CLCC Francois Baclesse

Caen, France

CLCC Francois Baclesse

Caen, France
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Castera L.,CLCC Francois Baclesse | Castera L.,French Institute of Health and Medical Research | Krieger S.,CLCC Francois Baclesse | Krieger S.,French Institute of Health and Medical Research | And 24 more authors.
European Journal of Human Genetics | Year: 2014

To optimize the molecular diagnosis of hereditary breast and ovarian cancer (HBOC), we developed a next-generation sequencing (NGS)-based screening based on the capture of a panel of genes involved, or suspected to be involved in HBOC, on pooling of indexed DNA and on paired-end sequencing in an Illumina GAIIx platform, followed by confirmation by Sanger sequencing or MLPA/QMPSF. The bioinformatic pipeline included CASAVA, NextGENe, CNVseq and Alamut-HT. We validated this procedure by the analysis of 59 patients' DNAs harbouring SNVs, indels or large genomic rearrangements of BRCA1 or BRCA2. We also conducted a blind study in 168 patients comparing NGS versus Sanger sequencing or MLPA analyses of BRCA1 and BRCA2. All mutations detected by conventional procedures were detected by NGS. We then screened, using three different versions of the capture set, a large series of 708 consecutive patients. We detected in these patients 69 germline deleterious alterations within BRCA1 and BRCA2, and 4 TP53 mutations in 468 patients also tested for this gene. We also found 36 variations inducing either a premature codon stop or a splicing defect among other genes: 5/708 in CHEK2, 3/708 in RAD51C, 1/708 in RAD50, 7/708 in PALB2, 3/708 in MRE11A, 5/708 in ATM, 3/708 in NBS1, 1/708 in CDH1, 3/468 in MSH2, 2/468 in PMS2, 1/708 in BARD1, 1/468 in PMS1 and 1/468 in MLH3. These results demonstrate the efficiency of NGS in performing molecular diagnosis of HBOC. Detection of mutations within other genes than BRCA1 and BRCA2 highlights the genetic heterogeneity of HBOC. © 2014 Macmillan Publishers Limited All rights reserved.


PubMed | University of Rouen, University Hospital, University of Caen Lower Normandy, Jacques Monod Hospital and 2 more.
Type: Journal Article | Journal: European journal of human genetics : EJHG | Year: 2014

To optimize the molecular diagnosis of hereditary breast and ovarian cancer (HBOC), we developed a next-generation sequencing (NGS)-based screening based on the capture of a panel of genes involved, or suspected to be involved in HBOC, on pooling of indexed DNA and on paired-end sequencing in an Illumina GAIIx platform, followed by confirmation by Sanger sequencing or MLPA/QMPSF. The bioinformatic pipeline included CASAVA, NextGENe, CNVseq and Alamut-HT. We validated this procedure by the analysis of 59 patients DNAs harbouring SNVs, indels or large genomic rearrangements of BRCA1 or BRCA2. We also conducted a blind study in 168 patients comparing NGS versus Sanger sequencing or MLPA analyses of BRCA1 and BRCA2. All mutations detected by conventional procedures were detected by NGS. We then screened, using three different versions of the capture set, a large series of 708 consecutive patients. We detected in these patients 69 germline deleterious alterations within BRCA1 and BRCA2, and 4 TP53 mutations in 468 patients also tested for this gene. We also found 36 variations inducing either a premature codon stop or a splicing defect among other genes: 5/708 in CHEK2, 3/708 in RAD51C, 1/708 in RAD50, 7/708 in PALB2, 3/708 in MRE11A, 5/708 in ATM, 3/708 in NBS1, 1/708 in CDH1, 3/468 in MSH2, 2/468 in PMS2, 1/708 in BARD1, 1/468 in PMS1 and 1/468 in MLH3. These results demonstrate the efficiency of NGS in performing molecular diagnosis of HBOC. Detection of mutations within other genes than BRCA1 and BRCA2 highlights the genetic heterogeneity of HBOC.


