المؤلفون: Andre, F., Filleron, T., Kamal, M., Mosele, F., Arnedos, M., Dalenc, Florence, Sablin, M. P., Campone, M., Bonnefoi, H., Lefeuvre-Plesse, Claudia, Jacot, William, Coussy, F., Ferrero, J. M., Emile, G., Mouret-Reynier, Marie Ange, Thery, J. C., Isambert, Nicolas, Mege, A., Barthelemy, Philippe, You, B., Hajjaji, Nawale, Lacroix, L., Rouleau, E., Tran-Dien, A., Boyault, S., Attignon, V., Gestraud, Pierre, Servant, N., Le Tourneau, C., Cherif, L. L., Soubeyran, I., Montemurro, F., Morel, A., Lusque, A., Jimenez, M., Jacquet, A., Gonçalves, A., Bachelot, T., Bieche, I.

المساهمون: Université de Lille, Inserm, CHU Lille, Institut Gustave Roussy IGR, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse U981, Institut Claudius Regaud, Institut Curie - Saint Cloud ICSC, Institut de Cancérologie de l'Ouest Angers/Nantes UNICANCER/ICO, Institut Bergonié Bordeaux, CRLCC Eugène Marquis CRLCC, Institut de Recherche en Cancérologie de Montpellier IRCM - U1194 Inserm - UM, Centre de Lutte contre le Cancer Antoine Lacassagne Nice UNICANCER/CAL, Centre Jean Perrin Clermont-Ferrand UNICANCER/CJP, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen CLCC Henri Becquerel, Département d'oncologie médicale Centre Georges-François Leclerc, Centre Régional de Lutte contre le cancer Georges-François Leclerc Dijon UNICANCER/CRLCC-CGFL, Institut Sainte Catherine Avignon, Institut de Cancérologie de Strasbourg Europe ICANS, Université Claude Bernard Lyon 1 UCBL, Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U1192, Centre Léon Bérard Lyon, Mines Paris - PSL (École nationale supérieure des mines de Paris), CRLCC - Centre Paul Papin CRLCC Paul Papin, Institut Cochin IC UM3 (UMR 8104 / U1016), Institut Curie Paris

الوصف: Cancer progression is driven in part by genomic alterations1. The genomic characterization of cancers has shown interpatient heterogeneity regarding driver alterations2, leading to the concept that generation of genomic profiling in patients with cancer could allow the selection of effective therapies3,4. Although DNA sequencing has been implemented in practice, it remains unclear how to use its results. A total of 1,462 patients with HER2-non-overexpressing metastatic breast cancer were enroled to receive genomic profiling in the SAFIR02-BREAST trial. Two hundred and thirty-eight of these patients were randomized in two trials (nos. NCT02299999 and NCT03386162) comparing the efficacy of maintenance treatment5 with a targeted therapy matched to genomic alteration. Targeted therapies matched to genomics improves progression-free survival when genomic alterations are classified as level I/II according to the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT)6 (adjusted hazards ratio (HR): 0.41, 90% confidence interval (CI): 0.27–0.61, P < 0.001), but not when alterations are unselected using ESCAT (adjusted HR: 0.77, 95% CI: 0.56–1.06, P = 0.109). No improvement in progression-free survival was observed in the targeted therapies arm (unadjusted HR: 1.15, 95% CI: 0.76–1.75) for patients presenting with ESCAT alteration beyond level I/II. Patients with germline BRCA1/2 mutations (n = 49) derived high benefit from olaparib (gBRCA1: HR = 0.36, 90% CI: 0.14–0.89; gBRCA2: HR = 0.37, 90% CI: 0.17–0.78). This trial provides evidence that the treatment decision led by genomics should be driven by a framework of target actionability in patients with metastatic breast cancer.

وصف الملف: application/pdf

العلاقة: Nature; http://hdl.handle.net/20.500.12210/92593Test

الإتاحة: https://doi.org/20.500.12210/92593Test
https://hdl.handle.net/20.500.12210/92593Test

المؤلفون: Bieche I., Coussy F., El-Botty R., Vacher S., Chateau-Joubert S., Dahmani A., Montaudon E., Reyes C., Gentien D., Reyal F., Ricci F., Nicolas A., Marchio' C., Vincent-Salomon A., Lae M., Marangoni E.

