumours : a systematic review of the literature
FRERES, Pierre ULiege; GENNIGENS, Christine ULiege; Martin, Didier ULiege et al

in Belgian Journal of Medical Oncology (2017), 11

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See detailTranscriptome wide analysis of natural antisense transcripts shows potential role in breast cancer
Wenric, Stéphane ULiege; El Guendi, Sonia; CABERG, Jean-Hubert ULiege et al

Poster (2017, May)

Non-coding RNAs (ncRNA) represent at least 1/5 of the mammalian transcript amount, and about 90% of the genome length is actively transcribed. Many ncRNAs have been demonstrated to play a role in cancer ... [more ▼]

Non-coding RNAs (ncRNA) represent at least 1/5 of the mammalian transcript amount, and about 90% of the genome length is actively transcribed. Many ncRNAs have been demonstrated to play a role in cancer. Among them, natural antisense transcripts (NAT) are RNA sequences which are complementary and overlapping to those of protein-coding transcripts (PCT). NATs were punctually described as regulating gene expression, and are expected to act more frequently in cis than other ncRNAs that commonly function in trans. In this work, 22 breast cancers expressing estrogen receptors and their paired healthy tissues were analyzed by strand-specific RNA sequencing. To highlight the potential role of NATs in gene regulations occurring in breast cancer, three different gene extraction methods were used: differential expression analysis of NATs between tumor and healthy tissues, differential correlation analysis of paired NAT/PCT between tumor and healthy tissues, and NAT/PCT read count ratio variation between tumor and healthy tissues. Each of these methods yielded lists of NAT/PCT pairs that were demonstrated to be enriched in survival-associated genes on an independent cohort (TCGA). This work allows to highlight NAT lists that display a strong potential to affect the expression of genes involved in the breast cancer pathology. [less ▲]

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See detailTranscriptome-wide analysis of natural antisense transcripts shows their potential role in breast cancer.
Wenric, Stéphane ULiege; ElGuendi, Sonia; CABERG, Jean-Hubert ULiege et al

in Scientific Reports (2017), 7(1), 17452

Non-coding RNAs (ncRNA) represent 1/5 of the mammalian transcript number, and 90% of the genome length is transcribed. Many ncRNAs play a role in cancer. Among them, non-coding natural antisense ... [more ▼]

Non-coding RNAs (ncRNA) represent 1/5 of the mammalian transcript number, and 90% of the genome length is transcribed. Many ncRNAs play a role in cancer. Among them, non-coding natural antisense transcripts (ncNAT) are RNA sequences that are complementary and overlapping to those of either protein-coding (PCT) or non-coding transcripts. Several ncNATs were described as regulating protein coding gene expression on the same loci, and they are expected to act more frequently in cis compared to other ncRNAs that commonly function in trans. In this work, 22 breast cancers expressing estrogen receptors and their paired adjacent non-malignant tissues were analyzed by strand-specific RNA sequencing. To highlight ncNATs potentially playing a role in protein coding gene regulations that occur in breast cancer, three different data analysis methods were used: differential expression analysis of ncNATs between tumor and non-malignant tissues, differential correlation analysis of paired ncNAT/PCT between tumor and non-malignant tissues, and ncNAT/PCT read count ratio variation between tumor and non-malignant tissues. Each of these methods yielded lists of ncNAT/PCT pairs that were enriched in survival-associated genes. This work highlights ncNAT lists that display potential to affect the expression of protein-coding genes involved in breast cancer pathology. [less ▲]

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See detailCyclin-dependent protein kinase inhibitors in breast cancer treatment
FRERES, Pierre ULiege; LOUSBERG, Laurence ULiege; JERUSALEM, Guy ULiege

in Belgian Journal of Medical Oncology (2016), 10(4), 132-138

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See detailLa cardiotoxicité des traitements anti-cancéreux
FRERES, Pierre ULiege; PONCIN, Aurélie ULiege; MOONEN, Marie ULiege et al

in Revue Médicale de Liège (2016), 71(9), 382-387

Les cancers sont de plus en plus fréquents et leurs traitements de plus en plus agressifs. En conséquence, les médecins se trouvent régulièrement confrontés aux effets secondaires des traitements ... [more ▼]

Les cancers sont de plus en plus fréquents et leurs traitements de plus en plus agressifs. En conséquence, les médecins se trouvent régulièrement confrontés aux effets secondaires des traitements cytotoxiques. La cardiotoxicité induite par les traitements anti-cancéreux est une complication gravissime, car elle peut être mortelle et provoque un arrêt temporaire, voire définitif, des traitements. Dans cet article, nous décrivons les mécanismes, le dépistage et la prise en charge multidisciplinaire de la cardiotoxicité des agents anti-cancéreux. [less ▲]

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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 detailBRCA1 germline mutation and glioblastoma development: report of cases
Boukerroucha, Meriem ULiege; Josse, Claire ULiege; SEGERS, Karin ULiege et al

in BMC Cancer (2015), 15

Background Germline mutations in breast cancer susceptibility gene 1 (BRCA1) increase the risk of breast and ovarian cancers. However, no association between BRCA1 germline mutation and glioblastoma ... [more ▼]

