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Patrice Viens

Publications and source records attributed to Patrice Viens.

At least 19 recordsLinked to original sources
PubMed2006

Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial.

PURPOSE: The PACS 01 trial compared six cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) with a sequential regimen of three cycles of FEC followed by three cycles of docetaxel (FEC-D) as adjuvant treatment for women with node-positive early breast cancer. PATIENTS AND METHODS: Between June 1997 and March 2000, 1,999 patients with operable node-positive breast cancer were randomly assigned to either FEC every 21 days for six cycles, or three cycles of FEC followed by three cycles of docetaxel, both given every 21 days. Hormone-receptor-positive patients received tamoxifen for 5 years after chemotherapy. The primary end point was 5-year disease-free survival (DFS). RESULTS: Median follow-up was 60 months. Five-year DFS rates were 73.2% with FEC and 78.4% with FEC-D (unadjusted P = .011; adjusted P = .012). Multivariate analysis adjusted for prognostic factors showed an 18% reduction in the relative risk of relapse with FEC-D. Five-year overall survival rates were 86.7% with FEC and 90.7% with FEC-D, demonstrating a 27% reduction in the relative risk of death (unadjusted P = .014; adjusted P = .017). The incidence of grade 3 to 4 neutropenia, the need for hematopoietic growth factor, and incidence of nausea/vomiting were higher with FEC. Docetaxel was associated with more febrile neutropenia in the fourth cycle, stomatitis, edema, and nail disorders. Though rare overall, there were fewer cardiac events after FEC-D (P = .03), attributable mainly to the lower anthracycline cumulative dose. CONCLUSION: Sequential adjuvant chemotherapy with FEC followed by docetaxel significantly improves disease-free and overall survival in node-positive breast cancer patients and has a favorable safety profile.

Adult↗
PubMed2006

Frequency, prognostic impact, and subtype association of 8p12, 8q24, 11q13, 12p13, 17q12, and 20q13 amplifications in breast cancers.

BACKGROUND: Oncogene amplification and overexpression occur in tumor cells. Amplification status may provide diagnostic and prognostic information and may lead to new treatment strategies. Chromosomal regions 8p12, 8q24, 11q13, 17q12 and 20q13 are recurrently amplified in breast cancers. METHODS: To assess the frequencies and clinical impact of amplifications, we analyzed 547 invasive breast tumors organized in a tissue microarray (TMA) by fluorescence in situ hybridization (FISH) and calculated correlations with histoclinical features and prognosis. BAC probes were designed for: (i) two 8p12 subregions centered on RAB11FIP1 and FGFR1 loci, respectively; (ii) 11q13 region centered on CCND1; (iii) 12p13 region spanning NOL1; and (iv) three 20q13 subregions centered on MYBL2, ZNF217 and AURKA, respectively. Regions 8q24 and 17q12 were analyzed with MYC and ERBB2 commercial probes, respectively. RESULTS: We observed amplification of 8p12 (amplified at RAB11FIP1 and/or FGFR1) in 22.8%, 8q24 in 6.1%, 11q13 in 19.6%, 12p13 in 4.1%, 17q12 in 9.9%, 20q13Z (amplified at ZNF217 only) in 9.9%, and 20q13Co (co-amplification of two or three 20q13 loci) in 8.5% of cases. The 8q24, 12p13, and 17q12 amplifications were correlated with high grade. The most frequent single amplifications were 8p12 (9.8%), 8q24 (3.3%) and 12p13 (3.3%), 20q13Z and 20q13Co (1.6%) regions. The 17q12 and 11q13 regions were never found amplified alone. The most frequent co-amplification was 8p12/11q13. Amplifications of 8p12 and 17q12 were associated with poor outcome. Amplification of 12p13 was associated with basal molecular subtype. CONCLUSION: Our results establish the frequencies, prognostic impacts and subtype associations of various amplifications and co-amplifications in breast cancers.

Adult↗
PubMed2006

Prognosis and gene expression profiling of 20q13-amplified breast cancers.

