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151. Abstract P5-12-09: The ≥5% cut-off reveals tumor PD-L1 positivity as potential selection biomarker for patient enrollment into the trials evaluating anti-PD-1 or anti-PD-L1 agents in neoadjuvant treatment of triple negative breast cancer

Author

Finck, W, primary, Passildas, J, additional, Poirier, C, additional, Kwiatkowski, F, additional, Abrial, C, additional, Durando, X, additional, Penault-Llorca, F, additional, and Radosevic-Robin, N, additional

Published
2019
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152. Abstract P3-11-10: Prosigna prognostic signature in pN1mi, estrogen receptor-positive breast cancer:the pN categorization impacts the BC risk stratification

Author

Charafe-Jauffret, E, primary, Duprez-Paumier, R, additional, Berghian, A, additional, Penault-Llorca, F, additional, Dauplat, MM, additional, Boucraut, A, additional, Cohen, M, additional, Houvenaeghel, G, additional, Maroc, C, additional, Pradines, A, additional, Cayre, A, additional, Etancelin, P, additional, and Lacroix-triki, M, additional

Published
2019
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155. CHECK'UP: A prospective cohort study to identify predictive factors of response and mechanisms of resistance to PD-1 and PD-L1 antagonists

Author

Penault-Llorca, F., primary, Caux, C., additional, Depil, S., additional, Le Tourneau, C., additional, Pérol, M., additional, Robert, C., additional, Soumelis, V., additional, Couch, D., additional, Isambert, N., additional, Fernandez, Y., additional, Filleron, T., additional, and Vassal, G., additional

Published
2018
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156. MA26.06 Crizotinib-Treated ALK Immunopositive Metastasized NSCLC is Associated with an Unfavorable Prognosis when FISH Negative

Author

Thunnissen, E., primary, Lissenberg-Witte, B., additional, Van Den Heuvel, M., additional, Monkhorst, K., additional, Skov, B., additional, Sorensen, J., additional, Mellemgaard, A., additional, Dingemans, A., additional, Speel, E., additional, De Langen, J., additional, Hashemi, S., additional, Bahce, I., additional, Van Der Drift, M., additional, Büttner, R., additional, Looijen Salomon, M., additional, Gosney, J., additional, Postmus, P.E., additional, Samii, S., additional, Duplaquet, F., additional, Weynand, B., additional, Durando, X., additional, Penault-Llorca, F., additional, Finn, S., additional, Oz, B., additional, Akyurek, N., additional, Wolf, J., additional, Bubendorf, L., additional, Hiemstra, A., additional, Duin, S., additional, Marondel, I., additional, Timens, W., additional, Schuuring, E., additional, Pauwels, P., additional, and Smit, E., additional

Published
2018
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157. Gene expression (GE)-based biomarkers associated with nivolumab response in a real-life cohort of patients with metastatic non-small cell lung cancer (mNSCLC)

Author

Radosevic-Robin, N., primary, Ong, S., additional, Warren, S.E., additional, Kossai, M., additional, Godfraind, C., additional, Masson, M., additional, Janicot, H., additional, Merle, P., additional, Dubray-Longueras, P., additional, Durando, X., additional, Morel, P., additional, Cesano, A., additional, and Penault-Llorca, F., additional

Published
2018
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158. MA26.07 ROS1 (SP384) Immunohistochemistry Inter-Reader Precision Between 12 Pathologists

Author

Hanlon Newell, A., primary, Liu, W., additional, Bubendorf, L., additional, Büttner, R., additional, Kerr, K., additional, Kockx, M., additional, Kossai, M., additional, Lopez-Rios, F., additional, Marchetti, A., additional, Marondel, I., additional, Nicholson, A., additional, Oz, B., additional, Pauwels, P., additional, Penault-Llorca, F., additional, Rossi, G., additional, Rüsseler, V., additional, Thunnissen, E., additional, Pate, G., additional, Portier, B., additional, Faure, C., additional, Le, C., additional, Smith, D., additional, Menzl, I., additional, and Huang, R., additional

Published
2018
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159. Shared decision of adjuvant chemotherapy including a genomic test: 1 year patients reported outcomes in a multicenter, national clinical trial (UCBG-2-14)

Author

Lefèvre, S., primary, Kwiatkowski, F., additional, Lemonnier, J., additional, Levy, C., additional, Leheurteur, M., additional, Uwer, L., additional, Derbel, O., additional, Le Rol, A., additional, Jacquin, J.P., additional, Jouannaud, C., additional, Quenel-Tueux, N., additional, Girre, V., additional, Boinon, D., additional, Penault-Llorca, F., additional, and Delaloge, S., additional

Published
2018
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161. Abstract P5-22-18: Withdrawn

