17 results on '"Finetti, Pascal"'
Search Results
2. Inflammatory breast cancer cells are characterized by abrogated TGFβ1-dependent cell motility and SMAD3 activity
- Author
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Rypens, Charlotte, Marsan, Melike, Van Berckelaer, Christophe, Billiet, Charlotte, Melis, Kirsten, Lopez, Sara Perez, van Dam, Peter, Devi, Gayathri R., Finetti, Pascal, Ueno, Naoto T., Bertucci, François, Dirix, Piet, Neven, Patrick, Vermeulen, Peter, Dirix, Luc, and Van Laere, Steven J.
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- 2020
- Full Text
- View/download PDF
3. Microarray Analysis Identifies an Expression Signature for Inflammatory Breast Cancer
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Bertucci, François, Finetti, Pascal, Chaffanet, Max, Viens, Patrice, Birnbaum, Daniel, Ueno, Naoto T., editor, and Cristofanilli, Massimo, editor
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- 2012
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4. HDAC6 activity is a non-oncogene addiction hub for inflammatory breast cancers
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Putcha, Preeti, Yu, Jiyang, Rodriguez-Barrueco, Ruth, Saucedo-Cuevas, Laura, Villagrasa, Patricia, Murga-Penas, Eva, Quayle, Steven N., Yang, Min, Castro, Veronica, Llobet-Navas, David, Birnbaum, Daniel, Finetti, Pascal, Woodward, Wendy A., Bertucci, François, Alpaugh, Mary L., Califano, Andrea, and Silva, Jose
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- 2015
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5. MARCKS as a Potential Therapeutic Target in Inflammatory Breast Cancer.
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Manai, Maroua, ELBini-Dhouib, Ines, Finetti, Pascal, Bichiou, Haifa, Reduzzi, Carolina, Aissaoui, Dorra, Ben-Hamida, Naziha, Agavnian, Emilie, Srairi-Abid, Najet, Lopez, Marc, Amri, Fatma, Guizani-Tabbane, Lamia, Rahal, Khaled, Mrad, Karima, Manai, Mohamed, Birnbaum, Daniel, Mamessier, Emilie, Cristofanilli, Massimo, Boussen, Hamouda, and Kharrat, Maher
- Subjects
PTEN protein ,BREAST cancer ,PEPTIDES ,BIOMARKERS ,PI3K/AKT pathway ,CANCER cells ,CANCER stem cells - Abstract
Inflammatory breast cancer (IBC) is the most pro-metastatic form of breast cancer (BC). We previously demonstrated that protein overexpression of Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) protein was associated with shorter survival in IBC patients. MARCKS has been associated with the PI3K/AKT pathway. MARCKS inhibitors are in development. Our objective was to investigate MARCKS, expressed preferentially in IBC that non-IBC (nIBC), as a novel potential therapeutic target for IBC. The biologic activity of MPS, a MARCKS peptide inhibitor, on cell proliferation, migration, invasion, and mammosphere formation was evaluated in IBC (SUM149 and SUM190) and nIBC (MDA-MB-231 and MCF7) cell lines, as well as its effects on protein expression in the PTEN/AKT and MAPK pathways. The prognostic relevance of MARCKS and phosphatase and tensin homolog (PTEN) protein expression as a surrogate marker of metastasis-free survival (MFS) was evaluated by immunohistochemistry (IHC) in a retrospective series of archival tumor samples derived from 180 IBC patients and 355 nIBC patients. In vitro MPS impaired cell proliferation, migration and invasion, and mammosphere formation in IBC cells. MARCKS inhibition upregulated PTEN and downregulated pAKT and pMAPK expression in IBC cells, but not in nIBC cells. By IHC, MARCKS expression and PTEN expression were negatively correlated in IBC samples and were associated with shorter MFS and longer MFS, respectively, in multivariate analysis. The combination of MARCKS-/PTEN+ protein status was associated with longer MFS in IBC patient only (p = 8.7 × 10
−3 ), and mirrored the molecular profile (MARCKS-downregulated/PTEN-upregulated) of MPS-treated IBC cell lines. In conclusion, our results uncover a functional role of MARCKS implicated in IBC aggressiveness. Associated with the good-prognosis value of the MARCKS-/PTEN+ protein status that mirrors the molecular profile of MPS-treated IBC cell lines, our results suggest that MARCKS could be a potential therapeutic target in patients with MARCKS-positive IBC. Future preclinical studies using a larger panel of IBC cell lines, animal models and analysis of a larger series of clinical samples are warranted in order to validate our results. [ABSTRACT FROM AUTHOR]- Published
- 2022
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6. Lipocalin 2 promotes inflammatory breast cancer tumorigenesis and skin invasion.