PURPOSE: Amplification of chromosomal region 20q13 occurs in breast cancer but remains poorly characterized. EXPERIMENTAL DESIGN: To establish the frequency of 20q13 amplification and select the amplified cases to be studied, we used fluorescence in situ hybridization of bacterial artificial chromosome probes for three 20q13 loci (MYBL2, STK6, ZNF217) on sections of tissue microarrays containing 466 primary carcinoma samples. We used Affymetryx whole-genome DNA microarrays to establish the gene expression profiles of 20q13-amplified tumors and quantitative reverse transcription-PCR to validate the results. RESULTS: We found 36 (8%) 20q13-amplified samples. They were distributed in two types: type 1 tumors showed ZNF217 amplification only, whereas type 2 tumors showed amplification at two or three loci. Examination of the histoclinical features of the amplified tumors showed two strikingly opposite data. First, type 1 tumors were more frequently lymph node-negative tumors but were paradoxically associated with a poor prognosis. Second, type 2 tumors were more frequently lymph node-positive tumors but were paradoxically associated with a good prognosis. Type 1 and type 2 showed different gene expression profiles. No 20q13 gene could be associated with type 1 amplification, whereas several 20q13 genes were overexpressed in type 2 tumors. CONCLUSIONS: Our results suggest that amplified tumors of types 1 and 2 are two distinct entities resulting from two different mechanisms and associated to different prognosis.

Breast Neoplasms↗
PubMed2006

Gene expression profiling shows medullary breast cancer is a subgroup of basal breast cancers.

Medullary breast cancer (MBC) is a rare but enigmatic pathologic type of breast cancer. Despite features of aggressiveness, MBC is associated with a favorable prognosis. Morphologic diagnosis remains difficult in many cases. Very little is known about the molecular alterations involved in MBC. Notably, it is not clear whether MBC and ductal breast cancer (DBC) represent molecularly distinct entities and what genes/proteins might account for their differences. Using whole-genome oligonucleotide microarrays, we compared gene expression profiles of 22 MBCs and 44 grade III DBCs. We show that MBCs are less heterogeneous than DBCs. Whereas different molecular subtypes (luminal A, luminal B, basal, ERBB2-overexpressing, and normal-like) exist in DBCs, 95% MBCs display a basal profile, similar to that of basal DBCs. Supervised analysis identified gene expression signatures that discriminated MBCs from DBCs. Discriminator genes are associated with various cellular processes related to MBC features, in particular immune reaction and apoptosis. As compared with MBCs, basal DBCs overexpress genes involved in smooth muscle cell differentiation, suggesting that MBCs are a distinct subgroup of basal breast cancer with limited myoepithelial differentiation. Finally, MBCs overexpress a series of genes located on the 12p13 and 6p21 chromosomal regions known to contain pluripotency genes. Our results contribute to a better understanding of MBC and of mammary oncogenesis in general.

Adult↗
PubMed2006

Residual pelvic lymph node involvement after concomitant chemoradiation for locally advanced cervical cancer.

OBJECTIVE: Concomitant chemoradiation (and brachytherapy) has become the standard treatment for locally advanced cervical cancers (FIGO stage IB2 to IVA). Adjuvant surgery is optional. The aim of this study was to evaluate the rate of residual positive pelvic lymph nodes after chemoradiation. METHODS: From February 1988 to August 2004, 113 patients with locally advanced cervical cancer have been treated by chemoradiation followed by an adjuvant surgery with a pelvic lymphadenectomy performed (study group). A para-aortic lymphadenectomy had also been performed in 85 of them. RESULTS: The mean age of the patients was 48.4 years (27-74). FIGO stage was: IB2 in 17.7% (20/113), II in 44.2% (50/113), III in 21.2% (24/113) and IVA in 16.8% of the patients (19/113). The mean number of removed nodes was 11.5 (median 11) in pelvic, and 7.5 (median 7) in para-aortic basins. A pelvic lymph node involvement was present in 15.9% (18/113) of the patients after chemoradiation. In 11 patients, only one node was positive. 11.7% (10/85) of the patients had a para-aortic lymph node involvement. A residual pelvic lymph node disease has been observed in 6.3% (4/63) of the cases with no residual cervical disease (or microscopic) versus 26.5% (13/49) of the cases with macroscopic residual cervical tumor (P = 0.003). CONCLUSIONS: Our experience shows that a pelvic lymph node involvement persists in about 16% of the patients after chemoradiation. We can make the assumption that performing a pelvic lymphadenectomy along with the removal of the primary tumor after chemoradiation could reduce the rate of latero-pelvic recurrences, whatever the para-aortic lymph node status.