Author

Cohen, M, primary, Benhaim, S, additional, Chauvet, M-P, additional, Penault-Llorca, F, additional, Bertrand, P, additional, Giraud, S, additional, Opinel, P, additional, Faure, C, additional, Meynard, P, additional, Charafe, E, additional, and Houvenaeghel, G, additional

Published
2018
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163. Abstract P1-09-11: A phase Ib study of oral administration of lucitanib in combination with fulvestrant in patients with HR+ metastatic breast cancer (mBC)

Author

Campone, M, primary, Bachelot, T, additional, Penault-Llorca, F, additional, Pallis, A, additional, Agrapart, V, additional, Pierrat, M-J, additional, Poirot, C, additional, Paux, G, additional, Dubois, F, additional, Xuereb, L, additional, Robert, R, additional, and Andre, F, additional

Published
2018
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165. ROS1 (SP384) Immunohistochemistry Inter-Reader Precision Between 12 Pathologists

Author

Newell, A. Hanlon, Liu, W., Bubendorf, L., Buettner, R., Kerr, K., Kockx, M., Kossai, M., Lopez-Rios, F., Marchetti, A., Marondel, I., Nicholson, A., Oz, B., Pauwels, P., Penault-Llorca, F., Rossi, G., Russeler, V., Thunnissen, E., Pate, G., Portier, B., Faure, C., Le, C., Smith, D., Menzl, I., Huang, R., Newell, A. Hanlon, Liu, W., Bubendorf, L., Buettner, R., Kerr, K., Kockx, M., Kossai, M., Lopez-Rios, F., Marchetti, A., Marondel, I., Nicholson, A., Oz, B., Pauwels, P., Penault-Llorca, F., Rossi, G., Russeler, V., Thunnissen, E., Pate, G., Portier, B., Faure, C., Le, C., Smith, D., Menzl, I., and Huang, R.

Published
2018

166. Crizotinib-Treated ALK Immunopositive Metastasized NSCLC is Associated with an Unfavorable Prognosis when FISH Negative

Author

Thunnissen, E., Lissenberg-Witte, B., Van den Heuvel, M., Monkhorst, K., Skov, B., Sorensen, J., Mellemgaard, A., Dingemans, A., Speel, E., De langen, J., Hashemi, S., Bahce, I., Van Der Drift, M., Buettner, R., Salomon, M. Looijen, Gosney, J., Postmus, P. E., Samii, S., Duplaquet, F., Weynand, B., Durando, X., Penault-Llorca, F., Finn, S., Oz, B., Akyurek, N., Wolf, J., Bubendorf, L., Hiemstra, A., Duin, S., Marondel, L., Timens, W., Schuuring, E., Pauwels, P., Smit, E., Thunnissen, E., Lissenberg-Witte, B., Van den Heuvel, M., Monkhorst, K., Skov, B., Sorensen, J., Mellemgaard, A., Dingemans, A., Speel, E., De langen, J., Hashemi, S., Bahce, I., Van Der Drift, M., Buettner, R., Salomon, M. Looijen, Gosney, J., Postmus, P. E., Samii, S., Duplaquet, F., Weynand, B., Durando, X., Penault-Llorca, F., Finn, S., Oz, B., Akyurek, N., Wolf, J., Bubendorf, L., Hiemstra, A., Duin, S., Marondel, L., Timens, W., Schuuring, E., Pauwels, P., and Smit, E.

Published
2018

167. Personalized cancer medicine and the future of pathology

Author

Moch, H., Blank, P., Dietel, M., Elmberger, G., Kerr, K., Palacios, J., Penault-Llorca, F., Rossi, G., Szucs, T., Moch, H., Blank, P., Dietel, M., Elmberger, G., Kerr, K., Palacios, J., Penault-Llorca, F., Rossi, G., and Szucs, T.

Abstract

In February 2011, a group of pathologists from different departments in Europe met in Zurich, Switzerland, to discuss opportunities and challenges for pathology in the era of personalized medicine. The major topics of the meeting were assessment of the role of pathology in personalized medicine, its future profile among other biomedical disciplines with an interest in personalized medicine as well as the evolution of companion diagnostics. The relevance of novel technologies for genome analysis in clinical practice was discussed. The participants recognize that there should be more initiatives taken by the pathology community in companion diagnostics and in the emerging field of next-generation sequencing and whole genome analysis. The common view of the participants was that the pathology community has to be mobilized for stronger engagement in the future of personalized medicine. Pathologists should be aware of the challenges and the analytical opportunities of the new technologies. Challenges of clinical trial design as well as insurance and reimbursement questions were addressed. The pathology community has the responsibility to lead medical colleagues into embracing this new area of genomic medicine. Without this effort, the discipline of pathology risks losing its key position in molecular tissue diagnostics