- Author
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Villodre, Emilly S., Xiaoding Hu, Larson, Richard, Finetti, Pascal, Gomez, Kristen, Balema, Wintana, Stecklein, Shane R., Santiago-Sanchez, Ginette, Krishnamurthy, Savitri, Juhee Song, Xiaoping Su, Ueno, Naoto T., Tripathy, Debu, Van Laere, Steven, Bertucci, François, Vivas-Mejía, Pablo, Woodward, Wendy A., and Debeb, Bisrat G.
- Abstract
Inflammatory breast cancer (IBC) is an aggressive form of primary breast cancer characterized by rapid onset and high risk of metastasis and poor clinical outcomes. The biological basis for the aggressiveness of IBC is still not well understood and no IBC-specific targeted therapies exist. In this study, we report that lipocalin 2 (LCN2), a small secreted glycoprotein belonging to the lipocalin superfamily, is expressed at significantly higher levels in IBC vs non-IBC tumors, independently of molecular subtype. LCN2 levels were also significantly higher in IBC cell lines and in their culture media than in non-IBC cell lines. High expression was associated with poor-prognosis features and shorter overall survival in IBC patients. Depletion of LCN2 in IBC cell lines reduced colony formation, migration, and cancer stem cell populations in vitro and inhibited tumor growth, skin invasion, and brain metastasis in mouse models of IBC. Analysis of our proteomics data showed reduced expression of proteins involved in cell cycle and DNA repair in LCN2-silenced IBC cells. Our findings support that LCN2 promotes IBC tumor aggressiveness and offer a new potential therapeutic target for IBC. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Inflammatory breast cancer in 210�patients: A retrospective study on epidemiological, anatomo‑clinical features and therapeutic results
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Manai, Maroua, Finetti, Pascal, Mejri, Nesrine, Athimni, Salma, Birnbaum, Daniel, Bertucci, François, Rahal, Khaled, Gamoudi, Amor, Chaffanet, Max, Manai, Mohamed, Boussen, Hamouda, Bidaut, Ghislain, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Abderrahmen Mami, Institut Salah Azaiez de Cancer, Université de Tunis El Manar (UTM), Inst Carcinol Salah Azaiz Tunis, Unité de Biochimie et Biologie Moléculaire, Faculté des Sciences Mathématiques, Physiques et Naturelles de Tunis (FST), Université de Tunis El Manar (UTM)-Université de Tunis El Manar (UTM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Axillary lymph nodes ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,chemotherapy response ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Inflammatory breast cancer ,Gastroenterology ,survival ,histology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Epidemiology ,medicine ,Pathological ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Neoadjuvant therapy ,business.industry ,Cancer ,Retrospective cohort study ,Articles ,medicine.disease ,3. Good health ,[SDV] Life Sciences [q-bio] ,Exact test ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,immunohistochemistry ,epidemiology ,prognosis ,business ,inflammatory breast cancer - Abstract
International audience; To report epidemiological and anatomo-clinical features within a retrospective series of inflammatory breast cancer and to evaluate prognostic factors. This retrospective study included 210 Tunisian patients presenting a clinically diagnosed IBC, treated at the Institute Salah Azaiez (ISA) of Tunis, Tunisia, from 2008 to 2013. We collected data on epidemiology, anatomo-clinical and biological features and histologic response to neoadjuvant therapy. Overall and disease-free survivals were calculated by Kaplan-Meier method and compared by log-rank tests and Cox's models were used to identify prognostic factors impacting survival. The 210 IBC patients had a median age of 42 years (24-62) and 15% of them were aged less than 35 years. Mean age at menarche was 13 years and 45% had their 1st childbirth before 23 years. On histology, grades III represented 42% of cases, hormone receptors were negative in 59%, HER2 over-expressed in 32, 25% of our IBC cases had a triple negative profile and Ki-67 was >20% in 53% of cases. High pathological grade III was significantly correlated to TN subtype (58%) (Fisher's exact test, P=7.5×10-3). Further, high Ki-67 expression (>20%) was evident in the TN subtype (84%) (Fisher's exact test, P=3.7×10-4). After neoadjuvant therapy (and trastuzumab in 88 and 69% of HER2+ patients, respectively), we observed 49% of objective clinical responses and 35% of pathological complete response (pCR) and >3 axillary lymph nodes were invaded on a resected tumor in 55% of cases. Overall survival (OS) was associated with age at menarche (Wald-test, P=2.2×10-2) and metastases at diagnosis (Wald-test, P=2.4×10-2). Reaching a pCR was correlated with a better metastasis-free survival (MFS), (Fisher's exact test, P=3.6×10-2).