Adult↗
PubMed2006

Gemcitabine and epirubicin in patients with metastatic breast cancer: a phase I/II study.

Gemcitabine and epirubicin were evaluated in metastatic breast cancer (MBC) patients to determine the maximum tolerated dose (MTD), efficacy, and toxicity of the combination. Patients initially received 800 mg/m(2) of gemcitabine (days 1 and 8) and 50 mg/m(2) of epirubicin (day 1) every 21 days. Each dose level had three to eight patients. Phase II used the dose level preceding the MTD. Forty-eight patients enrolled without reaching MTD; therefore, phase II used the highest dose level (1500 mg/m(2) of gemcitabine, 90 mg/m(2) of epirubicin). After 23 patients (group A) experienced hematologic toxicities and frequent dose reductions, 15 received 1250 mg/m(2) gemcitabine (days 1 and 4) and 90 mg/m(2) epirubicin (day 1) every 21 days (group B). Out of 38 patients, 46% responded (group A 32%, group B 67%). Median response duration was 8.5 months; median time to progression 8.4 months; and median time to treatment failure 4.8 months. Gemcitabine and epirubicin are well tolerated and active in MBC patients, and the group B regimen warrants further investigation.

Adult↗
PubMed2006

Gene expression profiling and clinical outcome in breast cancer.

Pathologic and clinical heterogeneity of breast cancer reflects the poorly documented, complex, and combinatory molecular basis of the disease and is in part responsible for therapeutic failures. The DNA microarray technique allows the analysis of RNA expression of several thousands of genes simultaneously in a sample. There are multiple potential applications of the technique in cancer research. A number of recent studies have shown the promising role of gene expression profiling in breast cancer by identifying new prognostic subclasses unidentifiable by conventional parameters and new prognostic and/or predictive gene signatures, whose predictive impact is superior to conventional histoclinical prognostic factors. In this review we describe current use of DNA microarrays in the prognosis of breast cancer. We also discuss issues that need to be addressed in the near future to allow the method to reach its full potential.

Breast Neoplasms↗
PubMed2006

[G-CSF in oncology].

Neutropenia and its subsequent infectious complications represent the most common dose-limiting toxicity of cancer chemotherapy. Febrile neutropenia (FN) occurs with common chemotherapy regimens in 25 to 40 % of treatment-naive patients, and its severity depends on the dose intensity of the chemotherapy regimen, the patient's prior history and comorbidities. Neutropenia is associated with the risk of life-threatening infections as well as chemotherapy dose reductions and delays that may compromise treatment outcome. One of the first, most important and sustained applications of recombinant DNA technology in medicine was the cloning and introduction into clinical practice of several glycoprotein factors involved in the regulation of hematopoiesis. Colony-stimulating factors (CSFs) such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are now an integral part of the prevention of potentially life-threatening FN. Important uses of CSFs in oncology are prevention of FN after chemotherapy, treatment of FN, collection of CSF-mobilised peripheral stem cells and support following peripheral stem cells transplantation. This article reviews the data supporting the clearly clinical applications of CSFs in oncology.

Antineoplastic Agents↗
PubMed2005

Gene expression profiling identifies molecular subtypes of inflammatory breast cancer.