Published
2018

168. Corrigendum to '3rd ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 3)' [Breast 31 (February 2017) 244-259]

Author

Cardoso, F., Costa, A., Senkus, E., Aapro, M., Andre, F., Barrios, C.H., Bergh, J., Bhattacharyya, G., Biganzoli, L., Cardoso, M.J., Carey, L., Corneliussen-James, D, Curigliano, G, Dieras, V, El Saghir, N, Eniu, E, Fallowfield, L., Fenech, E, Francis, D, Gelmon, B, Gennari, D, Hudis, B, Kaufman, B., Krop, B, Meijer, D, Mertz, B, Ohno, B, Pagani, B, Papadopoulos, E., Peccatori, E, Penault-Llorca, L, Piccart, L, Pierga, D, Rugo, B, Shockney, L., Sledge, A, Swain, L, Thomssen, E, Tutt, L, Vorobiof, D., Xu, B., Norton, L., Winer, E., Eniu, A., Fenech, D., Francis, P., Gelmon, K., Gennari, A., Harbeck, N., Hudis, C., Krop, I., Mayer, M., Meijer, H., Mertz, S., Ohno, S., Pagani, O., Peccatori, F., Penault-Llorca, F., Piccart, M.J., Pierga, J.Y., Rugo, H., Sledge, G., Swain, S., Thomssen, C., Tutt, A., European School of Oncology & Breast Unit, Champalimaud Clinical Center, Lisbon, Portugal, Champalimaud Clinical Center, European Institute of Oncology [Milan] (ESMO), Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland, Medical University of Gdansk, Breast Center, Genolier Cancer Center, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR), Department of Medicine, PUCRS School of Medicine, Department of Oncology–Pathology, Radiumhemmet, Karolinska University Hospital [Stockholm], Department of Medical Oncology, Fortis Hospital, 'Sandro Pitigliani' Medical Oncology Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Breast Unit, Department of Hematology and Oncology, Lineberger Comprehensive Cancer Center (UNC Lineberger), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC)-University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), METAvivor Research and Support, MetaVivor Research and Support, Division of Experimental Therapeutics, Department of Medical Oncology, Institut Curie, Paris 75248, France, Brustzentrum der Universitat München, Universität München, Advanced BC.org, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, business.industry, Advanced breast, Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, medicine.disease, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Surgery, business, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2017
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171. Do Spanish Medical Students Understand the Concept of Brain Death?

Author

Ríos, Antonio, primary, López-Navas, A., additional, López-López, A., additional, Gómez, F. J., additional, Iriarte, J., additional, Herruzo, R., additional, Blanco, G., additional, Llorca, F. J., additional, Asunsolo, A., additional, Sánchez, P., additional, Gutiérrez, P. R., additional, Fernández, A., additional, de Jesús, M. T., additional, Alarcón, L. Martínez, additional, del Olivo, M., additional, Fuentes, L., additional, Hernández, J. R., additional, Virseda, J., additional, Yelamos, J., additional, Bondía, J. A., additional, Hernández, A. M., additional, Ayala, M. A., additional, Ramírez, P., additional, and Parrilla, P., additional

Published
2018
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172. Correction to: 3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3)

Author

Cardoso, F., primary, Costa, A., additional, Senkus, E., additional, Aapro, M., additional, André, F., additional, Barrios, C.H., additional, Bergh, J., additional, Bhattacharyya, G., additional, Biganzoli, L., additional, Cardoso, M.J., additional, Carey, L., additional, Corneliussen-James, D., additional, Curigliano, G., additional, Dieras, V., additional, El Saghir, N., additional, Eniu, A., additional, Fallowfield, L., additional, Fenech, D., additional, Francis, P., additional, Gelmon, K., additional, Gennari, A., additional, Harbeck, N., additional, Hudis, C., additional, Kaufman, B., additional, Krop, I., additional, Mayer, M., additional, Meijer, H., additional, Mertz, S., additional, Ohno, S., additional, Pagani, O., additional, Papadopoulos, E., additional, Peccatori, F., additional, Penault-Llorca, F., additional, Piccart, M.J., additional, Pierga, J.Y., additional, Rugo, H., additional, Shockney, L., additional, Sledge, G., additional, Swain, S., additional, Thomssen, C., additional, Tutt, A., additional, Vorobiof, D., additional, Xu, B., additional, Norton, L., additional, and Winer, E., additional

Published
2017
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174. SToRM: A clinical cohort to identify genetic variability related to metastatic phenotypes