Demiselle J.,CLCC Francois Baclesse | Lheureux S.,CLCC Francois Baclesse | Clarisse B.,CLCC Francois Baclesse | Sevin E.,CLCC Francois Baclesse | And 2 more authors.
Bulletin du Cancer | Year: 2011

Antiangiogenic therapies have led to substantial progress in the management of kidney cancer, highly vascular tumor, and chemoresistant. These molecules have improved the prognosis of metastatic renal cancer. However, only a few isolated cases of complete response have been described and the evolution of these patients after treatment discontinuation remains unclear. From a series of patients treated for kidney cancer with anti-angiogenic in first line, the purpose of this study was to identify patients in complete response in whom treatment had been interrupted. Complete response was defined according to RECIST criteria and data were collected retrospectively at the Centre François Baclesse - Caen. Five patients were identified in complete response with a treatment discontinuation among sixty-seven patients. These five patients of good or intermediate prognosis received an initial nephrectomy followed by a first-line treatment by Sunitinib (ten cycles on average). After one year of stopping treatment, two patients are still in complete response and three patients relapsed at three, 12 and 15 months. The treatment of relapsing disease was surgical followed by monitoring or resumption of sunitinib resulting in new complete response for the all three patients. The interruption of antiangiogenic treatment seems acceptable after a complete response. ©John Libbey Eurotext.


Lheureux S.,CLCC Francois Baclesse | Joly F.,CLCC Francois Baclesse | Joly F.,University of Caen Lower Normandy
Bulletin du Cancer | Year: 2012

The management of patients with metastatic castration-resistant prostate cancer is a real challenge. Indeed, after a first line chemotherapy with docetaxel, there was no standard because the treatments were ineffective. Today, several therapeutic options are available with the development of new therapies. Among them, cabazitaxel, semisynthetic derivative of a natural taxoid, has been developed to its low recognition by the MDR system and power distribution including brain. This new chemotherapy was assessed in patients with metastatic castration-resistant prostate cancer whose disease has progressed during or after docetaxel-based therapy. Treatment with cabazitaxel plus prednisone has improved overall survival of 2.4 months compared to mitoxantrone in the TROPIC phase III. However, hematologic toxicity may be limiting with a risk of febrile neutropenia; hematopoietic growth factors are advised in case of significant neutropenia. The cabazitaxel, Jevtana®, has been approved in second line after docetaxel. Its position in relation to new types of hormone therapy, as abiraterone acetate, in the same indication requires further investigations, including predictive factors of response. Studies are on going in first line indication (compared to docetaxel) and associated to other new hormone therapies. ©John Libbey Eurotext.


Lheureux S.,CLCC Francois Baclesse | Joly F.,CLCC Francois Baclesse | Joly F.,Caen University Hospital Center
Bulletin du Cancer | Year: 2012

Endometrial cancer is the most common gynaecological cancer in western countries. Radiotherapy remains the mainstay of postoperative management, but accumulating data show that adjuvant chemotherapy may display promising results after surgery. Characteristic features of the patients and disease, type of treatment including modality of surgery, radiation and chemotherapy are different from studies reported. The results from these trials are inconsistent but certain groups of patients with high-risk features could have advantage to adjuvant chemotherapy. The indication of adjuvant chemotherapy must be discussed in this situation taking into account the patient's profile with potential comorbidities and risk of toxicities. ©John Libbey Eurotext.


Lheureux S.,CLCC Francois Baclesse | Lheureux S.,University of Caen Lower Normandy | Le Moulec S.,HIA du Val de Grace
Bulletin du Cancer | Year: 2011

Apoptosis is a programmed cellular death, a fast process (between four and six hours) in answer to a cellular stress. It involves a sequence of genetically determined intracellular events, allowing the inhibition of the main functions of the cell and its elimination by phagocytosis. The apoptosis inactivation is implied in tumours carcinogenesis. Although the tumour physiopathology implies a defect in activation-induced cell death, the treatment is designed to kill the transformed cells. The aim of this review is to describe the apoptotic mechanisms and to explain the interest of new therapeutic tools targeting apoptosis. Apoptosis is an orderly and synchronized process, regulated by two different pathways, the intrinsic way (mitochondrial) and extrinsic one (the death receptor). The targeting of apoptosis, a pathway intrinsically deficient in the tumor cells, is a potentially interesting strategy when the mechanism of its inhibition is well-identified. Small molecules targeting B-cell leukemia/lymphoma-2 (Bcl-2), inhibitor of apoptosis protein (IAPs) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors are currently under phase I/II studies, which show preliminary efficacy and safety. Their association with standard treatments seems an interesting therapeutic way in order to obtain a synergistic effect on tumor cell death. ©John Libbey Eurotext.