Breast cancer is a heterogeneous disease. Comprehensive gene expression profiles obtained using DNA microarrays have revealed previously indistinguishable subtypes of noninflammatory breast cancer (NIBC) related to different features of mammary epithelial biology and significantly associated with survival. Inflammatory breast cancer (IBC) is a rare, particular, and aggressive form of disease. Here we have investigated whether the five molecular subtypes described for NIBC (luminal A and B, basal, ERBB2 overexpressing, and normal breast-like) were also present in IBC. We monitored the RNA expression of approximately 8,000 genes in 83 breast tissue samples including 37 IBC, 44 NIBC, and 2 normal breast samples. Hierarchical clustering identified the five subtypes of breast cancer in both NIBC and IBC samples. These subtypes were highly similar to those defined in previous studies and associated with similar histoclinical features. The robustness of this classification was confirmed by the use of both alternative gene set and analysis method, and the results were corroborated at the protein level. Furthermore, we show that the differences in gene expression between NIBC and IBC and between IBC with and without pathologic complete response that we have recently reported persist in each subtype. Our results show that the expression signatures defining molecular subtypes of NIBC are also present in IBC. Obtained using different patient series and different microarray platforms, they reinforce confidence in the expression-based molecular taxonomy but also give evidence for its universality in breast cancer, independently of a specific clinical form.

Adenocarcinoma↗
PubMed2005

Protein expression profiling identifies subclasses of breast cancer and predicts prognosis.

Breast cancer is a heterogeneous disease whose evolution is difficult to predict by using classic histoclinical prognostic factors. Prognostic classification can benefit from molecular analyses such as large-scale expression profiling. Using immunohistochemistry on tissue microarrays, we have monitored the expression of 26 selected proteins in more than 1,600 cancer samples from 552 consecutive patients with early breast cancer. Both an unsupervised approach and a new supervised method were used to analyze these profiles. Hierarchical clustering identified relevant clusters of coexpressed proteins and clusters of tumors. We delineated protein clusters associated with the estrogen receptor and with proliferation. Tumor clusters correlated with several histoclinical features of samples, including 5-year metastasis-free survival (MFS), and with the recently proposed pathophysiologic taxonomy of disease. The supervised method identified a set of 21 proteins whose combined expression significantly correlated to MFS in a learning set of 368 patients (P < 0.0001) and in a validation set of 184 patients (P < 0.0001). Among the 552 patients, the 5-year MFS was 90% for patients classified in the "good-prognosis class" and 61% for those classified in the "poor-prognosis class" (P < 0.0001). This difference remained significant when the molecular grouping was applied according to lymph node or estrogen receptor status, as well as the type of adjuvant systemic therapy. In multivariate analysis, the 21-protein set was the strongest independent predictor of clinical outcome. These results show that protein expression profiling may be a clinically useful approach to assess breast cancer heterogeneity and prognosis in stage I, II, or III disease.

Adult↗
PubMed2005

Clinical experience with the delivery of thawed and washed autologous blood cells, with an automated closed fluid management device: CytoMate.

BACKGROUND: Washing out of thawed autologous grafts, before reinfusion in poor-prognosis cancer patients who undergo high-dose chemotherapy, is desirable. The procedure allows for the reduction of infused dimethyl sulfoxide (DMSO) quantities and the performance of biologic controls on the infused cell product. STUDY DESIGN AND METHODS: Three-hundred four patients were treated with intensified chemotherapy and autologous transplantation at a single institution. Fifty-four of them received washed cell products, because three or more bags were to be reinfused. The recently available, closed, automated, and current good manufacturing practice-compliant device (CytoMate, Baxter Oncology) was used for this purpose. RESULTS: The performances of the device were similar to previously reported results, with greater than 75 percent CD34+ cell recovery. Neutrophil and platelet (PLT) recoveries were similar in the group of patients receiving washed cells and in the group of patients for whom cell products were extemporaneously thawed at the bedside. Adverse events that are typically reported after DMSO infusion were significantly less frequent and less severe in patients who received washed cells. Finally, the nurse staff on the transplant ward reported a decreased workload and more satisfactory procedure when infusing washed cell products. CONCLUSION: The CytoMate device allows for a significant reduction in DMSO infusion, with a diminished frequency and severity of immediate side effects and does not compromise neutrophil or PLT engraftment.

Adult↗
PubMed2004

Gene expression profiling for molecular characterization of inflammatory breast cancer and prediction of response to chemotherapy.

Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer with a 5-year survival limited to approximately 40%. Diagnosis, based on clinical and/or pathological criteria, may be difficult. Optimal systemic neoadjuvant therapy and accurate predictors of pathological response have yet to be defined for increasing response rate and survival. Using DNA microarrrays containing approximately 8,000 genes, we profiled breast cancer samples from 81 patients, including 37 with IBC and 44 with noninflammatory breast cancer (NIBC). Global unsupervised hierarchical clustering was able to some extent to distinguish IBC and NIBC cases and revealed subclasses of IBC. Supervised analysis identified a 109-gene set the expression of which discriminated IBC from NIBC samples. This molecular signature was validated in an independent series of 26 samples, with an overall performance accuracy of 85%. Discriminator genes were associated with various cellular processes possibly related to the aggressiveness of IBC, including signal transduction, cell motility, adhesion, and angiogenesis. A similar approach, with leave-one-out cross-validation, identified an 85-gene set that divided IBC patients with significantly different pathological complete response rate (70% in one group and 0% in the other group). These results show the potential of gene expression profiling to contribute to a better understanding of IBC, and to provide new diagnostic and predictive factors for IBC, as well as for potential therapeutic targets.

Adult↗
PubMed2004

[What is new about sentinel lymph node biopsy in breast cancer?].

Sentinel lymph node biopsy concept was described in several reports since 1994. Technical and identification procedure, false negative risk, learning curve criteria and benefits concerning cancer stadification and postoperative morbidity were assessed. Peroperative and postoperative pathologic examination procedures are improving progressively but remains still under debate. Classification for micro-metastasis, isolated cells and macro-metastasis in sentinel lymph node was suggested but their immunohistochimic detection and prognostic impact are unclear. These parts are discussed in this article.

Axilla↗
PubMed2004

[Sentinel lymph node negative breast cancer larger than 30 mm: is axillary lymph node dissection constantly necessary?].

Benefits provided by sentinel lymph node biopsy (SLNB) include improvement of pathologic examination and lower rate of sequels. The aim of this study was to assess the accuracy of this procedure in large tumors. From march 1999 and december 2003, 663 patients were operated for a breast cancer and underwent a SLNB. All patients with tumor larger than 30 mm and/or with involved SLNB underwent a complete axillary dissection (AD). One hundred and sixteen patients (17.5%) with a tumor larger than 30 mm underwent an AD. Identification rate of SLNB was 94% (109/116). Among the 43 cases with non metastatic SLNB, the AD was negative in 39 cases (90.7%). In four cases a palpable non sentinel lymph node discovered during the SLNB procedure was found to be involved. In one case the lymphoscintigraphy found only one lymph node with a very low fixation and an AD was performed because of low efficiency of the lymphoscintigraphy procedure. SLNB false negative rate was 1.4 % (1/72) among the 72 cases with lymph node involvement. AD was performed in 66 cases (60.5%) during the same operating time than the SLNB. AD showed a lymph node involvement in 30 cases (30/72, 41.7%): in 5 cases among 24 cases with microscopic disease (20.8%) and in 25 cases among 48 cases with macroscopic disease (52%). This series results suggest than AD could be avoided for negative SLNB tumors up to 50 mm at pathologic examination in patients with clinically-measured tumor smaller than 30 mm.

Adult↗
PubMed2004

Identification and validation of an ERBB2 gene expression signature in breast cancers.