- Published
- 2018
8. Immune landscape of inflammatory breast cancer suggests vulnerability to immune checkpoint inhibitors.
- Author
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Bertucci, François, Boudin, Laurys, Finetti, Pascal, Van Berckelaer, Christophe, Van Dam, Peter, Dirix, Luc, Viens, Patrice, Gonçalves, Anthony, Ueno, Naoto T., Van Laere, Steven, Birnbaum, Daniel, and Mamessier, Emilie
- Subjects
IMMUNE checkpoint inhibitors ,BREAST cancer ,IMMUNE checkpoint proteins ,GENE expression profiling ,TERTIARY structure ,MELANOMA ,IPILIMUMAB - Abstract
Background. Anti-PD1/PDL1 immune checkpoint inhibitors (ICIs) showed promising results in breast cancer, and exploration of additional actionable immune checkpoints is ongoing. Inflammatory breast cancer (IBC) is an aggressive form of disease, the immune tumor microenvironment (TME) of which is poorly known. We aimed at providing the first comprehensive immune portrait of IBCs. Methods. From the gene expression profiles of 137 IBC and 252 non-IBC clinical samples, we measured the fractions of 22 immune cell types, expression of signatures associated with tertiary lymphoid structures (TLS) and with the response to ICIs (T cell-inflamed signature: TIS) and of 18 genes coding for major actionable immune checkpoints. The IBC/non-IBC comparison was adjusted upon the clinicopathological variables. Results. The immune profiles of IBCs were heterogeneous. CIBERSORT analysis showed profiles rich in macrophages, CD8+ and CD4 + T-cells, with remarkable similarity with melanoma TME. The comparison with non-IBCs showed significant enrichment in Ml macrophages, γδ T-cells, and memory B-cells. IBCs showed higher expression of TLS and TIS signatures. The TIS signature displayed values in IBCs close to those observed in other cancers sensitive to ICIs. Two-thirds of actionable immune genes (HAVCR2/TIM3, CD27, CD70, CTLA4, ICOS, IDO1, LAG3, PDCD1, TNFRSF9, PVRIG, CD274/PDL1, and TIGIT) were overexpressed in IBCs as compared to normal breast and two-thirds were overexpressed in IBCs versus non-IBCs, with very frequent co-overexpression. For most of them, the overexpression was associated with better pathological response to chemotherapy. Conclusion. Our results suggest the potential higher vulnerability of IBC to ICIs. Clinical trials. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
9. NOTCH and DNA repair pathways are more frequently targeted by genomic alterations in inflammatory than in non‐inflammatory breast cancers.