المساهمون: Bieche I., Coussy F., El-Botty R., Vacher S., Chateau-Joubert S., Dahmani A., Montaudon E., Reyes C., Gentien D., Reyal F., Ricci F., Nicolas A., Marchio' C., Vincent-Salomon A., Lae M., Marangoni E.

مصطلحات موضوعية: Adenomyoepithelioma, HRAS, MEK inhibitor, PDX

الوصف: Malignant adenomyoepithelioma (AME) of the breast is an exceptionally rare form of breast cancer, with a significant metastatic potential. Chemotherapy has been used in the management of advanced AME patients, however the majority of treatments are not effective. Recent studies report recurrent mutations in the HRAS Q61 hotspot in small series of AMEs, but there are no preclinical or clinical data showing H-Ras protein as a potential therapeutic target in malignant AMEs. We performed targeted sequencing of tumours' samples from new series of 13 AMEs, including 9 benign and 4 malignant forms. Samples from the breast tumour and the matched axillary metastasis of one malignant HRAS mutated AME were engrafted and two patient-derived xenografts (PDX) were established that reproduced the typical AME morphology. The metastasis- derived PDX was treated in vivo by different chemotherapies and a combination of MEK and BRAF inhibitors (trametinib and dabrafenib). All malignant AMEs presented a recurrent mutation in the HRAS G13R or G12S hotspot. Mutation of PIK3CA were found in both benign and malignant AMEs, while AKT1 mutations were restricted to benign AMEs. Treatment of the PDX by the MEK inhibitor trametinib, resulted in a marked anti-tumor activity, in contrast to the BRAF inhibitor and the different chemotherapies that were ineffective. Overall, these findings further expand on the genetic features of AMEs and suggest that patients carrying advanced HRAS-mutated AMEs could potentially be treated with MEK inhibitors.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34496925; info:eu-repo/semantics/altIdentifier/wos/WOS:000693808900003; volume:14; issue:1; firstpage:143; lastpage:147; numberofpages:5; journal:JOURNAL OF HEMATOLOGY & ONCOLOGY; http://hdl.handle.net/2318/1801919Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85114491798; https://pubmed.ncbi.nlm.nih.gov/34496925Test/

الإتاحة: https://doi.org/10.1186/s13045-021-01158-3Test
http://hdl.handle.net/2318/1801919Test
https://pubmed.ncbi.nlm.nih.gov/34496925Test/

المؤلفون: Agostinetto, E., Paesmans, M., Ameye, L., Veys, I., Buisseret, L., Neven, P., Taylor, D., Fontaine, C., Duhoux, F.P., Canon, J-L., Denys, H., Coussy, F., Chakiba, C., Pistilli, B., Piccart, M., Ignatiadis, M., Aftimos, P.G.

المصدر: Annals of Oncology ; volume 32, page S52 ; ISSN 0923-7534

مصطلحات موضوعية: Oncology, Hematology

الإتاحة: https://doi.org/10.1016/j.annonc.2021.03.086Test
https://api.elsevier.com/content/article/PII:S0923753421009649?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0923753421009649?httpAccept=text/plainTest

المؤلفون: Coussy, F., El Botty, R., Lavigne, M., Gu, C., Fuhrmann, L., Briaux, A., de Koning, L., Dahmani, A., Montaudon, E., Morisset, L., Huguet, L., Sourd, L., Painsec, P., Chateau-Joubert, S., Larcher, Thibaut, Vacher, S., Melaabi, S., Salomon, A. Vincent, Marangoni, E., Bieche, I.