Author

Cox, D., primary, Blanc, E., additional, Romieu, G., additional, Rios, M., additional, Becuwe, C., additional, Jouannaud, C., additional, Chaigneau, L., additional, Arnedos, M., additional, Orfeuvre, H., additional, Petit, T., additional, Quenel Tueux, N., additional, Jacquin, J-P., additional, Ferrero, J-M., additional, Abadie Lacourtoisie, S., additional, Penault-Llorca, F., additional, Segura-Ferlay, C., additional, Moullet, I., additional, Bachelot, T., additional, and Pivot, X., additional

Published
2017
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177. Abstract P1-07-02: Chemotherapy (CT) decision in patients (pts) with node-positive (N+), ER+, early breast cancer (EBC) in the wake of new ASCO guideline – A different take on the evidence for the 21-gene recurrence score (RS) assay

Author

Mamounas, E, primary, Goldstein, L, additional, Penault-Llorca, F, additional, Roche, H, additional, Gluz, O, additional, Harbeck, N, additional, Nitz, U, additional, O'Shaughnessy, J, additional, and Albain, K, additional

Published
2017
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178. Abstract P6-09-05: Prognostic and predictive values of high endothelial venules (HEV) and tumor infiltrating CD8+ lymphocytes (CD8) in tumors of patients included in the adjuvant PACS04 trial: HEV is predictive of outcome for HER2+ tumors exposed to trastuzumab

Author

Roché, HH, primary, Lafouresse, FF, additional, Filleron, T, additional, Laffont, R, additional, Maisongrosse, V, additional, Pichery, M, additional, Le Guellec, S, additional, Penault-Llorca, F, additional, Lemonnier, J, additional, Lacroix-Triki, M, additional, and Girard, J-P, additional

Published
2017
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179. Abstract P2-05-04: Evaluation of intra-tumor heterogeneity, test reproducibility and their impact in breast cancer samples assessed by Prosigna™: Results from a decision impact prospective study and a matched case-control study

Author

Rouzier, R, primary, Bonneau, C, additional, Cayre, A, additional, Hequet, D, additional, Gentien, D, additional, Bonhomme, A, additional, Mouret-Reynier, M-A, additional, Dubot, C, additional, Cottu, P, additional, Roulot, A, additional, Morel, P, additional, Salomon, A, additional, Callens, C, additional, Guinebretiere, J-M, additional, and Penault-Llorca, F, additional

Published
2017
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180. Abstract P2-05-10: UCBG 2-14: A prospective multicenter non-randomized trial evaluating the effect of EndoPredict® (EPclin®) clinico-genomic test on treatment decision making among patients with intermediate clinical risk

Author

Penault-Llorca, F, primary, Kwiatkovski, F, additional, Grenier, J, additional, Levy, C, additional, Leheurteur, M, additional, Uwer, L, additional, Derbel, O, additional, Le Rol, A, additional, Jacquin, J-P, additional, Jouannaud, C, additional, Quenel-Tueux, N, additional, Girre, V, additional, Foa, C, additional, Guardiola, E, additional, Lortholary, A, additional, Catala, S, additional, Lemonnier, J, additional, and Delaloge, S, additional

Published
2017
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181. Guidance Statement On BRCA1/2 Tumor Testing in Ovarian Cancer Patients

Author

Capoluongo, E., Ellison, G., Lopez-Guerrero, J.A., Penault-Llorca, F., Ligtenberg, M.J.L., Banerjee, S., Singer, C., Friedman, E., Markiefka, B., Schirmacher, P., Buttner, R., Asperen, C.J. van, Ray-Coquard, I., Endris, V., Kamel-Reid, S., Percival, N., Bryce, J., Rothlisberger, B., Soong, R., Castro, D.G. de, Capoluongo, E., Ellison, G., Lopez-Guerrero, J.A., Penault-Llorca, F., Ligtenberg, M.J.L., Banerjee, S., Singer, C., Friedman, E., Markiefka, B., Schirmacher, P., Buttner, R., Asperen, C.J. van, Ray-Coquard, I., Endris, V., Kamel-Reid, S., Percival, N., Bryce, J., Rothlisberger, B., Soong, R., and Castro, D.G. de

Abstract

Item does not contain fulltext, The approval, in 2015, of the first poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi; olaparib, Lynparza) for platinum-sensitive relapsed high-grade ovarian cancer with either germline or somatic BRCA1/2 deleterious mutations is changing the way that BRCA1/2 testing services are offered to patients with ovarian cancer. Ovarian cancer patients are now being referred for BRCA1/2 genetic testing for treatment decisions, in addition to familial risk estimation, and irrespective of a family history of breast or ovarian cancer. Furthermore, testing of tumor samples to identify the estimated 3%-9% of patients with somatic BRCA1/2 mutations who, in addition to germline carriers, could benefit from PARPi therapy is also now being considered. This new testing paradigm poses some challenges, in particular the technical and analytical difficulties of analyzing chemically challenged DNA derived from formalin-fixed, paraffin-embedded specimens. The current manuscript reviews some of these challenges and technical recommendations to consider when undertaking BRCA1/2 testing in tumor tissue samples to detect both germline and somatic BRCA1/2 mutations. Also provided are considerations for incorporating genetic analysis of ovarian tumor samples into the patient pathway and ethical requirements.