- Author
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Bertucci, François, Rypens, Charlotte, Finetti, Pascal, Guille, Arnaud, Adélaïde, José, Monneur, Audrey, Carbuccia, Nadine, Garnier, Séverine, Dirix, Piet, Gonçalves, Anthony, Vermeulen, Peter, Debeb, Bisrat G., Wang, Xiaoping, Dirix, Luc, Ueno, Naoto T., Viens, Patrice, Cristofanilli, Massimo, Chaffanet, Max, Birnbaum, Daniel, and Van Laere, Steven
- Abstract
Inflammatory breast cancer (IBC) is the most pro‐metastatic form of breast cancer. Better understanding of its pathophysiology and identification of actionable genetic alterations (AGAs) are crucial to improve systemic treatment. We aimed to define the DNA profiles of IBC vs noninflammatory breast cancer (non‐IBC) clinical samples in terms of copy number alterations (CNAs), mutations, and AGAs. We applied targeted next‐generation sequencing (tNGS) and array‐comparative genomic hybridization (aCGH) to 57 IBC and 50 non‐IBC samples and pooled these data with four public datasets profiled using NGS and aCGH, leading to a total of 101 IBC and 2351 non‐IBC untreated primary tumors. The respective percentages of each molecular subtype [hormone receptor‐positive (HR+)/HER2−, HER2+, and triple‐negative] were 68%, 15%, and 17% in non‐IBC vs 25%, 35%, and 40% in IBC. The comparisons were adjusted for both the molecular subtypes and the American Joint Committee on Cancer (AJCC) stage. The 10 most frequently altered genes in IBCs were TP53 (63%), HER2/ERBB2 (30%), MYC (27%), PIK3CA (21%), BRCA2 (14%), CCND1 (13%), GATA3 (13%), NOTCH1 (12%), FGFR1 (11%), and ARID1A (10%). The tumor mutational burden was higher in IBC than in non‐IBC. We identified 96 genes with an alteration frequency (p < 5% and q < 20%) different between IBC and non‐IBC, independently from the molecular subtypes and AJCC stage; 95 were more frequently altered in IBC, including TP53, genes involved in the DNA repair (BRCA2) and NOTCH pathways, and one (PIK3CA) was more frequently altered in non‐IBC. Ninety‐seven percent of IBCs displayed at least one AGA. This percentage was higher than in non‐IBC (87%), notably for drugs targeting DNA repair, NOTCH signaling, and CDK4/6, whose pathways were more frequently altered (DNA repair) or activated (NOTCH and CDK4/6) in IBC than in non‐IBC. The genomic landscape of IBC is different from that of non‐IBC. Enriched AGAs in IBC may explain its aggressiveness and provide clinically relevant targets. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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10. Inflammatory breast cancer in 210 patients: A retrospective study on epidemiological, anatomo-clinical features and therapeutic results.
- Author
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Manai, Maroua, Finetti, Pascal, Mejri, Nesrine, Athimni, Salma, Birnbaum, Daniel, Bertucci, François, Rahal, Khaled, Gamoudi, Amor, Chaffanet, Max, Manai, Mohamed, and Boussen, Hamouda
- Subjects
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BREAST cancer , *HORMONE receptors , *CANCER patients , *MENARCHE , *RETROSPECTIVE studies - Abstract
To report epidemiological and anatomo-clinical features within a retrospective series of inflammatory breast cancer and to evaluate prognostic factors. This retrospective study included 210 Tunisian patients presenting a clinically diagnosed IBC, treated at the Institute Salah Azaiez (ISA) of Tunis, Tunisia, from 2008 to 2013. We collected data on epidemiology, anatomo-clinical and biological features and histologic response to neoadjuvant therapy. Overall and disease-free survivals were calculated by Kaplan-Meier method and compared by log-rank tests and Cox's models were used to identify prognostic factors impacting survival. The 210 IBC patients had a median age of 42 years (24–62) and 15% of them were aged less than 35 years. Mean age at menarche was 13 years and 45% had their 1st childbirth before 23 years. On histology, grades III represented 42% of cases, hormone receptors were negative in 59%, HER2 over-expressed in 32, 25% of our IBC cases had a triple negative profile and Ki-67 was >20% in 53% of cases. High pathological grade III was significantly correlated to TN subtype (58%) (Fisher's exact test, P=7.5×10−3). Further, high Ki-67 expression (>20%) was evident in the TN subtype (84%) (Fisher's exact test, P=3.7×10−4). After neoadjuvant therapy (and trastuzumab in 88 and 69% of HER2+ patients, respectively), we observed 49% of objective clinical responses and 35% of pathological complete response (pCR) and >3 axillary lymph nodes were invaded on a resected tumor in 55% of cases. Overall survival (OS) was associated with age at menarche (Wald-test, P=2.2×10−2) and metastases at diagnosis (Wald-test, P=2.4×10−2). Reaching a pCR was correlated with a better metastasis-free survival (MFS), (Fisher's exact test, P=3.6×10−2). [ABSTRACT FROM AUTHOR]
- Published
- 2019
11. Decreased expression of ABAT and STC2 hallmarks ER-positive inflammatory breast cancer and endocrine therapy resistance in advanced disease.