المساهمون: Unit of Pharmacogenomics, Department of Genetics,Laboratory of Preclinical Investigation, Department of Translational Research,Department of Medical Oncology, Institut Curie Paris, Laboratory of Preclinical Investigation, Department of Translational Research, Institut Curie Research Center, Department of Biopathology, Università degli Studi di Roma Tor Vergata Roma = University of Rome Tor Vergata, Unit of Pharmacogenomics, Department of Genetics, Translational Research Department, RPPA Platform, Biopôle Alfort, École nationale vétérinaire d'Alfort (ENVA), Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Expertise en Anatomie Pathologique (APEX), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Descartes - Paris 5 (UPD5)

المصدر: ISSN: 1756-8722 ; Journal of Hematology and Oncology ; https://hal.science/hal-02508763Test ; Journal of Hematology and Oncology, 2020, 13 (1), ⟨10.1186/s13045-020-0846-y⟩.

مصطلحات موضوعية: [SDV]Life Sciences [q-bio]

الوصف: Combination of PI3K and MEK inhibitors yields durable remission in PDX models of PIK3CA-mutated metaplastic breast cancers

العلاقة: hal-02508763; https://hal.science/hal-02508763Test; https://hal.science/hal-02508763/documentTest; https://hal.science/hal-02508763/fileTest/Coussy%202020%20METAPLASTIC%20BC_1.pdf; PRODINRA: 496776; WOS: 00517313400001

الإتاحة: https://doi.org/10.1186/s13045-020-0846-yTest
https://hal.science/hal-02508763Test
https://hal.science/hal-02508763/documentTest
https://hal.science/hal-02508763/fileTest/Coussy%202020%20METAPLASTIC%20BC_1.pdf

المؤلفون: Coussy, F, Lallemand, F, Vacher, S, Schnitzler, A, Chemlali, W, Caly, M, Nicolas, A, Richon, S, Meseure, D, El Botty, R, De-Plater, L, Fuhrmann, L, Dubois, T, Roman-Roman, S, Dangles-Marie, V, Marangoni, E, Bièche, I

المصدر: British Journal of Cancer ; volume 116, issue 12, page 1595-1603 ; ISSN 0007-0920 1532-1827

مصطلحات موضوعية: Cancer Research, Oncology

الإتاحة: https://doi.org/10.1038/bjc.2017.131Test
http://www.nature.com/articles/bjc2017131.pdfTest
http://www.nature.com/articles/bjc2017131Test

المؤلفون: Agostinetto, E, Nader-Marta, G, Paesmans, M, Ameye, L, Veys, I, Buisseret, L, Neven, P, Taylor, D, Fontaine, C, Duhoux, FP, Canon, JL, Denys, Hannelore, Coussy, F, Chakiba, C, Ribeiro, JM, Piccart, M, Desmedt, C, Ignatiadis, M, Aftimos, P

المصدر: FUTURE ONCOLOGY ; ISSN: 1479-6694 ; ISSN: 1744-8301

مصطلحات موضوعية: Medicine and Health Sciences, ROS1, neoadjuvant, lobular, entrectinib, breast cancer

الوصف: Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC. Plain language summary: Breast cancer is the most common cancer among women worldwide. Breast cancer is not a unique disease, but rather a heterogeneous disease, with different subtypes. Lobular breast cancer is the second most common histologic subtype of breast cancer after ductal breast cancer. Lobular breast cancer has some peculiar characteristics that make it a distinct entity in the context of breast cancer. Nevertheless, few clinical studies so far have focused specifically on this subtype. ROSALINE is a clinical study aimed to test entrectinib, a new drug that showed promising activity in preliminary research studies, in combination with endocrine therapy in women with lobular breast cancer before surgery.