Published
2017

182. 3rd ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 3)' [Breast 31 (February 2017) 244-259]

Author

Cardoso, F., Costa, A., Senkus, E., Aapro, M., Andre, F., Barrios, C.H., Bhattacharyya, G., Biganzoli, L., Cardoso, M.J., Carey, L., Corneliussen-James, D., Curigliano, G., Dieras, V., Saghir, N. El, Eniu, A., Fallowfield, L., Fenech, D., Francis, P., Gelmon, K., Gennari, A., Harbeck, N., Hudis, C., Kaufman, B., Krop, I., Mayer, M., Meijer, H.J.M., Mertz, S., Ohno, S., Pagani, O., Papadopoulos, E., Peccatori, F., Penault-Llorca, F., Piccart, M.J., Pierga, J.Y., Rugo, H., Shockney, L., Sledge, G., Swain, S., Thomssen, C., Tutt, A., Vorobiof, D., Xu, B., Norton, L., Winer, E., Cardoso, F., Costa, A., Senkus, E., Aapro, M., Andre, F., Barrios, C.H., Bhattacharyya, G., Biganzoli, L., Cardoso, M.J., Carey, L., Corneliussen-James, D., Curigliano, G., Dieras, V., Saghir, N. El, Eniu, A., Fallowfield, L., Fenech, D., Francis, P., Gelmon, K., Gennari, A., Harbeck, N., Hudis, C., Kaufman, B., Krop, I., Mayer, M., Meijer, H.J.M., Mertz, S., Ohno, S., Pagani, O., Papadopoulos, E., Peccatori, F., Penault-Llorca, F., Piccart, M.J., Pierga, J.Y., Rugo, H., Shockney, L., Sledge, G., Swain, S., Thomssen, C., Tutt, A., Vorobiof, D., Xu, B., Norton, L., and Winer, E.

Abstract

Item does not contain fulltext

Published
2017

183. Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX

Author

Emile, J, Julie, C, Le Malicot, K, Lepage, C, Tabernero, J, Mini, E, Folprecht, G, Van Laethem, J, Dimet, S, Boulagnon-Rombi, C, Allard, M, Penault-Llorca, F, Bennouna, J, Laurent-Puig, P, Taieb, J, Bidoli, P, Emile, JF, Van Laethem, JL, Allard, MA, Emile, J, Julie, C, Le Malicot, K, Lepage, C, Tabernero, J, Mini, E, Folprecht, G, Van Laethem, J, Dimet, S, Boulagnon-Rombi, C, Allard, M, Penault-Llorca, F, Bennouna, J, Laurent-Puig, P, Taieb, J, Bidoli, P, Emile, JF, Van Laethem, JL, and Allard, MA

Abstract

Background The prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use. Patients and methods According to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study. Primary objective was to compare percentage of patients alive and without recurrence at 2 years in patients with high versus low LI (#NCT02364024). Associations of LI with patient recurrence and survival were analysed, and multivariable models were adjusted for treatment and relevant factors. Automated testing of LI was performed on virtual slides without access to clinical data. Results Among the 1220 CC patients enrolled, LI was high, low and not evaluable in 241 (19.8%), 790 (64.8%) and 189 (15.5%), respectively. Primary objective was met with a 2-year recurrence rate of 14.4% versus 21.1% in patients with high and low LI, respectively (p = 0.02). Patients with high LI also had better disease free survival (DFS) and overall survival (OS). Tumour stage, grade, RAS status and BRAF status were with LI the only prognostic markers in multivariable analysis for OS. Subgroup analyses revealed that high LI had better DFS and OS in mismatch repair (MMR) proficient patients, and in patients without RAS mutation, but not in MMR deficient and RAS mutated patients. Conclusion Although this is the first validation with high level of evidence (IIB) of the prognostic value of a LI test in colon cancers, it still needs to be confirmed in independent series of colon cancer patients. © 2017 Elsevier Ltd

Published
2017

184. Combined cetuximab and trastuzumab are superior to gemcitabine in the treatment of human pancreatic carcinoma xenografts

Author

Larbouret, C., Robert, B., Bascoul-Mollevi, C., Penault-Llorca, F., Ho-Pun-Cheung, A., Morisseau, S., Navarro-Teulon, I., Mach, J.-P, Pèlegrin, A., Azria, D., Larbouret, C., Robert, B., Bascoul-Mollevi, C., Penault-Llorca, F., Ho-Pun-Cheung, A., Morisseau, S., Navarro-Teulon, I., Mach, J.-P, Pèlegrin, A., and Azria, D.