- Author
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Jansen, Maurice P.H.M., Sas, Leen, Sieuwerts, Anieta M., Van Cauwenberghe, Caroline, Ramirez-Ardila, Diana, Look, Maxime, Ruigrok-Ritstier, Kirsten, Finetti, Pascal, Bertucci, François, Timmermans, Mieke M., van Deurzen, Carolien H.M., Martens, John W.M., Simon, Iris, Roepman, Paul, Linn, Sabine C., van Dam, Peter, Kok, Marleen, Lardon, Filip, Vermeulen, Peter B., and Foekens, John A.
- Abstract
Background Patients with Estrogen Receptor α-positive (ER+) Inflammatory Breast Cancer (IBC) are less responsive to endocrine therapy compared with ER+ non-IBC (nIBC) patients. The study of ER+ IBC samples might reveal biomarkers for endocrine resistant breast cancer. Materials & methods Gene expression profiles of ER+ samples from 201 patients were explored for genes that discriminated between IBC and nIBC. Classifier genes were applied onto clinically annotated expression data from 947 patients with ER+ breast cancer and validated with RT-qPCR for 231 patients treated with first-line tamoxifen. Relationships with metastasis-free survival (MFS) and progression-free survival (PFS) following adjuvant and first-line endocrine treatment, respectively, were investigated using Cox regression analysis. Results A metagene of six genes including the genes encoding for 4-aminobutyrate aminotransferase ( ABAT ) and Stanniocalcin-2 ( STC2 ) were identified to distinguish 22 ER+ IBC from 43 ER+ nIBC patients and remained discriminatory in an independent series of 136 patients. The metagene and two genes were not prognostic in 517 (neo)adjuvant untreated lymph node-negative ER+ nIBC breast cancer patients. Only ABAT was related to outcome in 250 patients treated with adjuvant tamoxifen. Three independent series of in total 411 patients with advanced disease showed increased metagene scores and decreased expression of ABAT and STC2 to be correlated with poor first-line endocrine therapy outcome. The biomarkers remained predictive for first-line tamoxifen treatment outcome in multivariate analysis including traditional factors or published signatures. In an exploratory analysis, ABAT and STC2 protein expression levels had no relation with PFS after first-line tamoxifen. Conclusions This study utilized ER+ IBC to identify a metagene including ABAT and STC2 as predictive biomarkers for endocrine therapy resistance. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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12. Systems biology analysis reveals NFAT5 as a novel biomarker and master regulator of inflammatory breast cancer.
- Author
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Remo, Andrea, Simeone, Ines, Pancione, Massimo, Parcesepe, Pietro, Finetti, Pascal, Cerulo, Luigi, Bensmail, Halima, Birnbaum, Daniel, Van Laere, Steven J., Colantuoni, Vittorio, Bonetti, Franco, Bertucci, François, Manfrin, Erminia, and Ceccarelli, Michele
- Subjects
SYSTEMS biology ,BIOMARKERS ,INFLAMMATORY breast cancer ,PHENOTYPES ,ALGORITHMS ,GENE expression ,IMMUNOHISTOCHEMISTRY - Abstract
Background: Inflammatory breast cancer (IBC) is the most rare and aggressive variant of breast cancer (BC); however, only a limited number of specific gene signatures with low generalization abilities are available and few reliable biomarkers are helpful to improve IBC classification into a molecularly distinct phenotype. We applied a network-based strategy to gain insight into master regulators (MRs) linked to IBC pathogenesis. Methods: In-silico modeling and Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) on IBC/non-IBC (nIBC) gene expression data (n = 197) was employed to identify novel master regulators connected to the IBC phenotype. Pathway enrichment analysis was used to characterize predicted targets of candidate genes. The expression pattern of the most significant MRs was then evaluated by immunohistochemistry (IHC) in two independent cohorts of IBCs (n = 39) and nIBCs (n = 82) and normal breast tissues (n = 15) spotted on tissue microarrays. The staining pattern of non-neoplastic mammary epithelial cells was used as a normal control. Results: Using in-silico modeling of network-based strategy, we identified three top enriched MRs (NFAT5, CTNNB1 or β-catenin, and MGA) strongly linked to the IBC phenotype. By IHC assays, we found that IBC patients displayed a higher number of NFAT5-positive cases than nIBC (69.2% vs. 19.5%; p-value = 2.79 10
-7 ). Accordingly, the majority of NFAT5-positive IBC samples revealed an aberrant nuclear expression in comparison with nIBC samples (70% vs. 12.5%; p-value = 0.000797). NFAT5 nuclear accumulation occurs regardless of WNT/β-catenin activated signaling in a substantial portion of IBCs, suggesting that NFAT5 pathway activation may have a relevant role in IBC pathogenesis. Accordingly, cytoplasmic NFAT5 and membranous β-catenin expression were preferentially linked to nIBC, accounting for the better prognosis of this phenotype. Conclusions: We provide evidence that NFAT-signaling pathway activation could help to identify aggressive forms of BC and potentially be a guide to assignment of phenotype-specific therapeutic agents. The NFAT5 transcription factor might be developed into routine clinical practice as a putative biomarker of IBC phenotype. [ABSTRACT FROM AUTHOR]- Published
- 2015
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13. Genomic profiling of inflammatory breast cancer: A review.