وصف الملف: application/pdf

العلاقة: https://biblio.ugent.be/publication/01GYFN90HPWM2QB65C77CEV6YCTest; http://hdl.handle.net/1854/LU-01GYFN90HPWM2QB65C77CEV6YCTest; http://doi.org/10.2217/fon-2022-0358Test; https://biblio.ugent.be/publication/01GYFN90HPWM2QB65C77CEV6YC/file/01HVP3KG2XTBEEXDW2SM489JR8Test

الإتاحة: https://doi.org/10.2217/fon-2022-0358Test
https://biblio.ugent.be/publication/01GYFN90HPWM2QB65C77CEV6YCTest
http://hdl.handle.net/1854/LU-01GYFN90HPWM2QB65C77CEV6YCTest
https://biblio.ugent.be/publication/01GYFN90HPWM2QB65C77CEV6YC/file/01HVP3KG2XTBEEXDW2SM489JR8Test

المؤلفون: Bonnefoi, H., Grellety, T., Tredan, O., Saghatchian, M., Dalenc, F., Mailliez, A., L'Haridon, T., Cottu, P., Abadie-Lacourtoisie, S., You, B., Mousseau, M., Dauba, J., Del Piano, F., Desmoulins, I., Coussy, F., Madranges, N., Grenier, J., Bidard, F.C., Proudhon, C., MacGrogan, G., Orsini, C., Pulido, M., Gonçalves, A.

المصدر: Annals of Oncology ; volume 27, issue 5, page 812-818 ; ISSN 0923-7534

مصطلحات موضوعية: Oncology, Hematology

الإتاحة: https://doi.org/10.1093/annonc/mdw067Test
https://api.elsevier.com/content/article/PII:S0923753419374435?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0923753419374435?httpAccept=text/plainTest

المؤلفون: Ferron, G., De Rauglaudre, G., Ray-Coquard, I.L., Lesoin, A., Joly, F., Lortholary, A., Raban, N., Peron, J., Malaurie-Agostini, E., Gouy, S., Kaminsky, M.-C., Meunier, J., Alexandre, J., Berton-Rigaud, D., Coussy, F., Favier, L., Venat-Bouvet, L., Marmion, F., Combe, P., Pujade-Lauraine, E.

المصدر: Annals of Oncology ; volume 27, page vi297 ; ISSN 0923-7534

مصطلحات موضوعية: Oncology, Hematology

الإتاحة: https://doi.org/10.1093/annonc/mdw374.06Test
https://api.elsevier.com/content/article/PII:S0923753419444864?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0923753419444864?httpAccept=text/plainTest
http://academic.oup.com/annonc/article-pdf/27/suppl_6/859PD/19450723/mdw374.06.pdfTest

المؤلفون: Giacchetti, S., Porcher, R., Lehmann-Che, J., Hamy, A. S., Roquancourt, A., De, Cuvier, C., Cottu, P. H., Bertheau, P., Albiter, M., Bouhidel, F., Coussy, F., Extra, J. M., Marty, M., de Thé, Hugues, Espie, M.

المساهمون: Collège de France - Chaire Oncologie cellulaire et moléculaire, Génomes, biologie cellulaire et thérapeutiques (GenCellDis (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

المصدر: ISSN: 0007-0920.

مصطلحات موضوعية: [SDV.CAN]Life Sciences [q-bio]/Cancer

الوصف: International audience ; BACKGROUND: Triple-negative (TN) breast cancers exhibit major initial responses to neoadjuvant chemotherapy, but generally have a poor outcome. Because of the lack of validated drug targets, chemotherapy remains an important therapeutic tool in these cancers. METHODS: We report the survival of two consecutive series of 267 locally advanced breast cancers (LABC) treated with two different neoadjuvant regimens, either a dose-dense and dose-intense cyclophosphamide-anthracycline (AC) association (historically called SIM) or a conventional sequential association of cyclophosphamide and anthracycline, followed by taxanes (EC-T). We compared pathological responses and survival rates of these two groups and studied their association with tumours features. RESULTS: Although the two regimens showed equivalent pathological complete response (pCR) in the whole population (16 and 12%), the SIM regimen yielded a non-statistically higher pCR rate than EC-T (48% vs 24%, P=0.087) in TN tumours. In the SIM protocol, DFS was statistically higher for TN than for non-TN patients (P=0.019), although we showed that the TN status was associated with an increased initial risk of recurrence in both regimens. This effect gradually decreased and after 2 years, TN was associated with a significantly decreased likelihood of relapse in SIM-treated LABC (hazard ratio (HR)=0.25 (95% CI: 0.07-0.86), P=0.028). CONCLUSIONS: AC dose intensification treatment is associated with a very favourable long-term survival rate in TN breast cancers. These observations call for a prospective assessment of such dose-intense AC-based regimens in locally advanced TN tumours.