Machavoine J.-L.,CLCC Francois Baclesse | Machavoine J.-L.,Center hospitalier Jacques Monod | Saltel P.,CLCC Leon Berard
Psycho-Oncologie | Year: 2015

The General States of Cancer patients were conducted in France by the National League against Cancer, in 1998, 2000 and 2004; with the strong demand of being listened was renewed the specific dimension of the psychological care in oncology. The efforts of the French Psycho-Oncology Society were then recognized to find a new identity for the first psychologists and psychiatrists engaged in this field. With their professional practices being influenced by the new technologies and the organization of the modern oncology, psycho-oncologists owed answers to renewed expectations of patients close relations, and also, increasingly to caregivers and new jobs. In psychotherapy practice, they implemented many of their tools from applied psychoanalysis. They became audacious experimentalists who often had to share them in a psychology context of pluridisplinarity. Concepts and practices resulting from other clinical fields could sometimes be useful to their exercise, in collaboration with other actors in oncology. © 2015, Springer-Verlag France.


PubMed | CLCC Francois Baclesse
Type: Journal Article | Journal: Bulletin du cancer | Year: 2011

Apoptosis is a programmed cellular death, a fast process (between four and six hours) in answer to a cellular stress. It involves a sequence of genetically determined intracellular events, allowing the inhibition of the main functions of the cell and its elimination by phagocytosis. The apoptosis inactivation is implied in tumours carcinogenesis. Although the tumour physiopathology implies a defect in activation-induced cell death, the treatment is designed to kill the transformed cells. The aim of this review is to describe the apoptotic mechanisms and to explain the interest of new therapeutic tools targeting apoptosis. Apoptosis is an orderly and synchronized process, regulated by two different pathways, the intrinsic way (mitochondrial) and extrinsic one (the death receptor). The targeting of apoptosis, a pathway intrinsically deficient in the tumor cells, is a potentially interesting strategy when the mechanism of its inhibition is well-identified. Small molecules targeting B-cell leukemia/lymphoma-2 (Bcl-2), inhibitor of apoptosis protein (IAPs) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors are currently under phaseI/II studies, which show preliminary efficacy and safety. Their association with standard treatments seems an interesting therapeutic way in order to obtain a synergistic effect on tumor cell death.


PubMed | CLCC Francois Baclesse
Type: Journal Article | Journal: Bulletin du cancer | Year: 2012

The management of patients with metastatic castration-resistant prostate cancer is a real challenge. Indeed, after a first line chemotherapy with docetaxel, there was no standard because the treatments were ineffective. Today, several therapeutic options are available with the development of new therapies. Among them, cabazitaxel, semi-synthetic derivative of a natural taxoid, has been developed to its low recognition by the MDR system and power distribution including brain. This new chemotherapy was assessed in patients with metastatic castration-resistant prostate cancer whose disease has progressed during or after docetaxel-based therapy. Treatment with cabazitaxel plus prednisone has improved overall survival of 2.4months compared to mitoxantrone in the TROPIC phase III. However, hematologic toxicity may be limiting with a risk of febrile neutropenia; hematopoietic growth factors are advised in case of significant neutropenia. The cabazitaxel, Jevtana(), has been approved in second line after docetaxel. Its position in relation to new types of hormone therapy, as abiraterone acetate, in the same indication requires further investigations, including predictive factors of response. Studies are on going in first line indication (compared to docetaxel) and associated to other new hormone therapies.


PubMed | CLCC Francois Baclesse
Type: Journal Article | Journal: Bulletin du cancer | Year: 2012

Endometrial cancer is the most common gynaecological cancer in western countries. Radiotherapy remains the mainstay of postoperative management, but accumulating data show that adjuvant chemotherapy may display promising results after surgery. Characteristic features of the patients and disease, type of treatment including modality of surgery, radiation and chemotherapy are different from studies reported. The results from these trials are inconsistent but certain groups of patients with high-risk features could have advantage to adjuvant chemotherapy. The indication of adjuvant chemotherapy must be discussed in this situation taking into account the patients profile with potential comorbidities and risk of toxicities.

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