- Author
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Bertucci, François, Finetti, Pascal, Vermeulen, Peter, Van Dam, Peter, Dirix, Luc, Birnbaum, Daniel, Viens, Patrice, and Van Laere, Steven
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INFLAMMATORY breast cancer ,GENETICS of breast cancer ,MEDICAL literature reviews ,DNA microarrays ,RARE diseases ,CANCER chemotherapy ,BREAST cancer treatment - Abstract
Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer. Despite efforts in the past decade to delineate the molecular biology of IBC by applying high-throughput molecular profiling technologies to clinical samples, IBC remains insufficiently characterized. The reasons for that include limited sizes of the study population, heterogeneity with respect to the composition of the IBC and non-IBC control groups and technological differences across studies. In 2008, the World IBC Consortium was founded to foster collaboration between research groups focusing on IBC. One of the initial projects was to redefine the molecular profile of IBC using an unprecedented number of samples and search for gene signatures associated with survival and response to neo-adjuvant chemotherapy. Here, we provide an overview of all the molecular profiling studies that have been performed on IBC clinical samples to date. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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14. High-Resolution Comparative Genomic Hybridization of Inflammatory Breast Cancer and Identification of Candidate Genes.
- Author
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Bekhouche, Ismahane, Finetti, Pascal, Adelaïde, José, Ferrari, Anthony, Tarpin, Carole, Charafe-Jauffret, Emmanuelle, Charpin, Colette, Houvenaeghel, Gilles, Jacquemier, Jocelyne, Bidaut, Ghislain, Birnbaum, Daniel, Viens, Patrice, Chaffanet, Max, and Bertucci, François
- Subjects
- *
INFLAMMATORY breast cancer , *INFLAMMATION , *MESSENGER RNA , *CANCER genes , *GENOTYPE-environment interaction - Abstract
Background: Inflammatory breast cancer (IBC) is an aggressive form of BC poorly defined at the molecular level. We compared the molecular portraits of 63 IBC and 134 non-IBC (nIBC) clinical samples. Methodology/Findings: Genomic imbalances of 49 IBCs and 124 nIBCs were determined using high-resolution array-comparative genomic hybridization, and mRNA expression profiles of 197 samples using whole-genome microarrays. Genomic profiles of IBCs were as heterogeneous as those of nIBCs, and globally relatively close. However, IBCs showed more frequent "complex" patterns and a higher percentage of genes with CNAs per sample. The number of altered regions was similar in both types, although some regions were altered more frequently and/or with higher amplitude in IBCs. Many genes were similarly altered in both types; however, more genes displayed recurrent amplifications in IBCs. The percentage of genes whose mRNA expression correlated with CNAs was similar in both types for the gained genes, but ∼7-fold lower in IBCs for the lost genes. Integrated analysis identified 24 potential candidate IBC-specific genes. Their combined expression accurately distinguished IBCs and nIBCS in an independent validation set, and retained an independent prognostic value in a series of 1,781 nIBCs, reinforcing the hypothesis for a link with IBC aggressiveness. Consistent with the hyperproliferative and invasive phenotype of IBC these genes are notably involved in protein translation, cell cycle, RNA processing and transcription, metabolism, and cell migration. Conclusions: Our results suggest a higher genomic instability of IBC. We established the first repertory of DNA copy number alterations in this tumor, and provided a list of genes that may contribute to its aggressiveness and represent novel therapeutic targets. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