العلاقة: hal-03653840; https://hal.science/hal-03653840Test; https://hal.science/hal-03653840/documentTest; https://hal.science/hal-03653840/file/bjc201481.pdfTest; PUBMEDCENTRAL: PMC3960631

الإتاحة: https://doi.org/10.1038/bjc.2014.81Test
https://hal.science/hal-03653840Test
https://hal.science/hal-03653840/documentTest
https://hal.science/hal-03653840/file/bjc201481.pdfTest

المؤلفون: Coussy, F., El-Botty, R., Château-Joubert, S., Dahmani, A., Montaudon, E., Leboucher, S., Morisset, L., Painsec, P., Sourd, L., Huguet, L., Nemati, F., Servely, J.-L., Larcher, T., Vacher, S., Briaux, A., Reyes, C., La Rosa, P., Lucotte, G., Popova, T., Foidart, Pierre, Sounni, Nor Eddine, Noël, Agnès, Decaudin, D., Fuhrmann, L., Salomon, A., Reyal, F., Mueller, C., Brugge, P. T., Jonkers, J., Poupon, M.-F., Stern, M.-H., Bièche, I., Pommier, Y., Marangoni, E.

المصدر: Science Translational Medicine, 12 (532) (2020)

مصطلحات موضوعية: DNA topoisomerase inhibitor, Article, BRCAness gene, RB1 gene, SLFN11 gene, Human health sciences, Oncology, Sciences de la santé humaine, Oncologie

الوصف: peer reviewed ; Topoisomerase I (TOP1) inhibitors trap TOP1 cleavage complexes resulting in DNA double-strand breaks (DSBs) during replication, which are repaired by homologous recombination (HR). Triple-negative breast cancer (TNBC) could be eligible for TOP1 inhibitors given the considerable proportion of tumors with a defect in HR-mediated repair (BRCAness). The TOP1 inhibitor irinotecan was tested in 40 patient-derived xenografts (PDXs) of TNBC. BRCAness was determined with a single-nucleotide polymorphism (SNP) assay, and expression of Schlafen family member 11 (SLFN11) and retinoblastoma transcriptional corepressor 1 (RB1) was evaluated by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry analyses. In addition, the combination of irinotecan and the ataxia telangiectasia and Rad3-related protein (ATR) inhibitor VE-822 was tested in SLFN11-negative PDXs, and two clinical non-camptothecin TOP1 inhibitors (LMP400 and LMP776) were tested. Thirty-eight percent of the TNBC models responded to irinotecan. BRCAness combined with high SLFN11 expression and RB1 loss identified highly sensitive tumors, consistent with the notion that deficiencies in cell cycle checkpoints and DNA repair result in high sensitivity to TOP1 inhibitors. Treatment by the ATR inhibitor VE-822 increased sensitivity to irinotecan in SLFN11-negative PDXs and abolished irinotecan-induced phosphorylation of checkpoint kinase 1 (CHK1). LMP400 (indotecan) and LMP776 (indimitecan) showed high antitumor activity in BRCA1-mutated or BRCAness-positive PDXs. Last, low SLFN11 expression was associated with poor survival in 250 patients with TNBC treated with anthracycline-based chemotherapy. In conclusion, a substantial proportion of TNBC respond to irinotecan. BRCAness, high SLFN11 expression, and RB1 loss are highly predictive of response to irinotecan and the clinical indenoisoquinoline TOP1 inhibitors. Copyright © 2020 The Authors, some rights reserved.

العلاقة: urn:issn:1946-6234; urn:issn:1946-6242; https://orbi.uliege.be/handle/2268/249408Test; info:hdl:2268/249408; scopus-id:2-s2.0-85079795061; info:pmid:32075943

الإتاحة: https://doi.org/10.1126/scitranslmed.aax2625Test
https://orbi.uliege.be/handle/2268/249408Test