Abstract

Background: Pancreatic carcinoma remains a treatment-refractory cancer with a poor prognosis. Here, we compared anti-epidermal growth factor receptor (EGFR) and anti-HER2 monoclonal antibodies (2mAbs) injections with standard gemcitabine treatment on human pancreatic carcinoma xenografts. Materials and methods: Nude mice, bearing human pancreatic carcinoma xenografts, were treated with either combined anti-EGFR (cetuximab) and anti-HER2 (trastuzumab) or gemcitabine, and tumor growth was observed. Results and conclusion: In first-line therapy, mice survival was significantly longer in the 2mAbs group compared with gemcitabine (P < 0.0001 for BxPC-3, P = 0.0679 for MiaPaCa-2 and P = 0.0019 for Capan-1) and with controls (P < 0.0001). In second-line therapy, tumor regressions were observed after replacing gemcitabine by 2mAbs treatment, resulting in significantly longer animal survival compared with mice receiving continuous gemcitabine injections (P = 0.008 for BxPC-3, P = 0.05 for MiaPaCa-2 and P < 0.001 for Capan-1). Therapeutic benefit of 2mAbs was observed despite K-Ras mutation. Interestingly, concerning the mechanism of action, coinjection of F(ab′)2 fragments from 2mAbs induced significant tumor growth inhibition, compared with controls (P = 0.001), indicating that the 2mAbs had an Fc fragment-independent direct action on tumor cells. This preclinical study demonstrated a significant improvement of survival and tumor regression in mice treated with anti-EGFR/anti-HER2 2mAbs in first- and second-line treatments, compared with gemcitabine, independently of the K-Ras status

Published
2017

185. Guidance Statement On BRCA1/2 Tumor Testing in Ovarian Cancer Patients

Author

Capoluongo, Ettore Domenico, Ellison, G, Lopez-Guerrero, Ja, Penault-Llorca, F, Ligtenberg, Mjl, Banerjee, S, Singer, C, Friedman, E, Markiefka, B, Schirmacher, P, Buttner, R, van Asperen, Cj, Ray-Coquard, I, Endris, V, Kamel-Reid, S, Percival, N, Bryce, J, Rothlisberger, B, Soong, R, de Castro, Dg, Capoluongo, E (ORCID:0000-0001-9872-0572), Capoluongo, Ettore Domenico, Ellison, G, Lopez-Guerrero, Ja, Penault-Llorca, F, Ligtenberg, Mjl, Banerjee, S, Singer, C, Friedman, E, Markiefka, B, Schirmacher, P, Buttner, R, van Asperen, Cj, Ray-Coquard, I, Endris, V, Kamel-Reid, S, Percival, N, Bryce, J, Rothlisberger, B, Soong, R, de Castro, Dg, and Capoluongo, E (ORCID:0000-0001-9872-0572)

Abstract

The approval, in 2015, of the first poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi; olaparib, Lynparza) for platinum sensitive relapsed high grade ovarian cancer with either germline or somatic BRCA1/2 deleterious mutations is changing the way that BRCA1/2 testing services are offered to patients with ovarian cancer. Ovarian cancer patients are now being referred for BRCA1/2 genetic testing for treatment decisions, in addition to familial risk estimation, and irrespective of a family history of breast or ovarian cancer. Furthermore, testing of tumor samples to identify the estimated 3%-9% of patients with somatic BRCA1/2 mutations who, in addition to germline carriers, could benefit from PARPi therapy is also now being considered. This new testing paradigm poses some challenges, in particular the technical and analytical difficulties of analyzing chemically challenged DNA derived from formalin fixed, paraffin embedded specimens. The current manuscript reviews some of these challenges and technical recommendations to consider when undertaking BRCA1/2 testing in tumor tissue samples to detect both germline and somatic BRCA1/2 mutations. Also provided are considerations for incorporating genetic analysis of ovarian tumor samples into the patient pathway and ethical requirements.