15. Gene Expression Profiling of Inflammatory Breast Cancer.
- Author
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Bertucci, François, Finetti, Pascal, Birnbaum, Daniel, and Viens, Patrice
- Subjects
- *
INFLAMMATORY breast cancer , *GENE expression , *DNA microarrays , *CLUSTER analysis (Statistics) , *CANCER education , *RNA - Abstract
The article presents a study on the conduction of gene expression profiling studies on inflammatory breast cancer (IBC) clinical samples. The study focused on IBC and non-IBC profile samples and results showed the feasibility of messenger RNA expression from IBC biopsies and great transcriptional heterogeneity of IBC and the existence of molecular subtypes similar to non-IBC. It is concluded that there is a need for larger series of IBC samples using homogenous criteria.
- Published
- 2010
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16. The PD1/PDL1 axis, a promising therapeutic target in aggressive breast cancers.
- Author
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Bertucci, François, Finetti, Pascal, Birnbaum, Daniel, and Mamessier, Emilie
- Subjects
- *
BREAST cancer treatment , *MESSENGER RNA , *IMMUNE response , *CANCER chemotherapy , *LYMPHOCYTES - Abstract
Analysis ofPDL1mRNA expression in ∼5,500 breast cancers showedPDL1upregulation in 38% of basal tumors and 38% of inflammatory breast cancers (IBC). Upregulation, associated with signs of strong cytotoxic local immune response, was associated with a better survival in the basal or triple-negative subtypes, and with a better pathological response to chemotherapy in these subtypes and IBC. Reactivation of dormant tumor-infiltrating lymphocytes (TILs) by PD1/PDL1-inhibitors represents a promising strategy in these aggressive tumors. [ABSTRACT FROM PUBLISHER]
- Published
- 2016
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17. Characterization and Targeting of Platelet-Derived Growth Factor Receptor alpha (PDGFRA) in Inflammatory Breast Cancer (IBC).
- Author
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Joglekar-Javadekar, Madhura, Van Laere, Steven, Bourne, Michael, Moalwi, Manal, Finetti, Pascal, Vermeulen, Peter B., Birnbaum, Daniel, Dirix, Luc Y., Ueno, Naoto, Carter, Monique, Rains, Justin, Ramachandran, Abhijit, Bertucci, Francois, and van Golen, Kenneth L.
- Subjects
- *
PLATELET-derived growth factor receptors , *INFLAMMATORY breast cancer , *CANCER invasiveness , *GENE targeting , *GENE expression , *PROGRESSION-free survival , *CANCER treatment - Abstract
PURPOSE: Inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer due to its rapid onset and highly invasive nature. IBC carries 5- and 10-year disease-free survival rates of ~45% and b20%, respectively. Multiple studies demonstrate that in comparison with conventional breast cancer, IBC has a unique molecular identity. Here, we have identified platelet-derived growth factor receptor alpha (PDGFRA) as being uniquely expressed and active in IBC patient tumor cells. EXPERIMENTAL DESIGN: Here we focus on characterizing and targeting PDGFRA in IBC. Using gene expression, we analyzed IBC patient samples and compared them with non- IBC patient samples. Further, using IBC cells in culture, we determined the effect of small molecules inhibitors in both in vitro and in vivo assays. RESULTS: In IBC patients, we show more frequent PDGFRA activation signature than non-IBC samples. In addition, the PDGFRA activation signature is associated with shorter metastasis-free survival in both uni- and multivariate analyses. We also demonstrate that IBC cells express active PDGFRA. Finally, we show that PDGFRA targeting by crenolanib (CP-868-596), but not imatinib (STI571), two small molecule inhibitors, interferes with IBC cell growth and emboli formation in vitro and tumor growth in vivo. CONCLUSIONS: Our data suggest that PDGFRA may be a promising target for therapy in IBC. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
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