Background Germline mutations in breast cancer susceptibility gene 1 (BRCA1) increase the risk of breast and ovarian cancers. However, no association between BRCA1 germline mutation and glioblastoma malignancy has ever been highlighted. Here we report two cases of BRCA1 mutated patients who developed a glioblastoma (GBM). Cases presentation Two patients diagnosed with triple negative breast cancer (TNBC) were screened for BRCA1 germline mutation. They both carried a pathogenic mutation introducing a premature STOP codon in the exon 11 of the BRCA1 gene. Few years later, both patients developed a glioblastoma and a second breast cancer. In an attempt to clarify the role played by a mutated BRCA1 allele in the GBM development, we investigated the BRCA1 mRNA and protein expression in breast and glioblastoma tumours for both patients. The promoter methylation status of this gene was also tested by methylation specific PCR as BRCA1 expression is also known to be lost by this mechanism in some sporadic breast cancers. Conclusion Our data show that BRCA1 expression is maintained in glioblastoma at the protein and the mRNA levels, suggesting that loss of heterozygosity (LOH) did not occur in these cases. The protein expression is tenfold higher in the glioblastoma of patient 1 than in her first breast carcinoma, and twice higher in patient 2. In agreement with the high protein expression level in the GBM, BRCA1 promoter methylation was not observed in these tumours. In these two cases, despite of a BRCA1 pathogenic germline mutation, the tumour-suppressor protein expression is maintained in GBM, suggesting that the BRCA1 mutation is not instrumental for the GBM development. [less ▲]

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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 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 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 detailNeoadjuvant chemotherapy in breast cancer induces miR-34a and miR-122 expression
FRERES, Pierre ULiege; JOSSE, Claire ULiege; Bovy, Nicolas ULiege et al

in Journal of Cellular Physiology (2014)

Circulating microRNAs (miRNAs) have been extensively studied in cancer as biomarkers but little is known regarding the influence of anti-cancer drugs on their expression levels. In this article, we ... [more ▼]

Circulating microRNAs (miRNAs) have been extensively studied in cancer as biomarkers but little is known regarding the influence of anti-cancer drugs on their expression levels. In this article, we describe the modifications of circulating miRNAs profile after neoadjuvant chemotherapy (NAC) for breast cancer. The expression of 188 circulating miRNAs was assessed in the plasma of 25 patients before and after NAC by RT-qPCR. Two miRNAs, miR- 34a and miR-122, that were significantly increased after NAC, were measured in tumor tissue before and after chemotherapy in 7 patients with pathological partial response (pPR) to NAC. These 2 chemotherapy-induced miRNAs were further studied in the plasma of 22 patients with adjuvant chemotherapy (AC) as well as in 12 patients who did not receive any chemotherapy. Twenty-five plasma miRNAs were modified by NAC. Among these miRNAs, miR-34a and miR-122 were highly upregulated, notably in pPR patients with aggressive breast cancer. Furthermore, miR-34a level was elevated in the remaining tumor tissue after NAC treatment. Studying the kinetics of circulating miR-34a and miR-122 expression during NAC revealed that their levels were especially increased after anthracycline-based chemotherapy. Comparisons of the plasma miRNA profiles after NAC and AC suggested that chemotherapy-induced miRNAs originated from both tumoral and non-tumoral compartments. This study is the first to demonstrate that NAC specifically induces miRNA expression in plasma and tumor tissue, which might be involved in the anti-tumor effects of chemotherapy in breast cancer patients. [less ▲]

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See detailNeoadjuvant chemotherapy in breast cancer patients induces expression of tumor suppressor miR-34a
FRERES, Pierre ULiege

Poster (2014, May 19)

Circulating microRNAs (miRNAs) are extensively studied in cancer as biomarkers but little is known about the influence of anti-cancer drugs on their expression. In this presentation, we describe the ... [more ▼]

Circulating microRNAs (miRNAs) are extensively studied in cancer as biomarkers but little is known about the influence of anti-cancer drugs on their expression. In this presentation, we describe the modifications of circulating miRNAs profile under neoadjuvant chemotherapy (NAC) for breast cancer. [less ▲]

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See detailCirculating microRNAs as diagnostic markers in breast cancer patients and their deregulation under neoadjuvant chemotherapy
FRERES, Pierre ULiege

Poster (2014, April 24)

Breast cancer is the leading cause of death by cancer among women and there is an urgent need to improve its diagnosis and prognosis. MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression ... [more ▼]

Breast cancer is the leading cause of death by cancer among women and there is an urgent need to improve its diagnosis and prognosis. MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression and many have been implicated in breast cancer. In this article, we focus on circulating miRNAs as biomarkers for breast cancers and we describe the deregulation of their expression during neoadjuvant chemotherapy (NAC). [less ▲]

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See detailA miRNA expression based diagnostic tool for breast cancer using random forests
Wenric, Stéphane ULiege; Freres, Pierre ULiege; Josse, Claire ULiege et al

Poster (2013, December 09)

We developed a novel diagnostic tool for breast cancer using circulating miRNA expression levels as features of a supervised machine learning problem. We showed very good results on an independent ... [more ▼]

We developed a novel diagnostic tool for breast cancer using circulating miRNA expression levels as features of a supervised machine learning problem. We showed very good results on an independent validation cohort. [less ▲]

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