Published
2017

188. DNA repair genes implicated in triple negative familial non-BRCA1/2 breast cancer predisposition

Author

Ollier M, Radosevic-Robin N, Kwiatkowski F, Ponelle F, Viala S, Privat M, Uhrhammer N, Bernard-Gallon D, Penault-Llorca F, Yj, Bignon, Yannick Bidet, Equipe de recherche sur les traitements individualisés des cancers (ERTICa), Université d'Auvergne - Clermont-Ferrand I (UdA), service de recherche clinique, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, Laboratoire de diagnostic génétique et moléculaire, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Département d'Oncogénétique, UNICANCER, Service de pathologie, Plateforme GINA, and Université de Clermont

Subjects
pyrosequencing, DNA repair genes, Triple-negative breast cancer, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.CAN]Life Sciences [q-bio]/Cancer, skin and connective tissue diseases, candidate genes, familial non-BRCA1/2 breast cancer, genetic susceptibility
Abstract

International audience; Among breast cancers, 10 to 15% of cases would be due to hereditary risk. In these familial cases, mutations in BRCA1 and BRCA2 are found in only 15% to 20%, meaning that new susceptibility genes remain to be found. Triple-negative breast cancers represent 15% of all breast cancers, and are generally aggressive tumours without targeted therapies available. Our hypothesis is that some patients with triple negative breast cancer could share a genetic susceptibility different from other types of breast cancers. We screened 36 candidate genes, using pyrosequencing, in all the 50 triple negative breast cancer patients with familial history of cancer but no BRCA1 or BRCA2 mutation of a population of 3000 families who had consulted for a familial breast cancer between 2005 and 2013. Any mutations were also sequenced in available relatives of cases. Protein expression and loss of hetero-zygosity were explored in tumours. Seven deleterious mutations in 6 different genes (RAD51D, MRE11A, CHEK2, MLH1, MSH6, PALB2) were observed in one patient each, except the RAD51D mutation found in two cases. Loss of heterozygosity in the tumour was found for 2 of the 7 mutations. Protein expression was absent in tumour tissue for 5 mutations. Taking into consideration a specific subtype of tumour has revealed susceptibility genes, most of them in the homologous recombination DNA repair pathway. This may provide new possibilities for targeted therapies, along with better screening and care of patients.

Published
2015

190. 3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3)

Author

Cardoso, F., primary, Costa, A., additional, Senkus, E., additional, Aapro, M., additional, André, F., additional, Barrios, C.H., additional, Bergh, J., additional, Bhattacharyya, G., additional, Biganzoli, L., additional, Cardoso, M.J., additional, Carey, L., additional, Corneliussen-James, D., additional, Curigliano, G., additional, Dieras, V., additional, El Saghir, N., additional, Eniu, A., additional, Fallowfield, L., additional, Fenech, D., additional, Francis, P., additional, Gelmon, K., additional, Gennari, A., additional, Harbeck, N., additional, Hudis, C., additional, Kaufman, B., additional, Krop, I., additional, Mayer, M., additional, Meijer, H., additional, Mertz, S., additional, Ohno, S., additional, Pagani, O., additional, Papadopoulos, E., additional, Peccatori, F., additional, Penault-Llorca, F., additional, Piccart, M.J., additional, Pierga, J.Y., additional, Rugo, H., additional, Shockney, L., additional, Sledge, G., additional, Swain, S., additional, Thomssen, C., additional, Tutt, A., additional, Vorobiof, D., additional, Xu, B., additional, Norton, L., additional, and Winer, E., additional

Published
2017
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191. Three Rounds of External Quality Assessment in France to Evaluate the Performance of 28 Platforms for Multiparametric Molecular Testing in Metastatic Colorectal and Non-Small Cell Lung Cancer

Author

Dequeker, E.M., Keppens, C., Egele, C., Delen, S., Lamy, A., Lemoine, A., Sabourin, J.C., Andrieu, C., Ligtenberg, M., Fetique, D., Tops, B., Descarpentries, C., Blons, H., Denoux, Y., Aube, C., Penault-Llorca, F., Hofman, P., Leroy, K., Marechal, C. Le, Doucet, L., Duranton-Tanneur, V., Pedeutour, F., Soubeyran, I., Cote, J.F., Emile, J.F., Vignaud, J.M., Monhoven, N., Haddad, V., Laurent-Puig, P., Krieken, H. van, Nowak, F., Lonchamp, E., Bellocq, J.P., Rouleau, E., Dequeker, E.M., Keppens, C., Egele, C., Delen, S., Lamy, A., Lemoine, A., Sabourin, J.C., Andrieu, C., Ligtenberg, M., Fetique, D., Tops, B., Descarpentries, C., Blons, H., Denoux, Y., Aube, C., Penault-Llorca, F., Hofman, P., Leroy, K., Marechal, C. Le, Doucet, L., Duranton-Tanneur, V., Pedeutour, F., Soubeyran, I., Cote, J.F., Emile, J.F., Vignaud, J.M., Monhoven, N., Haddad, V., Laurent-Puig, P., Krieken, H. van, Nowak, F., Lonchamp, E., Bellocq, J.P., and Rouleau, E.