ERBB2 is a transmembrane tyrosine kinase receptor encoded by a gene located in chromosome region 17q12. Overexpression of ERBB2, generally by way of gene amplification, plays a role in mammary oncogenesis. This alteration can be overcome by use of the humanized monoclonal antibody trastuzumab (Herceptin). Accurate determination of ERBB2 status is required for appropriate use of this targeted therapy and is currently analysed by immunohistochemistry (IHC) on tissue sections and/or fluorescence in situ hybridisation (FISH) on interphase chromosomes. We have studied the gene expression profiles of a series of 213 breast tumours and 16 breast cancer cell lines with known ERBB2 status, using Ipsogen's DiscoveryChip microarrays with approximately 9000 cDNAs. We have identified 36 genes and expressed sequence tags that were differentially expressed in tumours and in cell lines with and without ERBB2 protein overexpression. This ERBB2-specific gene expression signature (GES) contained 29 overexpressed genes including the ERBB2 gene itself, five genes located in its immediate vicinity on 17q12, non-17q genes such as GATA4 and eight downregulated genes including oestrogen receptor alpha (ER). Some correlations were validated at the protein level using IHC on tissue microarrays. The GES was able to distinguish ERBB2-negative and -positive cancer samples, as well as FISH-negative and FISH-positive ERBB2 2+ IHC samples.

Adult↗
PubMed2004

Gene expression profiling of colon cancer by DNA microarrays and correlation with histoclinical parameters.

Different diagnostic and prognostic groups of colorectal carcinoma (CRC) have been defined. However, accurate diagnosis and prediction of survival are sometimes difficult. Gene expression profiling might improve these classifications and bring new insights into underlying molecular mechanisms. We profiled 50 cancerous and noncancerous colon tissues using DNA microarrrays consisting of approximately 8000 spotted human cDNA. Global hierarchical clustering was to some extent able to distinguish clinically relevant subgroups, normal versus cancer tissues and metastatic versus nonmetastatic tumours. Supervised analyses improved these segregations by identifying sets of genes that discriminated between normal and tumour tissues, tumours associated or not with lymph node invasion or genetic instability, and tumours from the right or left colon. A similar approach identified a gene set that divided patients with significantly different 5-year survival (100% in one group and 40% in the other group; P=0.005). Discriminator genes were associated with various cellular processes. An immunohistochemical study on 382 tumour and normal samples deposited onto a tissue microarray subsequently validated the upregulation of NM23 in CRC and a downregulation in poor prognosis tumours. These results suggest that microarrays may provide means to improve the classification of CRC, provide new potential targets against carcinogenesis and new diagnostic and/or prognostic markers and therapeutic targets.

Colon↗
PubMed2004

Immunophenotypic analysis of inflammatory breast cancers: identification of an 'inflammatory signature'.

Inflammatory breast cancer (IBC) is a rare but very aggressive form of breast cancer. Its definition is based on clinical criteria, but a molecular definition could be useful when data are incomplete or features are missing. Recently, the identification of overexpression of E-cadherin in IBC has improved understanding of the molecular basis of this disease. Consequently, the aim of this study was to try to determine an immunophenotypic 'signature' of IBC. A series of 80 cases of IBC were compared with 552 non-IBC control cases and a model was elaborated to evaluate the probability of an inflammatory carcinoma being present in any clinical situation. Tissue microarrays (TMAs) were used to determine the immunohistochemical profile of eight proteins including E-cadherin, EGFR, oestrogen and progesterone receptor (ER and PR), MIB1, ERBB2, MUC1, and P53. All the parameters tested were differentially expressed between IBC and control cases in univariate analysis (p < 0.001). The five variables that were significantly associated with IBC in multivariate analysis were E-cadherin > or = 300 [HR = 5.64 (2.92-10.87)], ER negative [HR = 3.00 (1.67-5.51)], MIB1 > 20 [HR = 3.54 (1.87-6.71)], MUC1 cytoplasmic staining [HR = 2.72 (1.49-4.96)], and ERBB2 positive 2+ or 3+ [HR = 2.46 (1.26-4.78)]. The probability that a breast cancer with this full phenotype at diagnosis was an IBC was 90.5%. If any one of the five parameters was missing, this probability dropped to 75% and was less than 50% when one, two, or three parameters were present. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) of patients with IBC were not significantly different from those of the non-IBC control group that expressed four or five parameters (nIBC-1), but this nIBC-1 control group had a significantly worse outcome than the non-IBC control group (nIBC-2) with only 0-3 parameters (p = 0.0049 for OS and p < 0.0001 for DFS). In conclusion, an immunophenotypic signature was suggested for IBC. This could help to determine the worst cases, independent of clinical criteria.

Adult↗