Abstract

Contains fulltext : 171799.pdf (publisher's version ) (Closed access), Personalized medicine has gained increasing importance in clinical oncology, and several clinically important biomarkers are implemented in routine practice. In an effort to guarantee high quality of molecular testing in France, three subsequent external quality assessment rounds were organized at the initiative of the National Cancer Institute between 2012 and 2014. The schemes included clinically relevant biomarkers for metastatic colorectal (KRAS, NRAS, BRAF, PIK3CA, microsatellite instability) and non-small cell lung cancer (EGFR, KRAS, BRAF, PIK3CA, ERBB2), and they represent the first multigene/multicancer studies throughout Europe. In total, 56 laboratories coordinated by 28 regional molecular centers participated in the schemes. Laboratories received formalin-fixed, paraffin-embedded samples and were asked to use routine methods for molecular testing to predict patient response to targeted therapies. They were encouraged to return results within 14 calendar days after sample receipt. Both genotyping and reporting were evaluated separately. During the three external quality assessment rounds, mean genotype scores were all above the preset standard of 90% for all biomarkers. Participants were mainly challenged in case of rare insertions or deletions. Assessment of the written reports showed substantial progress between the external quality assessment schemes on multiple criteria. Several essential elements such as the clinical interpretation of test results and the reason for testing still require improvement by continued external quality assessment education.

Published
2016

194. ERBB2 alterations a new prognostic biomarker in stage III colon cancer from a FOLFOX based adjuvant trial (PETACC8)

Author

Laurent-Puig, P., primary, Balogoun, R., additional, Cayre, A., additional, Le Malicot, K., additional, Tabernero, J., additional, Mini, E., additional, Folprecht, G., additional, van Laethem, J.-L., additional, Thaler, J., additional, Petersen, L. Nørgård, additional, Sanchez, E., additional, Bridgewater, J., additional, Ellis, S., additional, Locher, C., additional, Lagorce, C., additional, Ramé, J.-F., additional, Lepage, C., additional, Penault-Llorca, F., additional, and Taieb, J., additional

Published
2016
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195. Ribociclib plus letrozole in early breast cancer: A presurgical, window-of-opportunity study

Author

Curigliano, G., primary, Gómez Pardo, P., additional, Meric-Bernstam, F., additional, Conte, P., additional, Lolkema, M.P., additional, Beck, J.T., additional, Bardia, A., additional, Martínez García, M., additional, Penault-Llorca, F., additional, Dhuria, S., additional, Tang, Z., additional, Solovieff, N., additional, Miller, M., additional, Di Tomaso, E., additional, and Hurvitz, S.A., additional

Published
2016
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197. Progression-free survival as surrogate end point for overall survival in clinical trials of HER2-targeted agents in HER2-positive metastatic breast cancer

Author

Michiels, S., primary, Pugliano, L., additional, Marguet, S., additional, Grun, D., additional, Barinoff, J., additional, Cameron, D., additional, Cobleigh, M., additional, Di Leo, A., additional, Johnston, S., additional, Gasparini, G., additional, Kaufman, B., additional, Marty, M., additional, Nekljudova, V., additional, Paluch-Shimon, S., additional, Penault-Llorca, F., additional, Slamon, D., additional, Vogel, C., additional, von Minckwitz, G., additional, Buyse, M., additional, and Piccart, M., additional

Published
2016
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198. Medical students faced with related and unrelated living kidney donation: a stratified and multicentre study in Spain

Author

Ríos, A., primary, López-Navas, A., additional, López-López, A., additional, Gómez, F. J., additional, Iriarte, J., additional, Herruzo, R., additional, Blanco, G., additional, Llorca, F. J., additional, Asunsolo, A., additional, Sánchez, P., additional, Gutiérrez, P. R., additional, Fernández, A., additional, de Jesús, M. T., additional, Martínez-Alarcón, L., additional, del Olivo, M., additional, Fuentes, L., additional, Hernández, J. R., additional, Virseda, J., additional, Yelamos, J., additional, Bondía, J. A., additional, Hernández, A., additional, Ayala, M. A., additional, Ramírez, P., additional, and Parrilla, P., additional

Published
2016
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200. Abstract P1-08-06: SToRM: A prospective clinical trial of 1502 metastatic breast cancer (mBC) patients with detail of clinical presentation, molecular subtype, treatment modalities, prognosis and GWAS genotyping

Author

Bachelot, T, primary, Lavergne, E, additional, Romieu, G, additional, Rios, M, additional, Heudel, P-E, additional, Roemer-Becuwe, C, additional, Jouannaud, C, additional, Tredan, O, additional, Chaigneau, L, additional, Arnedos, M, additional, Orfeuvre, H, additional, Petit, T, additional, Quenel-Tueux, N, additional, Jacquin, J-P, additional, Ferrero, J-M, additional, Moullet, I, additional, Abadie-Lacourtoisie, S, additional, Penault-Llorca, F, additional, Blanc, E, additional, and Cox, D, additional

Published
2016
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